Combination More Effective Than High-Dose Cisplatin in NSCLC

HAMBURG, Germany--Increasing cisplatin dose intensity was less effective than combining standard cisplatin (Platinol) with paclitaxel (Taxol) in a multicenter multinational study of advanced non-small cell lung cancer (NSCLC) reported at ASCO.

Ulrich Gatzemeier, MD, of Hamburg, said that patients treated with paclitaxel/cisplatin had higher response rates and longer time to disease progression than those on high-dose cisplatin.

The investigators studied 414 patients with advanced NSCLC who had not received previous chemotherapy.

Patients were randomized to single-agent high-dose cisplatin (100 mg/m²) or combination paclitaxel and standard-dose cisplatin (paclitaxel 175 mg/m² by 3-hr infusion, followed by cisplatin 80 mg/m²). Courses were repeated every 3 weeks. Median follow-up was approximately 20 months.

As might be expected, patients were significantly less able to tolerate the high-dose cisplatin regimen (median of 3 courses) than the standard-dose combination regimen (median of 5 courses).

"The major explanation for this difference might be that in the protocol we had stop rules for the high-dose cisplatin," Dr. Gatzemeier said. "In case of grade 1 renal toxicity and grade 2 neurotoxicity, the treatment had to be stopped."

Dr. Gatzemeier reported overall response rates in patients with measurable disease of 26% for cisplatin/paclitaxel vs 17% for high-dose cisplatin (P = .0001). The time to progression was also significantly longer for cisplatin/paclitaxel (median, 4.1 months vs 2.7 months, P = .026). Median survival and 1-year survival were not significantly different between the two arms (8.1 vs 8.6 months, and 30% vs 36%, respectively).

Dr. Gatzemeier said that there was crossover to second-line therapy when disease progressed, and that some patients on single-agent cisplatin did receive a taxane. "This could have contributed to the similar survival rates between the two arms, despite the higher response rate with the combination."

Dr. Gatzemeier reported that there were no significant differ-ences in nonhematologic toxicities between the two arms. "The paclitaxel/cisplatin arm resulted in quality of life improvements in certain symptom scales and physical functioning," he said.