Phase 3 randomised study of canfosfamide (Telcyta (R), TLK286) versus pegylated liposomal doxorubicin or topotecan as third-line therapy in patients with platinum-refractory or -resistant ovarian cancer
Article
Vergote, I., Finkler, N., del Campo, J., Lohr, A., Hunter, J., Matei, D., Kavanagh, J., Vermorken, J. B., Meng, L., Jones, M., Brown, G., Kaye, S., ASSIST-1 Study Grp
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This work was supported by Telik, Inc., Palo Alto, CA, USA.
abstract
Rationale: Canfosfamide HC1 (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 50 mg/m(2) IV q 4 weeks or TOPO 1.5 mg/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 CS with third-line therapy. This might have important consequences for other recurrent OC trials. (C) 2009 Elsevier Ltd. All rights reserved.