The non hematologic AEs occurred at the expected frequency and grade for each drug selleck compound alone, with no unexpected or cumulative toxicities. Efficacy Thirty nine patients were in the ITT population. Thirty six patients received at least 2 cycles of canfosfamide with PLD combination therapy, had an adequate base line tumor assessment, and at least 1 follow up scan, defining the EE population. An ORR by RECIST of 25. Inhibitors,Modulators,Libraries 6% in the ITT population and 27. 8% in the EE population was reported. One CR and 9 partial responses were reported. Patients with Inhibitors,Modulators,Libraries platinum refractory and primary resistant disease had comparable ORR to patients with secondary platinum resistant disease. Patients who were assessed as CR or PR had decrements in CA 125 tumor markers commensurate with their tumor responses.

The median Inhibitors,Modulators,Libraries time to objective response was 2. 9 months and the med ian duration of response was 9. 7 months. Twenty patients had SD resulting in a disease stabilization rate of 76. 9% in the ITT population and 80. 6% in the EE population. The median Inhibitors,Modulators,Libraries duration of SD was 6. 4 months. The med ian PFS was 6. 0 months and the med ian survival was 17. 8 months. comparable for patients who had platinum refractory or primary platinum resistant disease of the poorest prog nosis and for patients who had secondary platinum resistant disease. This phase 2 trial is the first to characterize the safety and efficacy of canfosfamide in combination with PLD. The toxicity of PLD is distinct with the most common The percentage of patients alive at 12, 18 and 24 months was 64. 1%, 48. 6% and 35. 5%, respectively.

Inhibitors,Modulators,Libraries Discussion Patients diagnosed with metastatic ovarian cancer even tually become refractory or resistant to platinum and paclitaxel regimens and are subsequently treated with non platinum monotherapy. Two approved drugs for the treatment of platinum resistant patients include topotecan and PLD. Combination therapy in plati num refractory or resistant recurrent disease has not been proven to be more effective than single agents and is associated with increased toxicity. In single agent studies, both canfosfamide and PLD have been shown to be active in patients with platinum and paclitaxel refractory or resistant ovarian cancer. Canfosfamide has shown a response rate of 15. 6% in the 3 weekly dose schedule and 19% in the weekly dosing, and a DSR of 50% in phase 2 studies.

Pegylated liposomal doxorubicin has been shown to have a response rate of 12. 3% and a DSR of 40% in the pla tinum resistant population in a phase 3 randomized selleck chemicals Ganetespib study. In our phase 2 study, the response rate of 25. 6% and DSR of 76. 9% supports that the combination regimen is more active in the treatment of platinum resistant ovar ian cancer than expected from either agent alone. These results are likely due to the distinct mechanisms of action for each drug, as well as non overlapping toxici ties with prior carboplatin paclitaxel therapy and canfos famides non cross resistance with platinum and taxanes.