Alimta® Versus Its Combination With Carboplatin in Advanced Non-small-cell Lung Cancer in Patients Performance Status 2

Summary

Optimal management of patients with advanced NSCLC and with PS 2 remains controversial and underrepresented in clinical trials, typically accounting for 5 to 10% of enrolled patients. Patient PS 2 proportion in population-based studies is considerably higher than that included in clinical trials. Management of patients with PS of 2 in clinical practice is empirical and inconsistent. Patients have median overall survival of 3 to 5 months in randomized trials, and treatment options include best supportive care, single-agent and combination chemotherapy. Retrospective studies have suggested that patients PS 2 may benefit from first-line chemotherapy in terms of symptom improvement and overall survival. In many of these studies, single-agent chemotherapy was compared with best supportive care alone. Data on the role of cisplatin-based combinations for patients with PS 2 is more scant, with one study questioning its benefit, and another interrupting accrual because of undue toxicity. With regards to carboplatin, the Cancer and Leukemia Group B (CALGB) study 9730 compared paclitaxel plus carboplatin versus paclitaxel alone in a subgroup of 107 patients with PS 2; the median overall survival was significantly longer in group treated with combination chemotherapy (4.7 versus 2.4 months). Combination chemotherapy with carboplatin and paclitaxel also produced a statistically significantly higher incidence of severe hematological and non-hematological toxicities. On the basis of aforementioned results, a recent European panel stated that carboplatin-based or low-dose cisplatin-based doublets might represent alternative options to single-agent chemoterapy in patients PS 2. Outside clinical trials, single-agent chemotherapy with a 3rd generation agent remains valid option for patients PS2. Results demonstrate that pemetrexed is an agent with established single-agent activity in NSCLC, and suggest it is a potential candidate for combinations with platinum and other agents currently utilized for patients with advanced NSCLC. Favorable toxicity profile of pemetrexed suggests that this agent is an ideal candidate for single agent testing and in combination among patients with PS 2. Substantial doubt remains in the comparative benefit from monotherapy versus combination. Starting dose and schedule of pemetrexed were set for this study based on its current labeling in the 2nd line treatment of metastatic NSCLC and 1st line treatment of malignant pleural mesothelioma.

Conditions

• Non Small Cell Lung Carcinoma

Interventions

DRUG

Pemetrexed

Pemetrexed, 500 mg/m2 + Pretreatment \[dexamethasone + vitamin B12 + folic acid, as per pemetrexed label\] + Antiemetic therapy at investigator's discretion.

DRUG

Carboplatin

Carboplatin \[Target AUC 5 IV infusion,based on Calvert formula,GFR estimated using estimated creatinine clearance per Cockcroft and Gault formula, obtained prior to each cycle\].

Sponsors & Collaborators

• Eli Lilly and Company

  collaborator INDUSTRY

• Instituto Nacional de Cancer, Brazil

  lead OTHER_GOV

Principal Investigators

• Carlos G Ferreira, PhD · National Cancer Institute, France

• Rogerio Lilenbaum, MD · The Mount Sinai Comprehensive Cancer Center

• Carlos Henrique E Barrios, MD · Pontifícia Universidade Católica do RS

• Carlos Augusto M. Beato, MD · Hospital Amaral Carvalho

• José Rodrigues, MD · Instituto do Câncer Arnaldo Vieira Carvalho - ICAVC

• Yeni Neron, MD · Centro de Pesquisas Oncológicas - CEPON

• André Murad, PhD · Lifecenter Hospital

• Ronaldo A Ribeiro, PhD · Instituto do Câncer do Ceará - ICC

• Fábio Franke, MD · Hospital de Caridade de Ijuí - CACON

• Mauro Zukin, MD · National Cancer Institute, France

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-04-30

Primary Completion

2012-01-31

Completion

2012-12-31

Countries

• United States
• Brazil

Study Locations