Trial Outcomes & Findings for A Study of Management of Tarceva - Induced Rash in Patients With Non-Small Cell Lung Cancer. (NCT NCT00531934)
NCT ID: NCT00531934
Last Updated: 2015-02-25
Results Overview
Description of skin rash (folliculitis, including erythema, papulo-pustules, nodule, and crust) was according to Common Terminology Criteria for Adverse Events (CTCAE) version 3 scale. Medical pictures of the face (front and sides views) systematically, and of any region presenting with skin lesions were obtained. The pictures were reviewed by a centralized committee of evaluation.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
147 participants
Primary outcome timeframe
Days 0, 14, 28 and Months 2, 3, and 4
Results posted on
2015-02-25
Participant Flow
Participant milestones
| Measure |
Erlotinib Plus (+) Doxycycline
Participants received erlotinib 150 milligrams per day (mg/day), tablets, orally (PO) until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Overall Study
STARTED
|
73
|
74
|
|
Overall Study
COMPLETED
|
7
|
11
|
|
Overall Study
NOT COMPLETED
|
66
|
63
|
Reasons for withdrawal
| Measure |
Erlotinib Plus (+) Doxycycline
Participants received erlotinib 150 milligrams per day (mg/day), tablets, orally (PO) until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
8
|
|
Overall Study
Progression
|
52
|
42
|
|
Overall Study
Death
|
7
|
10
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Other
|
2
|
2
|
Baseline Characteristics
A Study of Management of Tarceva - Induced Rash in Patients With Non-Small Cell Lung Cancer.
Baseline characteristics by cohort
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
Total
n=147 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.5 years
STANDARD_DEVIATION 10.6 • n=99 Participants
|
64.2 years
STANDARD_DEVIATION 11.1 • n=107 Participants
|
63.8 years
STANDARD_DEVIATION 10.8 • n=206 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=99 Participants
|
24 Participants
n=107 Participants
|
49 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=99 Participants
|
50 Participants
n=107 Participants
|
98 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, and 4Population: ITT population; data for 1 participant in the erlotinib treatment group were missing.
Description of skin rash (folliculitis, including erythema, papulo-pustules, nodule, and crust) was according to Common Terminology Criteria for Adverse Events (CTCAE) version 3 scale. Medical pictures of the face (front and sides views) systematically, and of any region presenting with skin lesions were obtained. The pictures were reviewed by a centralized committee of evaluation.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade During the First 4 Months of Treatment
|
71.2 percentage of participants
|
80.8 percentage of participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, and 4Population: ITT population
A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustular and nodules.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Number of Skin Rash (Folliculitis) Events During the First 4 Months of Treatment
|
57 rash events
|
62 rash events
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, and 4Population: ITT population
A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustule, nodule, and crust.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type
Erythema
|
55.8 percentage of participants
|
70.7 percentage of participants
|
|
Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type
Papulo-pustule
|
65.4 percentage of participants
|
72.4 percentage of participants
|
|
Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type
Nodule
|
1.9 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type
Crust
|
9.6 percentage of participants
|
25.9 percentage of participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, and 4Population: ITT population; only participants with an adverse event of skin rash (folliculitis) during the first 4 months were included in the analysis.
Intensity of skin rashes was classified according to CTCAE grading. Grade 1 equals (=) Macular or papular eruption or erythema without associated symptoms; Grade 2=Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering less than (\<)50 percent (%) of body surface area (BSA); Grade 3=Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=52 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=59 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Maximal Intensity
Grade 1
|
61.5 percentage of participants
|
18.6 percentage of participants
|
|
Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Maximal Intensity
Grade 2
|
34.6 percentage of participants
|
62.7 percentage of participants
|
|
Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Maximal Intensity
Grade 3
|
3.8 percentage of participants
|
18.6 percentage of participants
|
SECONDARY outcome
Timeframe: Months 7, 10, and 12Population: ITT population
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade After the First 4 Months of Treatment
|
2.7 percentage of participants
|
1.4 percentage of participants
|
SECONDARY outcome
Timeframe: Months 7, 10, and 12Population: ITT population
A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustular and nodules.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Number of Skin Rash (Folliculitis) Events After the First 4 Months of Treatment
|
2 rash events
|
1 rash events
|
SECONDARY outcome
Timeframe: Months 7, 10, and 12Population: ITT population
A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustule, nodule, and crust.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type
Papulo-pustule
|
1 participants
|
1 participants
|
|
Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type
Erythema
|
1 participants
|
1 participants
|
|
Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type
Nodule
|
0 participants
|
0 participants
|
|
Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type
Crust
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Months 7, 10, and 12Population: ITT population
Intensity of skin rashes was classified according to CTCAE grading. Grade 1=Macular or papular eruption or erythema without associated symptoms; Grade 2=Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering \<50% of BSA; Grade 3=Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Intensity
Initial intensity: Grade 1
|
2 participants
|
1 participants
|
|
Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Intensity
Maximal intensity: Grade 1
|
2 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, and 4Population: ITT population
Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Number of Participants With an Event
|
52 participants
|
59 participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, and 4Population: ITT population
Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Time to Event
|
14 days
Interval 13.0 to 22.0
|
13 days
Interval 8.0 to 16.0
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, and 4Population: ITT population
Percentage of participants estimated to be without skin rash (folliculitis) at 4 months.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants Estimated to be Event Free at 4 Months
|
24.7 percentage of participants
|
11.2 percentage of participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12Population: ITT population
Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Number of Participants With an Event
|
53 participants
|
59 participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12Population: ITT population
Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Time to Event
|
14 days
Interval 13.0 to 22.0
|
13 days
Interval 8.0 to 16.0
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12Population: ITT population
Percentage of participants estimated to be without skin rash (folliculitis) at 12 months.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants Estimated to be Event Free at 12 Months
|
19.8 percentage of participants
|
11.2 percentage of participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, and 4Population: ITT Population; only participants with an event (folliculitis) were included in the analysis.
If the cutaneous rash was ongoing at the last visit or Month 4, the duration of cutaneous rash was calculated between start of folliculitis and Visit Month 4 or premature withdrawal visit or death.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=57 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=61 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Duration of Skin Rash (Folliculitis) During the First 4 Months of Treatment
|
59.6 days
Standard Deviation 35.9
|
60.6 days
Standard Deviation 33.5
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12Population: ITT Population; only participants with an event (folliculitis) were included in the analysis.
If the end of cutaneous rash was missing, the duration of cutaneous rash was calculated between start of folliculitis and last evaluation date.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=59 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=62 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Duration of Skin Rash (Folliculitis) During the Whole Treatment Period
|
86.7 days
Standard Deviation 81.1
|
99.3 days
Standard Deviation 90.5
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, and 4Population: ITT population
Other skin lesions included presence or absence of xerosis and paronychia.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants With Other Skin Lesions of Any Grade During the First 4 Months of Treatment
|
39.7 percentage of participants
|
42.5 percentage of participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, and 4Population: ITT population
Other skin lesions included xerosis and paronychia.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Type
Xerosis
|
37.0 percentage of participants
|
41.1 percentage of participants
|
|
Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Type
Paronychia
|
6.8 percentage of participants
|
8.2 percentage of participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, and 4Population: ITT population; only participants with an adverse event classified as other skin lesion during the first 4 months were included in the analysis.
Other skin lesions included xerosis and paronychia. Intensity was classified according to CTCAE grading. Grade 1=Macular or papular eruption or erythema without associated symptoms; Grade 2=Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering \<50% of BSA; Grade 3=Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation; Grade 4=Generalized exfoliative, ulcerative, or bullous dermatitis. If a participant had several skin lesions, the maximal intensity was taken into account.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=29 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=31 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity
Grade 1
|
69.0 percentage of participants
|
29.0 percentage of participants
|
|
Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity
Grade 2
|
24.1 percentage of participants
|
51.6 percentage of participants
|
|
Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity
Grade 3
|
6.9 percentage of participants
|
16.1 percentage of participants
|
|
Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity
Grade 4
|
0 percentage of participants
|
3.2 percentage of participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12Population: ITT population; only participants that discontinued or interrupted erlotinib were included in the analysis.
Erlotinib dose adjustment was done in case of toxicity occurrence. Keratitis, diarrhea, interstitial lung disease, and other toxic occurrences determined erlotinib dose reduction. If erlotinib was previously discontinued for skin rash or diarrhea of Grade 2 and if these symptoms of Grade 2 recurred OR if the symptoms were intolerable for the participants, erlotinib was discontinued until recovery/Grade 1 then the dose was reduced of one level of 50 mg.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=23 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=32 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants With Erlotinib Dose Reduction by Reason for Reduction
Adverse event
|
80.0 percentage of participants
|
85.7 percentage of participants
|
|
Percentage of Participants With Erlotinib Dose Reduction by Reason for Reduction
Investigator's decision
|
0 percentage of participants
|
2.4 percentage of participants
|
|
Percentage of Participants With Erlotinib Dose Reduction by Reason for Reduction
Other
|
20.0 percentage of participants
|
11.9 percentage of participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12Population: ITT population; only participants that discontinued or interrupted doxycycline were included in the analysis.
Occurrence of folliculitis-type skin rash of Grade greater than or equal to (≥)2 led to dose modification. Continuation of treatment with doxycycline after occurrence of folliculitis-type skin rash of Grade ≥2 was upon the investigator's opinion.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=8 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants With Doxycycline Dose Reduction by Reason for Reduction
Adverse event
|
50.0 percentage of participants
|
—
|
|
Percentage of Participants With Doxycycline Dose Reduction by Reason for Reduction
Other
|
50.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Months 2, 4, 7, 10, and 12Population: ITT population; number (n) = number of participants analyzed for the specified parameter at a given visit.
Disease control was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for evaluation and was defined as participants with either complete response (CR), partial response (PR), or stable disease (SD).
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=34 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=33 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants With Global Disease Control by Visit
Month 2 (n=34,33)
|
88.2 percentage of participants
|
93.9 percentage of participants
|
|
Percentage of Participants With Global Disease Control by Visit
Month 4 (n=19,25)
|
89.5 percentage of participants
|
80.0 percentage of participants
|
|
Percentage of Participants With Global Disease Control by Visit
Month 7 (n=11,17)
|
72.7 percentage of participants
|
76.5 percentage of participants
|
|
Percentage of Participants With Global Disease Control by Visit
Month 10 (n=7,12)
|
100.0 percentage of participants
|
66.7 percentage of participants
|
|
Percentage of Participants With Global Disease Control by Visit
Month 12 (n=7,10)
|
71.4 percentage of participants
|
40.0 percentage of participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12Population: ITT Population
Response was determined according to the RECIST criteria for evaluation and was defined as participants with either CR, PR, SD, or progression. No CR was reported.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=58 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=58 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants by Best Global Response Under Treatment
PR
|
15.5 percentage of participants
|
10.3 percentage of participants
|
|
Percentage of Participants by Best Global Response Under Treatment
SD
|
36.2 percentage of participants
|
48.3 percentage of participants
|
|
Percentage of Participants by Best Global Response Under Treatment
Progression
|
48.3 percentage of participants
|
41.4 percentage of participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12Population: ITT Population
PFS was defined by the time between first intake of treatment with erlotinib and disease progression or death for any cause; estimated using Kaplan-Meier method.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Progression-Free Survival (PFS) - Percentage of Participants With an Event
|
91.8 percentage of participants
|
87.8 percentage of participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12Population: ITT Population
PFS was defined by the time between first intake of treatment with erlotinib and disease progression or death for any cause; estimated using Kaplan-Meier method.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Progression-Free Survival (PFS) - Time to Event
|
63.0 days
Interval 56.0 to 107.0
|
70.0 days
Interval 56.0 to 107.0
|
SECONDARY outcome
Timeframe: Months 4 and 12Population: ITT Population
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants Estimated to be Progression Free at 4 and 12 Months
4 Months
|
30.1 percentage of participants
|
31.0 percentage of participants
|
|
Percentage of Participants Estimated to be Progression Free at 4 and 12 Months
12 Months
|
6.3 percentage of participants
|
10.8 percentage of participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12Population: ITT Population
OS was defined by the time between first intake of treatment with erlotinib and death for any cause; analyzed using Kaplan-Meier method.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Overall Survival (OS) - Percentage of Participants With an Event
|
71.2 percentage of participants
|
67.6 percentage of participants
|
SECONDARY outcome
Timeframe: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12Population: ITT Population
OS was defined by the time between first intake of treatment with erlotinib and death for any cause; analyzed using Kaplan-Meier method.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Overall Survival (OS) - Time to Event
|
227.0 days
Interval 153.0 to 282.0
|
251.0 days
Interval 152.0 to 336.0
|
SECONDARY outcome
Timeframe: Months 4 and 12Population: ITT Population
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=73 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants Estimated to be Alive at 4 and 12 Months
4 Months
|
68.5 percentage of participants
|
69.7 percentage of participants
|
|
Percentage of Participants Estimated to be Alive at 4 and 12 Months
12 Months
|
27.1 percentage of participants
|
33.5 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Days 14 and 28 and Months 2, 3, and 4Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
Quality of life was assessed by participant's responses to a DLQI questionnaire. The DLQI is a 10-item questionnaire assessing quality of life; questions were assessed on a 4-point scale (0=not at all; 1=a little; 2=a lot; and 3=very much). The DLQI was calculated by summing the score of each question resulting in a maximum of 30 (extremely large effect on participant's life) and a minimum of 0 (no effect at all on participant's life). The higher the score, the more quality of life is impaired. Analysis was performed by visit well as at the last available value after baseline (Endpoint); change from baseline to endpoint was also determined.
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=67 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=69 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Dermatology Life Quality Index (DLQI) Global Score
Baseline (n=67,69)
|
0.2 units on a scale
Standard Deviation 0.5
|
0.2 units on a scale
Standard Deviation 0.6
|
|
Dermatology Life Quality Index (DLQI) Global Score
Day 14 (n=63,62)
|
1.7 units on a scale
Standard Deviation 3.2
|
3.7 units on a scale
Standard Deviation 4.3
|
|
Dermatology Life Quality Index (DLQI) Global Score
Day 28 (n=60,56)
|
1.7 units on a scale
Standard Deviation 2.5
|
3.4 units on a scale
Standard Deviation 4.0
|
|
Dermatology Life Quality Index (DLQI) Global Score
Month 2 (n=35,37)
|
2.3 units on a scale
Standard Deviation 4.1
|
4.3 units on a scale
Standard Deviation 5.3
|
|
Dermatology Life Quality Index (DLQI) Global Score
Month 3 (n=29,27)
|
1.7 units on a scale
Standard Deviation 2.7
|
3.2 units on a scale
Standard Deviation 3.7
|
|
Dermatology Life Quality Index (DLQI) Global Score
Month 4 (n=19,24)
|
1.6 units on a scale
Standard Deviation 3.0
|
2.6 units on a scale
Standard Deviation 3.5
|
|
Dermatology Life Quality Index (DLQI) Global Score
Endpoint (n=65,63)
|
2.0 units on a scale
Standard Deviation 3.3
|
3.4 units on a scale
Standard Deviation 4.8
|
|
Dermatology Life Quality Index (DLQI) Global Score
Change at Endpoint (n=35,37)
|
1.9 units on a scale
Standard Deviation 3.3
|
3.2 units on a scale
Standard Deviation 4.8
|
SECONDARY outcome
Timeframe: Baseline, Days 14 and 28 and Months 2, 3, and 4Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
Quality of life was assessed by participant's responses to a DLQI questionnaire. The DLQI is a 10-item questionnaire assessing quality of life; questions were assessed on a 4-point scale (0=not at all; 1=a little; 2=a lot; and 3=very much). The DLQI was calculated by summing the score of each question resulting in a maximum of 30 (extremely large effect on participant's life) and a minimum of 0 (no effect at all on participant's life). The higher the score, the more quality of life is impaired. The DLQI global score was classified into 5 levels: 0-1 (no effect at all), 2-5 (small effect), 6-10 (moderate effect), 11-20 (very large effect) and 21-30 (extremely large effect).
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=67 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=69 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Baseline, no effect (n=67,69)
|
98.5 percentage of participants
0.5
|
97.1 percentage of participants
0.6
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Baseline, small effect (n=67,69)
|
1.5 percentage of participants
3.2
|
2.9 percentage of participants
4.3
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Day 14, no effect (n=63,62)
|
69.8 percentage of participants
2.5
|
41.9 percentage of participants
4.0
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Day 14, small effect (n=63,62)
|
27.0 percentage of participants
3.3
|
30.6 percentage of participants
4.8
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Day 14, moderate effect (n=63,62)
|
0.0 percentage of participants
4.1
|
21.0 percentage of participants
5.3
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Day 14, very large effect (n=63,62)
|
1.6 percentage of participants
2.7
|
6.5 percentage of participants
3.7
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Day 14, extremely large effect (n=63,62)
|
1.6 percentage of participants
3.0
|
0.0 percentage of participants
3.5
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Day 28, no effect (n=60,56)
|
66.7 percentage of participants
|
41.1 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Day 28, small effect (n=60,56)
|
25.0 percentage of participants
|
35.7 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Day 28, moderate effect (n=60,56)
|
8.3 percentage of participants
|
19.6 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Day 28, very large effect (n=60,56)
|
0.0 percentage of participants
|
1.8 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Day 28, extremely large effect (n=60,56)
|
0.0 percentage of participants
|
1.8 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Month 2, no effect (n=35,37)
|
65.7 percentage of participants
|
40.5 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Month 2, small effect (n=35,37)
|
22.9 percentage of participants
|
27.0 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Month 2, moderate effect (n=35,37)
|
5.7 percentage of participants
|
21.6 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Month 2, very large effect (n=35,37)
|
5.7 percentage of participants
|
8.1 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Month 2, extremely large effect (n=35,37)
|
0.0 percentage of participants
|
2.7 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Month 3, no effect (n=29,27)
|
69.0 percentage of participants
|
37.0 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Month 3, small effect (n=29,27)
|
27.6 percentage of participants
|
44.4 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Month 3, moderate effect (n=29,27)
|
0.0 percentage of participants
|
11.1 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Month 3, very large effect (n=29,27)
|
3.4 percentage of participants
|
7.4 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Month 4, no effect (n=19,24)
|
78.9 percentage of participants
|
50.0 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Month 4, small effect (n=19,24)
|
15.8 percentage of participants
|
41.7 percentage of participants
|
|
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Month 4, very large effect (n=19,24)
|
5.3 percentage of participants
|
8.3 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Days 14 and 28, and Months 2, 3, and 4Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
Quality of life was assessed by participant's responses to a VAS questionnaire - (evaluation of satisfaction with skin status). VAS was measured on a 100 millimeter (mm) scale where 0 = not at all satisfied and 100 = very satisfied. Participants were asked to mark the line corresponding to their satisfaction at each visit and the distance from the left edge was measured. A negative change from baseline indicates improvement. Analysis was performed by visit well as at the last available value after baseline (Endpoint).
Outcome measures
| Measure |
Erlotinib + Doxycycline
n=64 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=68 Participants
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Quality of Life Score as Assessed by Visual Analog Scale (VAS)
Month 3 (n=28,27)
|
63.5 mm
Standard Deviation 21.4
|
56.1 mm
Standard Deviation 31.7
|
|
Quality of Life Score as Assessed by Visual Analog Scale (VAS)
Month 4 (n=18,24)
|
71.8 mm
Standard Deviation 20.9
|
59.9 mm
Standard Deviation 29.7
|
|
Quality of Life Score as Assessed by Visual Analog Scale (VAS)
Endpoint (n=65,64)
|
64.0 mm
Standard Deviation 26.6
|
58.3 mm
Standard Deviation 30.8
|
|
Quality of Life Score as Assessed by Visual Analog Scale (VAS)
Change at Endpoint (n=60,62)
|
-18.1 mm
Standard Deviation 27.7
|
-30.4 mm
Standard Deviation 31.4
|
|
Quality of Life Score as Assessed by Visual Analog Scale (VAS)
Baseline (n=64,68)
|
81.4 mm
Standard Deviation 23.7
|
87.8 mm
Standard Deviation 19.6
|
|
Quality of Life Score as Assessed by Visual Analog Scale (VAS)
Day 14 (n=62,63)
|
68.8 mm
Standard Deviation 26.6
|
51.0 mm
Standard Deviation 34.5
|
|
Quality of Life Score as Assessed by Visual Analog Scale (VAS)
Change at Day 14 (n=59,61)
|
-16.2 mm
Standard Deviation 28.5
|
-39.2 mm
Standard Deviation 37.8
|
|
Quality of Life Score as Assessed by Visual Analog Scale (VAS)
Day 28 (n=59,56)
|
66.5 mm
Standard Deviation 27.2
|
54.8 mm
Standard Deviation 27.0
|
|
Quality of Life Score as Assessed by Visual Analog Scale (VAS)
Change at Day 28 (n=55,54)
|
-15.5 mm
Standard Deviation 28.8
|
-35.1 mm
Standard Deviation 27.8
|
|
Quality of Life Score as Assessed by Visual Analog Scale (VAS)
Month 2 (n=36,36)
|
68.9 mm
Standard Deviation 22.8
|
52.6 mm
Standard Deviation 27.4
|
Adverse Events
Erlotinib + Doxycycline
Serious events: 18 serious events
Other events: 71 other events
Deaths: 0 deaths
Erlotinib
Serious events: 24 serious events
Other events: 69 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Erlotinib + Doxycycline
n=73 participants at risk
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 participants at risk
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Cardiac disorders
Myocardial infarction
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Abdominal pain
|
2.7%
2/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Colonic obstruction
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Diarrhoea
|
2.7%
2/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Staphylococcal skin infection
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Cardiac disorders
Pericarditis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
General physical health deterioration
|
5.5%
4/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
8.1%
6/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Cardiac disorders
Myocardial ischaemia
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Intracranial pressure increased
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Cardiac disorders
Cardiac failure
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Death
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Malaise
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Sepsis
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
5.4%
4/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Chest pain
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Skin and subcutaneous tissue disorders
Folliculitis
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Pain
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Xerosis
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Vascular disorders
Phlebitis
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
4.1%
3/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Headache
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Oesophageal achalasia
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Sciatica
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
Other adverse events
| Measure |
Erlotinib + Doxycycline
n=73 participants at risk
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.
|
Erlotinib
n=74 participants at risk
Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Folliculitis
|
72.6%
53/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
78.4%
58/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Skin and subcutaneous tissue disorders
Paronychia
|
6.8%
5/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
8.1%
6/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
2.7%
2/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
4.1%
3/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Skin and subcutaneous tissue disorders
Hypertrichosis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Skin and subcutaneous tissue disorders
Intertrigo
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Skin and subcutaneous tissue disorders
Ingrowing nail
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Diarrhoea
|
35.6%
26/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
45.9%
34/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Vomiting
|
13.7%
10/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
10.8%
8/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Nausea
|
11.0%
8/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
10.8%
8/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Constipation
|
11.0%
8/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
6.8%
5/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Abdominal pain
|
6.8%
5/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Stomatitis
|
11.0%
8/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
2.7%
2/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
4.1%
3/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
4.1%
3/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
5.5%
4/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
4.1%
3/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Haemorrhoids
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Abdominal rigidity
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Aerophagia
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Dry mouth
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Dyspepsia
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Dysphagia
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Faecaloma
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Gingival hypertrophy
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Gingival pain
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Gingivitis
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Glossitis
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Hiatus hernia
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Gastrointestinal disorders
Subileus
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Xerosis
|
38.4%
28/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
40.5%
30/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Asthenia
|
6.8%
5/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
12.2%
9/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
General physical health deterioration
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
5.4%
4/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Oedema peripheral
|
4.1%
3/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Chest pain
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Pain
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Fatigue
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Malaise
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Pyrexia
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Catheter site inflammation
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
General disorders
Hyperthermia
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Bronchitis
|
2.7%
2/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Fungal skin infection
|
2.7%
2/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Oral fungal infection
|
4.1%
3/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Gastroenteritis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Lung infection
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Staphylococcal infection
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Abscess
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Bronchitis viral
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Bronchopulmonary aspergillosis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Central line infection
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Conjunctivitis infective
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Cystitis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Ear infection
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Fungal infection
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Herpes zoster
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Influenza
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Nasopharyngitis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Oral herpes
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Pertussis
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Sinusitis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Tonsillitis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Infections and infestations
Vaginal infection
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Eye disorders
Conjunctivitis
|
2.7%
2/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
8.1%
6/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Eye disorders
Dry eye
|
2.7%
2/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Eye disorders
Eye pruritus
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Eye disorders
Growth of eyelashes
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Eye disorders
Eye irritation
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Eye disorders
Eye pain
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Eye disorders
Keratitis
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Eye disorders
Lacrimation increased
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Eye disorders
Visual distrubance
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.1%
3/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.7%
2/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
2.7%
2/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
5.4%
4/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal disorder
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Metabolism and nutrition disorders
Anorexia
|
6.8%
5/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
12.2%
9/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
4.1%
3/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Headache
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
4.1%
3/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Sciatica
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Transient ischaemic attack
|
2.7%
2/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Aphonia
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Dementia
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Dysgeusia
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Epiduritis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Facial neuralgia
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Parosmia
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Syncope
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Nervous system disorders
Vocal cord paralysis
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Investigations
Weight decreased
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
5.4%
4/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Investigations
Blood bilirubin increased
|
5.5%
4/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Investigations
Liver function test abnormal
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Investigations
White blood cell count increased
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Blood and lymphatic system disorders
Anaemia
|
5.5%
4/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
6.8%
5/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Psychiatric disorders
Depression
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
4.1%
3/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Psychiatric disorders
Insomnia
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Vascular disorders
Phlebitis
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Vascular disorders
Deep vein thrombosis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Vascular disorders
Haematoma
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Vascular disorders
Hypotension
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Vascular disorders
Periphlebitis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Vascular disorders
Venous thrombosis limb
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Cardiac disorders
Tachycardia
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Cardiac disorders
Cardiac tamponade
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Hepatobiliary disorders
Cytolytic hepatitis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
4.1%
3/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Hepatobiliary disorders
Cholestasis
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Injury, poisoning and procedural complications
Eschar
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
2.7%
2/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Injury, poisoning and procedural complications
Traumatic haematoma
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Ear and labyrinth disorders
Vertigo
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Ear and labyrinth disorders
Cerumen impaction
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Ear and labyrinth disorders
Ear haemorrhage
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Renal and urinary disorders
Renal failure
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Endocrine disorders
Adrenal insufficiency
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
1.4%
1/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
0.00%
0/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
|
Reproductive system and breast disorders
Vulvovaginal dryness
|
0.00%
0/73 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
1.4%
1/74 • Adverse events (AEs) were recorded continuously until 30 days after the last treatment administration.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER