Low-dose methotrexate and cyclophosphamide in recurrent ovarian cancer

Abstract

e16574 Background: Ovarian cancer continues to be the leading cause of death secondary to gynecologic cancers among women. Despite the fact that new chemotherapeutic drugs have been found effective, the prognosis of these women continues to be poor. Metronomic chemotherapy, chronic administration of chemotherapy at relatively low, minimally toxic doses on a frequent schedule with no prolonged drug-free breaks, is a potentially novel approach to the control of advanced cancer disease. It is thought to work primarily through antiangiogenic mechanisms and has, as an advantage, the property of significantly reducing toxic side-effects. Purpose: to evaluate the efficacy and toxicity of metronomic chemotherapy using low dose methotrexate and cyclophosphamide in patients with refractory pretreated ovarian cancer. Methods: From May 2007 to July 2008, 11 patients with refractory pretreated ovarian adenocarcinoma were included. Patient's characteristics: median age 51 years (range 41–64), ECOG 0–2, progression after more than two lines of chemotherapy for recurrent disease. Treatment: low-dose oral methotrexate 2.5 mg bd on days 1 and 2 each week and cyclophosphamide 50 mg/day administered continuously until disease progression. Follow-up: every month clinical examination, ECOG, blood test; every two months CA-125; every four months CT-scan. Results: All patients were evaluable for response and toxicity. There was no complete response; 2 pts (18.18%) - partial response and the overall clinical benefit rate was 54.54%. The median time to progression was 4.4 month. Main toxicities according to WHO criteria were: grade 1–2 gastrointestinal toxicities (nausea, vomiting) 4 pts (36.36%), grade 1–2 anemia 4 pts (36.36%), grade 1–2 neutropenia 2 pts (18.18%). No grade 3–4 toxicities was observed. Conclusions: Metronomic metotrexate-cyclophosphamide is minimally toxic and effective in heavily pretreated recurrent ovarian cancer. In conclusion, metronomic regimen could represent a potentially significant palliative treatment for these patients. A better understanding of mechanism of actions would help determine the optimal dose and schedule for metronomic chemotherapy regimens as antiangiogenic therapy. No significant financial relationships to disclose.