title: Phase 1-2a multicenter dose-ranging study of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy for patients with advanced non-small cell lung cancer.
abstract: BACKGROUND
  We aimed to evaluate the safety and efficacy of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy in patients with locally advanced or metastatic non-small cell lung cancer.
  
  
  METHODS
  This was a phase 1-2a, multicenter, dose-ranging trial that enrolled patients with stage IIIB or IV non-small cell lung cancer with measurable disease. Patients received canfosfamide in doses ranging from 400 to 1000 mg/m2 intravenously (IV) with carboplatin at area under the curve 6 IV and paclitaxel at 200 mg/m2 IV day 1 every 3 weeks. The primary end point was objective response rate, and the secondary endpoints were safety and progression-free survival.
  
  
  RESULTS
  One hundred twenty-nine patients were treated with canfosfamide at dose levels of 400 (n = 3), 500 (n = 51), 750 (n = 54), and 1000 mg/m2 (n = 21). Objective tumor responses by RECIST were observed in 40 patients [34% (95% confidence interval [CI], 26-44)], the median progression-free survival was 4.3 months (95% CI, 3.7-5.2) and the median survival 9.9 months (95% CI, 7.7-11.9). The percent of patients alive at 1 year was 43.1%. The overall safety profile of the combination was acceptable and consistent with the profiles of the individual agents. In an exploratory analysis, patients receiving the optional maintenance canfosfamide therapy had a prolonged median survival of 16.8 months compared with those eligible for but not receiving maintenance therapy at 8.8 months (hazard ratio = 0.38, p < 0.001).
  
  
  CONCLUSIONS
  The combination of canfosfamide with carboplatin and paclitaxel chemotherapy is well tolerated and active. Maintenance canfosfamide may further improve outcomes. This regimen is worthy of additional study.
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA. lvsequist@partners.org
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
authors.forename: Panos M
authors.initials: PM
authors.lastname: Fidias
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Temel
authors.forename: Tatjana
authors.initials: T
authors.lastname: Kolevska
authors.forename: Michael S
authors.initials: MS
authors.lastname: Rabin
authors.forename: Ralph V
authors.initials: RV
authors.lastname: Boccia
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Belt
authors.forename: Mark S
authors.initials: MS
authors.lastname: Huberman
authors.forename: Ostap
authors.initials: O
authors.lastname: Melnyk
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Mills
authors.forename: Craig W
authors.initials: CW
authors.lastname: Englund
authors.forename: David C
authors.initials: DC
authors.lastname: Caldwell
authors.forename: James G
authors.initials: JG
authors.lastname: Keck
authors.forename: Lisa
authors.initials: L
authors.lastname: Meng
authors.forename: Marsha
authors.initials: M
authors.lastname: Jones
authors.forename: Gail L
authors.initials: GL
authors.lastname: Brown
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lynch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003603:Cytotoxins; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005978:Glutathione / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; C107479:TER 286; D016190:Carboplatin; D005978:Glutathione; D017239:Paclitaxel