Maintenance metronomic chemotherapy combined with conventional treatment for metastatic breast cancer patients

Abstract

Background: The treatment duration for metastatic breast cancer patients remains a controversial issue, with no overall survival benefit for continuous chemotherapy with increased toxicity. This study was carried out to evaluate the benefit of adding metronomic chemotherapy to conventional treatment regarding progression free survival, response rate and toxicity. Methods: Patients received first line treatment for their metastatic disease either chemotherapy followed by maintenance metronomic chemotherapy with or without hormonal therapy or primarily treated with hormonal therapy concomitant with metronomic chemotherapy. Metronomic chemotherapy consists of cyclophosphamide 50 mg tablet daily and methotrexate 2.5mg twice daily on days 2 and 5 weekly, continued until disease progression or development of unacceptable toxicity. Her2 +ve patients didn't receive trastuzumab. Results: After median follow up of 24 months (range: 9 months - 30 months), 40 patients were assessed, the progression free survival was 42.5 % and the median time to disease progression was 10.6 months. The overall clinical benefit (CR + PR + SD) was 42.5 % with no G3/4 toxicities encountered for metronomic therapy. Only G1/2 leucopenia (40%), G1/2 gasteritis (62.5%), one patient developed grade 3 increased transaminases and resume treatment with 50% dose reduction. The median time to disease progression was 13.5 months for ER +ve, Her2-ve compared to 8.5 months for ER + ve, Her2 + ve, 8 months for ER-ve, Her2 + ve and 8 months for triple negative. The difference was statistically significant (P value = .018). Univariate and multivariate analysis found that ER -ve, Her2 +ve and the presence of visceral metastasis are the most significant negative prognostic factors for time to disease progression whereas patients with bone only metastasis and ER + ve, HER2 neu -ve have the best outcome. Conclusions: Maintenance metronomic cyclophosphamide and methotrexate demonstrated efficacy and provided durable disease stabilization especially for ER positive patients. The low costs and minimal toxicity support its use as an additional therapeutic tool.