Two schedules of chemotherapy for patients with non-small cell lung cancer in poor performance status: a phase II randomized trial.

We present experience from a phase II randomized clinical trial, comparing standard gemcitabine as monotherapy with low-dose gemcitabine in long infusion in a doublet with cisplatin at reduced dose for patients with non-small cell lung cancer (NSCLC) and who are unfit for standard platin-based chemotherapy. Eligible patients had microscopically confirmed NSCLC in stage IIIB (wet) or IV, were chemo-naive, and were in poor performance status or presented with significant comorbidity. Standard treatment with gemcitabine, 1250 mg/m in 20-30 min on days 1 and 8 as monotherapy (arm A) was compared with low-dose gemcitabine in long infusion (200 mg/m in 6 h on day 1) and cisplatin at 60 mg/m on day 2 (arm B). Both treatment schedules were repeated every 3 weeks until disease progression, unacceptable toxicity, or to a maximum of six cycles. A total of 112 patients (83 male, 29 female, median age 66 years) were randomized between arm A (57 patients) and B (55 patients). The two groups were balanced for prognostic factors. Fifty-three patients in arm A and 52 in arm B received at least one application of chemotherapy and were evaluable for toxicity and response. The median number of cycles was four and five for arms A and B, respectively. Except for grade 3 anemia (one patient in arm A and two in arm B), no other major toxicity was seen. Regarding response to treatment, arm B was superior: 1 complete response and 13 partial remissions (response rate 26.9%) as compared with five partial remissions (response rate 9.4%) in arm A (P<0.01). The median time to progression was 3.8 and 5.6 months, and the median survival was 4.3 and 6.8 months for arms A and B, respectively (P<0.05). Treatment with low-dose gemcitabine in long infusion and cisplatin at reduced dose has very low toxicity, is effective, was found to be superior to monotherapy with gemcitabine in standard doses, and is suitable for patients with NSCLC who cannot tolerate a standard platin-based doublet.