RATIONALE: Canfosfamide HCl (CAN) is a glutathione analogue prodrug that is activated by glutathione S-transferase P1-1 and induces apoptosis. CAN is synergistic in vitro with carboplatin, paclitaxel and anthracyclines. METHODS:Patients with platinum-refractory or -resistant ovarian cancer (OC) who had progressed on second-line therapy withpegylated liposomal doxorubicin (PLD) or topotecan (TOPO), were randomised between CAN 1000 mg/m(2) IV q 3 weeks or to either PLD 50mg/m(2) IV q 4 weeks or TOPO 1.5mg/m(2) IV d1-5 q 3 weeks. RESULTS: About 461 patients were randomised after stratification for ECOG performance status, prior therapy, and bulky (>5 cm) disease. Groups were well balanced. In the control arm 58% and 42% were treated with PLD and TOPO, respectively. CAN was well tolerated with the most common grade 3-4 toxicities of 5% anaemia, 4% neutropaenia (no febrile neutropaenia), 4% thrombocytopaenia, and 7% vomiting. Progression-free survival (PFS) and overall survival (OS) were significantly higher in the control arm (p<0.001 and p<0.01, respectively). In a subgroup analysis PFS and OS tended to be higher with PLD than with TOPO. CONCLUSION: CAN was well tolerated. This is the first randomised study showing an increased OS with third-line therapy. This might have important consequences for other recurrent OC trials.
RCT Entities:
RATIONALE: CanfosfamideHCl (CAN) is a glutathione analogue prodrug that is activated by glutathione S-transferase P1-1 and induces apoptosis. CAN is synergistic in vitro with carboplatin, paclitaxel and anthracyclines. METHODS:Patients with platinum-refractory or -resistant ovarian cancer (OC) who had progressed on second-line therapy with pegylated liposomal doxorubicin (PLD) or topotecan (TOPO), were randomised between CAN 1000 mg/m(2) IV q 3 weeks or to either PLD 50mg/m(2) IV q 4 weeks or TOPO 1.5mg/m(2) IV d1-5 q 3 weeks. RESULTS: About 461 patients were randomised after stratification for ECOG performance status, prior therapy, and bulky (>5 cm) disease. Groups were well balanced. In the control arm 58% and 42% were treated with PLD and TOPO, respectively. CAN was well tolerated with the most common grade 3-4 toxicities of 5% anaemia, 4% neutropaenia (no febrile neutropaenia), 4% thrombocytopaenia, and 7% vomiting. Progression-free survival (PFS) and overall survival (OS) were significantly higher in the control arm (p<0.001 and p<0.01, respectively). In a subgroup analysis PFS and OS tended to be higher with PLD than with TOPO. CONCLUSION:CAN was well tolerated. This is the first randomised study showing an increased OS with third-line therapy. This might have important consequences for other recurrent OC trials.
Authors: Evanthia Galanis; Pamela J Atherton; Matthew J Maurer; Keith L Knutson; Sean C Dowdy; William A Cliby; Paul Haluska; Harry J Long; Ann Oberg; Ileana Aderca; Matthew S Block; Jamie Bakkum-Gamez; Mark J Federspiel; Stephen J Russell; Kimberly R Kalli; Gary Keeney; Kah Whye Peng; Lynn C Hartmann Journal: Cancer Res Date: 2014-11-14 Impact factor: 12.701
Authors: Rachel N Grisham; Kathleen N Moore; Michael S Gordon; Wael Harb; Gwendolyn Cody; Darragh F Halpenny; Vicky Makker; Carol A Aghajanian Journal: Clin Cancer Res Date: 2018-05-29 Impact factor: 12.531
Authors: John J Kavanagh; Charles F Levenback; Pedro T Ramirez; Judith L Wolf; Carla L Moore; Marsha R Jones; Lisa Meng; Gail L Brown; Robert C Bast Journal: J Hematol Oncol Date: 2010-03-11 Impact factor: 17.388