Phase II randomized study of dose-dense docetaxel (Doc) and cisplatin (Cis) every two weeks with pegfilgrastim (Pfil) and darbepoetin alfa (Darb) with and without the chemoprotector BNP7787 in patients with advanced non-small cell lung cancer (NSCLC): CAL

Abstract

7617 Background: We sought to explore the toxicity, feasibility, and response rate of dose-dense Doc and Cis with growth factor support without [A] and with [B] a novel chemoprotector in patients with NSCLC. Methods: Patients with measurable disease, stage IIIB (effusion) or IV, performance status (PS) 0–1, no prior chemotherapy, and adequate organ function were eligible. Treatment with Doc 75 mg/m2 ? Cis 75 mg/m2 both IV over 1 hr day 1 with Darb 200 mcg SC day 1 and Pfil 6 mg SC day 2 randomized to without/with BNP before Cis was repeated every other week (1 cycle = 2 weeks) for up to 6 cycles. Response was determined after 3 and 6 cycles. Because of anticipated neurotoxicity (NT), the primary statistical endpoint was to differentiate between grade =2 NT rates of 30% in [A] and 10% in [B]: 90% power, two-tailed p<0.10, 76 patients per arm. Feasibility was prospectively defined as febrile neutropenia in <10% of patients and =1 treatment delay per cycles 1–3 and 4–6 in <20% of patients. Objective response rates of >35% were required to merit further investigation. Results: Between 8/04 and 3/06, 160 patients were enrolled but 5 never started therapy and 4 were ineligible: male/female, 99/52; white/black/other, 126/23/2; median age 62 (range, 30–88); PS 0/1, 69/82; stage IIIB/IV 14/137; [A]/[B], 76/75 well balanced. Sensory/motor/either NT grade =2 occurred in 28/14/32% on [A] and 19/19/29% on [B]. The incidence of febrile neutropenia was 1%. Treatment was delayed in cycles 1–3/cycles 4–6 in 3/3 patients in [A] and 1/5 patients in [B]. Completion rates for 3/6 cycles were 87/51% in [A] and 84/52% in [B]. By intent to treat, complete/partial response rates were 4/46% in [A] and 3/47% in [B]. Median estimated overall/progression-free survival times are10/6 months in [A] and 11/6 months in [B]. Overall, grade 3+4 neutropenia and thrombocytopenia occurred in =10% and anemia in 12% of patients. Non-hematologic toxicity was mild. Six deaths were thought to be treatment related. Conclusions: This dose-dense treatment regimen is feasible, tolerable, and worthy of further investigation in NSCLC. BNP did not result in significant protection from NT. No significant financial relationships to disclose.