title: Phase 2 study of canfosfamide in combination with pegylated liposomal doxorubicin in platinum and paclitaxel refractory or resistant epithelial ovarian cancer.
abstract: BACKGROUND
  Canfosfamide is a novel glutathione analog activated by glutathione S-transferase P1-1. This study evaluated the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum resistant ovarian cancer. Patients with platinum resistant ovarian carcinoma and measurable disease received canfosfamide at 960 mg/m2 in combination with PLD at 50 mg/m2, intravenously day 1 in every 28 day cycles until tumor progression or unacceptable toxicities. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS).
  
  
  RESULTS
  Canfosfamide plus PLD combination therapy was administered at 960/50 mg/m2, respectively. Thirty-nine patients received a median number of 4 cycles (range 1.0-18.0). The ORR was 27.8% (95% CI, 14.2-45.2) with a disease stabilization rate of 80.6% (95% CI, 64.0-91.8) in the evaluable population. The CA-125 marker responses correlated with the radiological findings of complete response or partial response. The median PFS was 6.0 months (95% CI, 4.2-7.9) and median survival was 17.8 months. The combination was well tolerated. Myelosuppression was managed with dose reductions and growth factor support. Grade 3 febrile neutropenia was observed in 2 patients (5.1%). Non-hematologic adverse events occurred at the expected frequency and grade for each drug alone, with no unexpected or cumulative toxicities.
  
  
  CONCLUSIONS
  Canfosfamide in combination with PLD is well tolerated and active in platinum and paclitaxel refractory or resistant ovarian cancer. A randomized phase 3 study was conducted based on this supportive phase 2 study.
authors.affiliation: Telik, Inc, Palo Alto, CA, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Kavanagh
authors.forename: Charles F
authors.initials: CF
authors.lastname: Levenback
authors.forename: Pedro T
authors.initials: PT
authors.lastname: Ramirez
authors.forename: Judith L
authors.initials: JL
authors.lastname: Wolf
authors.forename: Carla L
authors.initials: CL
authors.lastname: Moore
authors.forename: Marsha R
authors.initials: MR
authors.lastname: Jones
authors.forename: Lisa
authors.initials: L
authors.lastname: Meng
authors.forename: Gail L
authors.initials: GL
authors.lastname: Brown
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bast
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005978:Glutathione / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017239:Paclitaxel / Q000627:therapeutic use; D017671:Platinum Compounds / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D017671:Platinum Compounds; C506643:liposomal doxorubicin; C107479:TER 286; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005978:Glutathione; D017239:Paclitaxel