title: 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).
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Wake Forest University, Winston-Salem, North Carolina, USA. aamiller@wfubmc.edu
authors.forename: Antonius A
authors.initials: AA
authors.lastname: Miller
authors.forename: Xiaofei F
authors.initials: XF
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Gu
authors.forename: Philip
authors.initials: P
authors.lastname: Hoffman
authors.forename: Jamil
authors.initials: J
authors.lastname: Khatri
authors.forename: Frank
authors.initials: F
authors.lastname: Dunphy
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.forename: Michael
authors.initials: M
authors.lastname: Bolger
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Mark R
authors.initials: MR
authors.lastname: Green
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000740:Anemia / Q000188:drug therapy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D000068256:Darbepoetin alfa; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005240:Feasibility Studies; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006397:Hematinics / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D015080:Mesna / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000188:drug therapy; D011092:Polyethylene Glycols; D011379:Prognosis; D011994:Recombinant Proteins; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D006397:Hematinics; D011994:Recombinant Proteins; D043823:Taxoids; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D000068256:Darbepoetin alfa; C455861:pegfilgrastim; D011092:Polyethylene Glycols; C027032:2,2'-dithiodiethanesulfonic acid; D015080:Mesna; D000069585:Filgrastim; D002945:Cisplatin