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.