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.

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 1000mg/m² IV q 3weeks or to either PLD 50mg/m² IV q 4weeks or TOPO 1.5mg/m² IV d1-5 q 3weeks.

About 461 patients were randomised after stratification for ECOG performance status, prior therapy, and bulky (>5cm) 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.

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.