Trial Outcomes & Findings for Cisplatin and Etoposide Versus Temozolomide and Capecitabine in Patients With Advanced Poorly Differentiated (G3) Non-Small Cell Gastrointestinal Neuroendocrine Carcinomas (NCT NCT02595424)

Last Updated: 2026-05-01

Results Overview

PFS is defined as the time from randomization to documented progression or death without progression. PFS is censored at the date of last disease evaluation. The study was closed for futility in 2021 after the 2021 Spring DSMC meeting, which found that the boundary for futility had been met (ie, temozolomide and capecitabine did not appear to be superior to platinum and etoposide chemotherapy). As the interim analysis finding led to the conclusion of the study, no PFS stratified logrank test was conducted with the data extracted on April 23rd, 2025 for the final analysis, that was presented here.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

assessed at baseline, every 8 weeks until treatment completion, then every 3 months within 2 years and every 6 months within 3-5 years from randomization until disease progression, up to 5 years from study registration

Results posted on

2026-05-01

Participant Flow

The study was activated on November 6th, 2015 and closed to accrual on April 1st, 2021 with final accrual of 67 patients.

Participant milestones

Participant milestones
Measure	Arm A (Capecitabine, Temozolomide) Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO	Arm B (Cisplatin, Carboplatin, Etoposide) Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Cisplatin: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies
Overall Study STARTED	32	35
Overall Study Eligible	31	32
Overall Study Started protocol therapy	28	29
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	32	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Capecitabine, Temozolomide) Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO	Arm B (Cisplatin, Carboplatin, Etoposide) Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Cisplatin: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies
Overall Study Disease progression	17	15
Overall Study Adverse Event	5	7
Overall Study Withdrawal by Subject	2	5
Overall Study Physician Decision	1	2
Overall Study Death	1	0
Overall Study Alternative therapy	2	0
Overall Study Never start protocol therapy	4	6

Baseline Characteristics

Cisplatin and Etoposide Versus Temozolomide and Capecitabine in Patients With Advanced Poorly Differentiated (G3) Non-Small Cell Gastrointestinal Neuroendocrine Carcinomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Capecitabine, Temozolomide) n=31 Participants Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO	Arm B (Cisplatin, Carboplatin, Etoposide) n=32 Participants Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Cisplatin: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies	Total n=63 Participants Total of all reporting groups
Age, Continuous	66 years n=14 Participants	62 years n=34 Participants	65 years n=69 Participants
Sex: Female, Male Female	11 Participants n=14 Participants	14 Participants n=34 Participants	25 Participants n=69 Participants
Sex: Female, Male Male	20 Participants n=14 Participants	18 Participants n=34 Participants	38 Participants n=69 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=14 Participants	1 Participants n=34 Participants	1 Participants n=69 Participants
Race (NIH/OMB) Asian	0 Participants n=14 Participants	1 Participants n=34 Participants	1 Participants n=69 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=14 Participants	1 Participants n=34 Participants	1 Participants n=69 Participants
Race (NIH/OMB) Black or African American	1 Participants n=14 Participants	2 Participants n=34 Participants	3 Participants n=69 Participants
Race (NIH/OMB) White	27 Participants n=14 Participants	26 Participants n=34 Participants	53 Participants n=69 Participants
Race (NIH/OMB) More than one race	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=14 Participants	1 Participants n=34 Participants	4 Participants n=69 Participants

PRIMARY outcome

Timeframe: assessed at baseline, every 8 weeks until treatment completion, then every 3 months within 2 years and every 6 months within 3-5 years from randomization until disease progression, up to 5 years from study registration

Population: All eligible patients

Outcome measures

Outcome measures
Measure	Arm A (Capecitabine, Temozolomide) -- Ki-67 Low n=31 Participants Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO	Arm B (Cisplatin, Carboplatin, Etoposide)--- Ki-67 Low n=32 Participants Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Cisplatin: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm A (Capecitabine, Temozolomide) -- Ki-67 High Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO	Arm B (Cisplatin, Carboplatin, Etoposide)--- Ki-67 High Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Cisplatin: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studie
Progression-free Survival (PFS)	3.1 months Interval 2.1 to 8.4	5.5 months Interval 4.0 to 8.0	—	—

SECONDARY outcome

Timeframe: assessed at baseline, then every 3 months within 2 years from randomization, and every 6 months if patient is 3-5 years from randomization, up to 5 years from randomization

Population: All eligible patients

OS is defined as the time from randomization to death from any cause. OS is censored at the date of last contact. Median OS is estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Arm A (Capecitabine, Temozolomide) -- Ki-67 Low n=31 Participants Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO	Arm B (Cisplatin, Carboplatin, Etoposide)--- Ki-67 Low n=32 Participants Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Cisplatin: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm A (Capecitabine, Temozolomide) -- Ki-67 High Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO	Arm B (Cisplatin, Carboplatin, Etoposide)--- Ki-67 High Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Cisplatin: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studie
Overall Survival (OS)	12.6 months Interval 5.4 to 30.3	10.8 months Interval 9.6 to 21.1	—	—

SECONDARY outcome

Timeframe: assessed at baseline, every 8 weeks until treatment completion, then every 3 months within 2 years and every 6 months within 3-5 years, up to 5 years from registration; the best response among all assessments was considered as objective response

Population: All eligible patients

ORR is defined as the proportion of patients with complete response (CR) or partial response (PR). Response is evaluated using the RECIST 1.1 criteria. CR is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Arm A (Capecitabine, Temozolomide) -- Ki-67 Low n=31 Participants Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO	Arm B (Cisplatin, Carboplatin, Etoposide)--- Ki-67 Low n=32 Participants Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Cisplatin: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm A (Capecitabine, Temozolomide) -- Ki-67 High Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO	Arm B (Cisplatin, Carboplatin, Etoposide)--- Ki-67 High Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Cisplatin: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studie
Objective Response Rate (ORR)	19 percentage of participants Interval 7.0 to 37.0	31 percentage of participants Interval 16.0 to 50.0	—	—

OTHER_PRE_SPECIFIED outcome

Population: Eligible patients with Ki-67 data

The impact of each treatment regimen on objective response rate (ORR, defined as above in the secondary objective) are assessed by Ki-67 index level as an exploratory analysis. Using Youden's index, which considers specificity and sensitivity equally important, the optimal cutoff point of Ki-67 index to best predict response is 50.5. Using the optimal Ki-67 cutoff value of 50.5 from the ROC analysis, patients were divided into Ki-67 low (Ki-67 \< 50.5) and high (Ki-67 ≥ 50.5) groups. The impact of each treatment regimen on ORR was explored in Ki-67 low and Ki-67 high separately.

Outcome measures

Outcome measures
Measure	Arm A (Capecitabine, Temozolomide) -- Ki-67 Low n=20 Participants Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO	Arm B (Cisplatin, Carboplatin, Etoposide)--- Ki-67 Low n=14 Participants Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Cisplatin: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm A (Capecitabine, Temozolomide) -- Ki-67 High n=11 Participants Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO	Arm B (Cisplatin, Carboplatin, Etoposide)--- Ki-67 High n=18 Participants Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Cisplatin: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studie
To Assess the Objective Response Rate Based on Marker of Proliferation Ki-67 Index	25.0 percentage of participants Interval 8.7 to 49.1	35.7 percentage of participants Interval 12.8 to 64.9	9.1 percentage of participants Interval 0.2 to 41.3	27.8 percentage of participants Interval 9.7 to 53.5

OTHER_PRE_SPECIFIED outcome

The impact of each treatment regimen on PFS and OS (defined as above in the primary and secondary objectives) are assessed by Ki-67 index level as an exploratory analysis. Using Youden's index, which considers specificity and sensitivity equally important, the optimal cutoff point of Ki-67 index to best predict response is 50.5. Using the optimal Ki-67 cutoff value of 50.5 from the ROC analysis, patients were divided into Ki-67 low (Ki-67 \< 50.5) and high (Ki-67 ≥ 50.5) groups. The impact of each treatment regimen on PFS and OS were explored in Ki-67 low and Ki-67 high separately.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

The association between tumor differentiation (well differentiated versus poorly differentiated) with PFS, ORR and OS (defined as in the primary and secondary objectives) were evaluated.

Outcome measures

Outcome data not reported

Adverse Events

Arm A (Capecitabine, Temozolomide)

Serious events: 9 serious events

Other events: 27 other events

Deaths: 23 deaths

Arm B (Cisplatin, Carboplatin, Etoposide)

Serious events: 20 serious events

Other events: 28 other events

Deaths: 25 deaths

Serious adverse events

Other adverse events

Additional Information

Study Statistician

ECOG-ACRIN Statistical Office

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm A (Capecitabine, Temozolomide) n=28 participants at risk Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Cisplatin, Carboplatin, Etoposide) n=29 participants at risk Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
General disorders and administration site conditions Fatigue	0.00% 0/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	6.9% 2/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Skin and subcutaneous tissue disorders Rash maculo-papular	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Abdominal pain	7.1% 2/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Colitis	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Constipation	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Diarrhea	7.1% 2/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Dysphagia	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Nausea	7.1% 2/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Vomiting	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Immune system disorders Allergic reaction	0.00% 0/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	3.4% 1/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Infections and infestations Sepsis	7.1% 2/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	3.4% 1/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Infections and infestations Infections and infestations - Other	0.00% 0/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	3.4% 1/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Aspartate aminotransferase increased	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Lipase increased	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Lymphocyte count decreased	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	6.9% 2/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Neutrophil count decreased	7.1% 2/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	44.8% 13/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Platelet count decreased	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	17.2% 5/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations White blood cell decreased	7.1% 2/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	20.7% 6/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Metabolism and nutrition disorders Dehydration	7.1% 2/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	3.4% 1/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	3.4% 1/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	0.00% 0/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	3.4% 1/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Reproductive system and breast disorders Pelvic pain	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Blood and lymphatic system disorders Anemia	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	27.6% 8/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Blood and lymphatic system disorders Febrile neutropenia	7.1% 2/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	10.3% 3/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years

Measure	Arm A (Capecitabine, Temozolomide) n=28 participants at risk Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Cisplatin, Carboplatin, Etoposide) n=29 participants at risk Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	35.7% 10/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	79.3% 23/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
General disorders and administration site conditions Fatigue	64.3% 18/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	62.1% 18/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
General disorders and administration site conditions Fever	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	10.3% 3/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Skin and subcutaneous tissue disorders Alopecia	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	62.1% 18/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	14.3% 4/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	3.4% 1/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Skin and subcutaneous tissue disorders Rash maculo-papular	7.1% 2/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	3.4% 1/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Abdominal pain	10.7% 3/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	3.4% 1/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Constipation	14.3% 4/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	20.7% 6/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Diarrhea	25.0% 7/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	17.2% 5/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Dyspepsia	0.00% 0/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	10.3% 3/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Gastroesophageal reflux disease	7.1% 2/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Mucositis oral	10.7% 3/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	10.3% 3/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Nausea	53.6% 15/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	48.3% 14/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Gastrointestinal disorders Vomiting	28.6% 8/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	27.6% 8/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Alanine aminotransferase increased	7.1% 2/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	3.4% 1/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Alkaline phosphatase increased	17.9% 5/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	10.3% 3/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Aspartate aminotransferase increased	14.3% 4/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	13.8% 4/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Blood bilirubin increased	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	10.3% 3/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Creatinine increased	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	20.7% 6/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Lymphocyte count decreased	10.7% 3/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	17.2% 5/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Neutrophil count decreased	14.3% 4/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	37.9% 11/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Platelet count decreased	28.6% 8/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	48.3% 14/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations Weight loss	14.3% 4/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	13.8% 4/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Investigations White blood cell decreased	25.0% 7/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	41.4% 12/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Metabolism and nutrition disorders Anorexia	21.4% 6/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	13.8% 4/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Metabolism and nutrition disorders Hypoalbuminemia	10.7% 3/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	17.2% 5/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Metabolism and nutrition disorders Hypokalemia	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	24.1% 7/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	24.1% 7/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Musculoskeletal and connective tissue disorders Generalized muscle weakness	10.7% 3/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	6.9% 2/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Musculoskeletal and connective tissue disorders Pain in extremity	7.1% 2/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	0.00% 0/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Nervous system disorders Dysgeusia	3.6% 1/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	17.2% 5/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Nervous system disorders Headache	10.7% 3/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	6.9% 2/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Nervous system disorders Peripheral sensory neuropathy	14.3% 4/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	20.7% 6/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/28 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years	6.9% 2/29 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, up to 5 years