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)

J Thorac Oncol. 2008 Oct;3(10):1159-65. doi: 10.1097/JTO.0b013e318186fb0d.

Abstract

Introduction: We 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 methods: Chemotherapy-naive patients with stage IIIB (effusion) or IV, performance status 0 to 1, and adequate organ function were eligible. Treatment with docetaxel 75 mg/m followed by cisplatin 75 mg/m over 1 hour day 1 with darbepoetin 200 mug 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.

Results: Of 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].

Conclusions: This 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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / secondary
  • Adenocarcinoma, Bronchiolo-Alveolar / drug therapy
  • Adenocarcinoma, Bronchiolo-Alveolar / secondary
  • Adult
  • Aged
  • Anemia / drug therapy
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / secondary
  • Cisplatin / administration & dosage
  • Darbepoetin alfa
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Erythropoietin / analogs & derivatives*
  • Erythropoietin / therapeutic use
  • Feasibility Studies
  • Female
  • Filgrastim
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Hematinics / therapeutic use
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Maximum Tolerated Dose
  • Mesna / analogs & derivatives*
  • Mesna / therapeutic use
  • Middle Aged
  • Neoplasm Staging
  • Neutropenia / drug therapy
  • Polyethylene Glycols
  • Prognosis
  • Recombinant Proteins
  • Survival Rate
  • Taxoids / administration & dosage

Substances

  • Hematinics
  • Recombinant Proteins
  • Taxoids
  • Erythropoietin
  • Granulocyte Colony-Stimulating Factor
  • Docetaxel
  • Darbepoetin alfa
  • pegfilgrastim
  • Polyethylene Glycols
  • 2,2'-dithiodiethanesulfonic acid
  • Mesna
  • Filgrastim
  • Cisplatin