Weekly paclitaxel/5-fluorouracil for recurrent ovarian cancer-A pilot study-

Abstract

5160 Background: Standard chemotherapy regimen for recurrent ovarian cancer has not been established. Weekly paclitaxel (PTX) has been reported to be effective for recurrent ovarian cancer. In breast and gastric cancer, PTX combined with 5-fluorouracil (5-FU) has been reported to be highly effective. We, therefore, performed basic and clinical study on this combination therapy to evaluate its efficacy for recurrent ovarian cancer in a preliminary manner. Methods: Ovarian cancer cell lines (OVCAR-3, PA-1) were exposed to PTX for 24 h followed by 5-FU for 1 h with higher dose or 24 h with lower dose and then incubated in drug-free medium for 95 h or 72 h, respectively. Cell growth inhibition was determined by MTT assay. The effects of drug combinations were analyzed by combination index (CI) based on median effect principle. Ten patients with recurrent ovarian cancer, who were pretreated with taxane and carboplatin and gave their informed consent to receive this combination therapy, were eligible. A fixed dose of PTX (80 mg/m2) on day 1, 8, and 15 was combined with bolus injection of 5-FU, at a starting dose of 250 mg/m2 per week on day 2, 9, and 16. The maximum dose of 5-FU was set at 500 mg/m2 in this preliminary study. Chemotherapy was given every four week. Response and toxicity was evaluated by RECIST and CA-125 criteria described by Rustin et al., NCI-CTC, respectively. Results: Combination treatment with PTX and 5-FU revealed synergistic cytotoxic effect against two ovarian cancer cell lines in vitro irrespective of administration schedule of 5-FU. A pilot study for patients with recurrent ovarian cancer revealed that one of five patients (20%) with measurable disease showed complete response with eight months of duration of response and four patients revealed stable disease. Two of five patients (40%) without measurable disease showed 75% response evaluated by CA-125 criteria. Major side effects were hematologic toxicity (grade 3–4 leukopenia: 7 cases), which was, however, easily manageable by G-CSF. Conclusions: Weekly PTX/5-FU could be safely administered for patients with recurrent ovarian cancer and can be involved in sequential chemotherapy followed by platinum-containing regimen for prolongation of platinum-free interval. No significant financial relationships to disclose.