The efficacy and toxicity of topotecan in second line chemotherapy in platinum resistant ovarian cancer

Ovarian cancer is the fifth leading cause of cancer death in women. In Poland it affects 3 000 women every year. Half of them die despite the treatment. The first-line therapy includes the cytoreduction surgery followed by chemotherapy. The administration of paltinum (carboplatin or cisplatin) has become a conventional first-line chemotherapeutic strategy for advanced epithelial ovarian carcinoma. Platinum is administrated either alone, or most often in combination with taxane. Approximately 10–15% of patients achieve and maintain complete response to therapy. Patients develop platinum resistant disease with requires second-line therapy. Topotecan, topoisomerase I inhibitor is currently irecommended for the treatment of recurrent and platinum-resistant ovarian cancer. The overall response rate to treatment with topotecan ranges from 19-33% in platinum-sensitive to 14–18% in platinum-resistant patients.
Objective: The objective of this study was to evaluate the efficacy and toxicity of topotecan in platinum-resistant epithelial ovarian cancer cases.
Material and methods: We administered topotecan as second-line chemotherapy to 28 women with platinum-resistant FIGO III and IV ovarian cancer. Inclusion criteria icluded the lack of response during platinum including chemotherapy courses (average after 4.1 courses). All patients had measurement changes in abdomen cavity confirmed by ultrasound or tomography and recieved topotecan intravenously 1.0–1.5 mg/m²/day as 30 min. infusion for 5 consecutive days per cycles. The dose of topotecan was cut from 1.5 mg/m2 to 1.0 mg/m² because of granulocytopenia (less than 1000/mm³) established one day before the start of a subsequent course. Cycles were repeated every 28 days. All patient were evaluated for toxicity and response. The chemotherapy was continued until disease progresion but no longer than 6 months. In the estimation of the results of treatment we applied the WHO criteria.
Results: A complete response was observed in 2 cases (7.14%), a partial response in 6 cases (21.4%). The median duration of the response was 29,5 weeks (range 6–53). The remission were achieved after an average of 8.1 weeks (range 4–12). Among 12 patients with ascites in 11 (91.7%) the abdomen puncture rate decreased. The main adverse effect was hematological toxicity. Fourteen (60.8%) patients developed Grade III/IV neutropenia, five (21.7%) developed Grade IV thrombocytopenia. In non-hematological toxicity only in the case of two patients mild nausea and vomitting were observed.
Conclusion: Topotecan is effective in ovarian cancer patient who have failed in the platinum based regiment.