TY - JOUR
T1 - 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
AU - Vergote, I.
AU - Finkler, N.
AU - del Campo, J.
AU - Lohr, A.
AU - Hunter, J.
AU - Matei, D.
AU - Kavanagh, J.
AU - Vermorken, J. B.
AU - Meng, L.
AU - Jones, M.
AU - Brown, G.
AU - Kaye, S.
N1 - Funding Information:
This work was supported by Telik, Inc., Palo Alto, CA, USA.
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/9
Y1 - 2009/9
N2 - 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.
AB - 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.
KW - Canfosfamide
KW - Epithelial ovarian cancer
KW - Glutathione S-transferase
KW - Platinum refractory or resistant
KW - Prodrug
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U2 - 10.1016/j.ejca.2009.05.016
DO - 10.1016/j.ejca.2009.05.016
M3 - Article
C2 - 19515553
AN - SCOPUS:68749089764
SN - 0959-8049
VL - 45
SP - 2324
EP - 2332
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 13
ER -
