Combination carboplatin and pemetrexed for the treatment of platinum-sensitive recurrent ovarian cancer.

5523 Background: More efficacious, less toxic combinations are needed to treat platinum-sensitive recurrent ovarian cancer. Pemetrexed (Pem) is a multitargeted antifolate that has a manageable toxicity profile and has been combined with carboplatin in other cancers.,Phase II study of carboplatin AUC 5 with Pem 500 mg/m both administered IV on day 1, with Decadron, B12, and folate premedication, and given every 21 d for six cycles with the possibility of receiving 8 if benefit derived. Eligibility included platinum sensitive (>6 mos without progression after last platinum regimen), measurable (by RECIST) recurrent ovarian, peritoneal, or fallopian tube cancer, PS ≤ 2, ≤ 2 prior regimens for recurrence, and normal bone marrow, liver/renal function. Primary objective was response rate. Other endpoints included toxicities, time to progression (TTP), and survival. A RR of ≥ 31% was considered worthy of further phase III testing.,45 patients have been enrolled, and accrual is complete. 1 pt was ineligible. 3 pts withdrew before 2 cycles were completed because of grade 3 fatigue/weakness, grade 3 diarrhea and a carboplatin reaction, respectively and were not evaluated for response. 27 pts completed at least 6 cycles. No dose reductions (DR's) were required because of toxicities in 28 of 41 pts who received at least 2 cycles. 13 pts had DR's as a result of myelosuppression or GI toxicity; 11 had one DR and 2 had two DR's. 44 pts are evaluable for toxicities. Grade 3 and 4 toxicities are as follows: neutropenia (19 pts), platelets (11 pts), leukopenia (7 pts), anemia (4 pts), fatigue (4 pts), nausea (2 pts), diarrhea (2 pts), dizziness (2 pts), and 1 pt each experienced hypokalemia, vomiting, constipation, anorexia, memory impairment, pulmonary embolism. 14 pts had a carboplatin allergy. No significant rashes nor mucositis occurred. 41 pts were evaluable for RR, TTP, and survival. Overall RR was 61%; 1CR (2%), 24 PR's (59%), 14 SD (34%), and 2 PD (5%). Median TTP was 4.6 months (95% CI 3.2 -5.9) while median PFS was 7.7 months (95% CI 6.7 - 10.1).,Carboplatin/Pem is a well-tolerated regimen with significant activity in platinum-sensitive recurrent ovarian cancer. Further testing of this regimen in this population is warranted. [Table: see text].