Clinical-benefit response in advanced non-small-cell lung cancer: A multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine

Background: The modest improvement in median survival of advanced non-small -cell lung cancer (NSCLC) by cisplatin-based chemotherapy has led to the cu rrent opinion that clinical benefit for the patient is at least as importan t an end-point as objective response rate (ORR) or survival. Clinical benef it response was the primary end-point of this prospective randomised trial in symptomatic, advanced stage IIIB/IV NSCLC, comparing single agent gemcit abine (GEM) to cisplatin-based chemotherapy. Patients and methods: Patients received either GEM (1000 mg/m(2), days 1, 8 and 15) or cisplatin (100 mg/m(2), day 1) plus Vindesine (3 mg/m(2), days 1 and 15) (PV), both every four weeks. Clinical benefit was measured by a s imple metric based on changes in a visual analogue symptom score list, the Karnofsky performance status and the weight. Results: One hundred sixty-nine patients were randomised (84 GEM, 85 PV). P rognostic factors and baseline symptoms were well balanced between the two arms. Most of the the objective responders and about half of the patients w ith disease stabilisation experienced clinical benefit. Compared to PV, a s ignificantly larger number of GEM-treated patients experienced a clinical b enefit (48.1 vs. 28.9%, P = 0.03) that lasted significantly longer (median duration 16 vs. 10 weeks, P = 0.01). No important differences in ORR, time- to-progression or median survival were observed. Grade 3 + 4 toxicity was s ignificantly higher in the PV-group for leukopenia (P = 0.0003), neutropeni a (P < 0.0001), nausea/vomiting (P = 0.0006), alopecia (P < 0.0001), and ne urotoxicity (P = 0.04). Some severe pulmonary toxicity to GEM was noted. Conclusion: Comparison of GEM with cisplatin-based therapy in symptomatic, advanced NSCLC demonstrates that GEM produces significantly a stronger and longer-lasting clinical benefit, probably due to its equal effectiveness in terms of ORR, time-to-progression or survival, combined with significantly less severe therapy-related toxicity.