Phase II Randomized Study of Dose-Dense Docetaxel and Cisplatin Every 2 Weeks With Pegfilgrastim and Darbepoetin Alfa With and Without the Chemoprotector BNP7787 in Patients With Advanced Non-small Cell Lung Cancer (CALGB 30303)

IntroductionWe investigated dose-dense docetaxel and cisplatin in patients with measurable non-small cell lung cancer in a randomized phase II study without [A] or with [B] a putative chemoprotective agent, BNP7787.Patients and MethodsChemotherapy-naive patients with stage IIIB (effusion) or IV, performance status 0 to 1, and adequate organ function were eligible. Treatment with docetaxel 75 mg/m2 followed by cisplatin 75 mg/m2 over 1 hour day 1 with darbepoetin 200 μg day 1 and pegfilgrastim 6 mg day 2 without/with BNP7787 before cisplatin was repeated every other week for up to 6 cycles. The primary end point was to differentiate between grade ≥2 neurotoxicity rates of 30% on [A] and 10% on [B]. Feasibility was prospectively defined as febrile neutropenia in <10% of patients and ≤1 treatment delay per cycles 1 to 3 and 4 to 6 in <20% of patients.ResultsOf 160 patients enrolled, 5 never started therapy and 4 were ineligible. Neurotoxicity grade ≥2 occurred in 32% on [A] and 29% on [B]. The incidence of febrile neutropenia was 4% on [A] and 3% on [B]. Treatment delays occurred in 13% and 20% of patients on [A] and [B], respectively. Completion rates for 3/6 cycles were 84%/51% on [A] and 84%/53% on [B]. Objective response rates were 55% on [A] and 51% on [B]. Median progression-free/overall survival times were 5.5/10.7 on [A] and 6.5/14.1 month on [B].ConclusionsThis dose-dense treatment regimen is active, feasible, and tolerable. Its further investigation in the curative setting in non-small cell lung cancer should be considered. BNP7787 did not result in significant protection from neurotoxicity.