Phase 2 study of canfosfamide in combination with pegylated liposomal doxorubicin in platinum and paclitaxel refractory or resistant epithelial ovarian cancer.
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.
Kavanagh
John J
JJ
Telik, Inc, Palo Alto, CA, USA.
Levenback
Charles F
CF
Ramirez
Pedro T
PT
Wolf
Judith L
JL
Moore
Carla L
CL
Jones
Marsha R
MR
Meng
Lisa
L
Brown
Gail L
GL
Bast
Robert C
RC
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
D017671:Platinum Compounds; C506643:liposomal doxorubicin; C107479:TER 286; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005978:Glutathione; D017239:Paclitaxel