Phase II trial of metronomic chemotherapy as salvage therapy for patients with metastatic breast cancer.

To evaluate the efficacy and tolerability of metronomic chemotherapy (which is the continuous administration of chemotherapy at relatively low minimally toxic doses on a frequent schedule of administration at close regular intervals with no prolonged drug-free breaks) in metastatic breast cancer patients as salvage therapy.In this phase II study we evaluated the clinical efficacy and tolerability of low dose, oral Methotrexate (MTX) and Cyclophosphamide (CTX) in patients with metastatic breast cancer. Between January 2004 and December 2005, 42 patients received MTX 2.5mg bid on day 1 and 2 each week and CTX 50mg/day administered continuously.Forty two patients were evaluable. The overall clinical benefit was 31% complete response, partial response and stable disease (CR+PR+SD >or=24 weeks), while the overall response rate was 16.7% (none of the patients attained CR). Toxicity was generally mild. The most common non hematological toxicity was elevation in transaminases level, it was reported in 40.4% of patients and was reversible, while mild grade 1 or 2 neutropenia was the most common hematological toxicity, (28.5% of patients). Median time to response was 3+/-0.18 while progression free survival (PFS) among patients with clinical benefit was 10 months (95% CI 6.65-13.44).This phase II study shows that, the combination of continuously low dose MTX and CTX is an active minimally toxic and significantly cost effective regimen for the treatment of metastatic breast cancer patients.