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

International Collaboration

cited authors

  • 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

funding text

  • 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.

Publication Date

  • September 1, 2009

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start page

  • 2324

end page

  • 2332

volume

  • 45

issue

  • 13

WoS Citations

  • 74

WoS References

  • 32