Alternating Doublets: Establishing the Optimal Multifractionated Dosing Schedule to Administer Docetaxel, Cisplatin, Gemcitabine, and Vinorelbine in Combination

Abstract

The purpose was to determine the optimal multifractionated (MF) dosing schedule to permit the delivery of four active agents in nonsmall cell lung cancer simultaneously in alternating doublets (docetaxel-cisplatin alternating with gemcitabine-vinorelbine). Three MF schedules were used: schedule A weekly; schedule B twice weekly for 2 weeks repeated every 21 days; and schedule C twice weekly every other week. Dose fractions were fixed for each component drug: docetaxel 50 mg/m² plus cisplatin 20 mg/m² and gemcitabine 500 mg/m² plus vinorelbine 25 mg/m². GCSF 480 µg was administered as a single dose concomitant with chemotheray if the WBC was between 1500 and 3500 cells/mm³. Hematological toxicity, particularly leukopenia and anemia, was the predominant adverse effect observed and was demonstrated on all three schedules. Schedule B was not feasible in that none of the seven cycles were completed and six of seven required hospitalization for febrile neutropenia. The delivery of a four-drug combination chemotherapy regimen consisting of docetaxel, cisplatin, gemcitabine, and vinorelbine is feasible with an alternating doublet multifractionated dosing scheme with either a weekly or twice weekly every other week schedule.