Short schedule of cisplatin and vinorelbine: A dose-finding study in non-small-cell lung cancer

Objectives: A dose- finding study of a new cisplatin/ vinorelbine schedule was done to increase activity of the combination, and improve compliance of non- small- cell lung cancer patients. Methods: Beginning with cisplatin 40 mg/ m(2) on days 1, 2 and vinorelbine 20 mg/ m(2) on days 1, 3, increasing dose levels up to the maximum tolerated dose ( MTD) were tested in a series of 6- patient cohorts. If 3 of 6 patients experienced dose- limiting toxicity in the first 3 cycles, the previous dose was considered the recommended dose ( RD). Once the MTD was reached, granulocyte- colony- stimulating factor was prophylactically added to the treatment of a new patient cohort to improve the therapeutic ratio. Results: We enrolled 35 stage IIIA/ B or IV patients between August 2001 and February 2002. The RD was cisplatin 45 mg/ m 2 and vinorelbine 25 mg/ m(2), with relative dose intensities ( RDIs) of 95 and 97%, respectively, and an actual received dose intensity ( ARDI) of 28.62 and 16.07 mg/ m(2) / week, respectively. Overall grade 3 - 4 toxicities were: neutropenia ( 71%), febrile neutropenia ( 25%), anemia ( 8%), and constipation ( 17%). The overall response rate was 64.3% ( CI: 44.1 - 81.4%). Conclusions: ARDI and RDI of our modified cisplatin/ vinorelbine regimen were not inferior to those of conventional weekly schedules; its acceptable toxicity profile and manageability may justify its use in clinical practice.