Low Dose Metronomic Oral Cyclophosphamide for Hormone Resistant Prostate Cancer: A Phase II Study

Purpose

Cyclophosphamide is a bifunctional alkylating agent long associated with immune activation. Continuous, uninterrupted, low (so-called metronomic) doses of cyclophosphamide can lead to enhanced immunity against a variety of antigens possibly by targeting regulatory T cells and/or tumor angiogenesis. In this study we tested the observations from animal models and evaluated the safety and efficacy of continuous low dose oral cyclophosphamide in patients with hormone resistant prostate cancer.

Materials and Methods

A total of 80 patients were recruited during a 2-year period and 58 received at least 2 cycles (8 weeks) of 50 mg/m² oral cyclophosphamide to be included in the safety and intent to treat analysis.

Results

Metronomic cyclophosphamide was safe and well tolerated, and although lymphopenia (up to grade 3) was observed in a third of all patients, there were no clinical complications. The response rate was 34.5% inclusive of objective and prostate specific antigen (absolute reduction and reduction in prostate specific antigen velocity). The median duration of response was 7.5 months (range 3 to 18).

Conclusions

Oral cyclophosphamide can be used on a metronomic basis safely in men with hormone resistant prostate cancer. The efficacy, low toxicity, low cost and ease of administration of cyclophosphamide justifies further studies in prostate cancer in combination with other agents.

Key Words: cyclophosphamide, prostatic neoplasms

Abbreviations and Acronyms: CY, cyclophosphamide, HRPC, hormone resistant prostate cancer, LH-RH, luteinizing hormone releasing hormone, PC, prostate cancer, PSA, prostate specific antigen, PSAV, prostate specific antigen velocity, T reg, regulatory t cells