Phase II study of alternating doses of vinorelbine in combination with cisplatin for non-small cell lung cancer (NSCLC): a disappointing experience.

Abstract:  In both Phase III trials of vinorelbine-cisplati n (VP) versus single-agent vinorelbine, the received vinorelbine dose intensities were 18.8 and 21.1 mg/m2 per week in the VP arms. Vinorelbine was administered at the weekly dose of 30 mg/m2. A new structure of the vinorelbine-cisplati n regimen delivering alternating doses of vinorelbine (35 mg/m2 on weeks 1, 3, 5 and 17.5 mg/m2 on weeks 2 and 4) was reported to increase the vinorelbine dose intensity in patients with non-small cell lung cancer (NSCLC). To further analyze the ability of such an alternating vinorelbine schedule to enhance vinorelbine delivery, a Phase II study of VP was conducted in NSCLC patients using the previously published alternating doses of vinorelbine for 6 cycles. Cisplatin was administered on weeks 1, 5 and every 6 weeks thereafter, at a dose of 75 mg/m2 in the first 14 patients and at a dose of 100 mg/m2 in the 18 remaining patients. The intended vinorelbine dose intensity was 26.25 mg/m2 per week. The median delivered dose intensities of vinorelbine calculated during the first 8-week period were: all patients, 17.9 mg/m2 per week; patients treated with cisplatin 75 mg/m2, 18.1 mg/m2 per week; patients receiving cisplatin 100 mg/m2, 17.9 mg/m2 per week; naive patients 18.2 mg/m2 per week and previously treated patients. 13.2 mg/m2 per week. Reductions and delays in the vinorelbine treatment mostly occurred on weeks 3 and 7, which are times of high-dose treatments (35 mg/m2) according to the protocol. The partial response rate was 34% (95% C.I. = 26-42%). Median survival was 21 weeks. The main toxicities were febrile neutropenia (nine patients, including two septic deaths) and constipation Grades 3 and 4 (five patients). CONCLUSION: The use of alternating doses of vinorelbine within the VP regimen did not lead to higher vinorelbine delivered dose intensities than those reported with a standard weekly 30 mg/m2 administration.