Phase 3 randomised study of canfosfamide (Telcyta®, TLK286) versus pegylated liposomal doxorubicin or topotecan as third-line therapy in patients with platinum-refractory or -resistant ovarian cancer

I. Vergote*, N. Finkler, J. del Campo, A. Lohr, J. Hunter, D. Matei, J. Kavanagh, J. B. Vermorken, L. Meng, M. Jones, G. Brown, S. Kaye

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

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 with pegylated liposomal doxorubicin (PLD) or topotecan (TOPO), were randomised between CAN 1000 mg/m2 IV q 3 weeks or to either PLD 50 mg/m2 IV q 4 weeks or TOPO 1.5 mg/m2 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.

Original languageEnglish (US)
Pages (from-to)2324-2332
Number of pages9
JournalEuropean Journal of Cancer
Volume45
Issue number13
DOIs
StatePublished - Sep 2009

Keywords

  • Canfosfamide
  • Epithelial ovarian cancer
  • Glutathione S-transferase
  • Platinum refractory or resistant
  • Prodrug

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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