Randomized phase III trial of gemcitabine and cisplatin vs. gemcitabine alone in patients with advanced non-small cell lung cancer and a performance status of 2: the CAPPA-2 study.

Platinum-based chemotherapy is the standard treatment for patients with advanced non-small cell lung cancer (NSCLC), but the evidence of its efficacy among ECOG performance status (PS)2 patients is weak because these patients are usually excluded from clinical trials; concern exists about tolerability and feasibility of standard chemotherapy in these patients. No prospective randomized trial has tested the addition of cisplatin to single-agent chemotherapy in patients with advanced NSCLC and PS2. CAPPA-2 was a multicenter, randomized phase 3 study for first-line treatment of PS2 patients with advanced NSCLC. Patients, aged 18-70, were eligible if they had stage IV or IIIB with malignant pleural effusion or metastatic supraclavicular nodes (TNM VI edition) and adequate organ function. Patients in standard arm received gemcitabine 1200 mg/m(2) days 1 and 8. Patients in experimental arm received cisplatin 60 mg/m(2) day 1 plus gemcitabine 1000 mg/m(2) days 1 and 8. All treatments were repeated every 3 weeks, up to 4 cycles, unless disease progression or unacceptable toxicity. Primary endpoint was overall survival (OS). To have 80% power of detecting hazard ratio (HR) 0.71, corresponding to an increase in median OS from 4.8 to 6.8 months, 285 deaths were required. The study was stopped in June 2012 after the enrolment of 57 patients, due to the slow accrual and the report of positive results from a similar study. Median OS was 3.0 months with single-agent gemcitabine and 5.9 months with cisplatin plus gemcitabine (HR 0.52, 95% CI 0.28-0.98, p = 0.039). Combination chemotherapy produced longer PFS (median 1.7 vs. 3.3 months, HR 0.49, 95% CI 0.27-0.89, p = 0.017) and higher response rate (4% vs. 18%, p = 0.19), without substantial increase in toxicity. The addition of cisplatin to single-agent gemcitabine improves survival as first-line treatment of PS2 patients with advanced NSCLC.