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

Abstract

Results: Metronomic CY was safe and well tolerated, and although lymphopaenia (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 PSA (absolute reduction and reduction in PSA velocity). The median duration of response was 7.5 months (range 3-18 months). Conclusions:Oral CY can be used on a metronomic basis safely in men with HRPC.The efficacy, low toxicity, low cost and ease of administration of CY justifies further studies in prostate cancer in combination with other agents.3

Continuous Docetaxel Chemotherapy Improves Therapeutic Efficacy in Murine Models of Ovarian Cancer

“…Studies have shown the benefits of shortening treatment-free periods in between cycles of chemotherapy by administering lower doses more frequently in a regimen termed metronomic therapy. Preclinical models and clinical trials have shown that metronomic administration of cytotoxic agents inhibits tumor growth to a greater extent than intermittent regimens administered at the MTD followed by long treatment-free periods (23,(28)(29)(30)(31). For the first time, we have completely eliminated treatment-free periods by administering DTX continuously through an injectable polymer-lipid implant formulation.…”

T-regulatory cell modulation: the future of cancer immunotherapy?

“…Low-dose cyclophosphamide has been used in a metronomic regimen in patients with end-stage cancer (Ghiringhelli et al, 2007) and conventional hormone-resistant prostate cancer (Lord et al, 2007), potentiating its anti-angiogenic and immunostimulatory properties and avoiding its high-dose toxic effects. Though the phase II prostate cancer study showed no relationship between clinical response and circulating Treg numbers, there was a reduction in TGF-b expression, which is crucial for nTregmediated suppression.…”

Effective oral combination metronomic chemotherapy with low toxicity for the management of castration-resistant prostate cancer

“…It was modified and converted to a fully peroral regimen. Therefore, doxorubicin and vinblastine were replaced with cyclophosphamide and etoposide both of which are also active in PC (3,16,(20)(21)(22)(23)(24). By combining secondary hormonal manipulation (ketoconazol, estramustine) with chemotherapy (etoposide, Sendoxan and estramustin) administered in a metronomic manner we sought to achieve a synergistic antitumor effect as previously described in experimental studies (23).…”

“…Several phase II trials with combination chemotherapy administered in a metronomic way in patients with CRPC have shown beneficial therapeutic effects (15)(16)(17)(18). One of the most promising regimens consists of ketoconazole in combination with doxorubicin alternating with vinblastine in combination with estramustine (KA/VE) (15,17).…”