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/m(2) 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.
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/m(2) 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.
Authors: Leandro E Mainetti; Viviana R Rozados; Ana Rossa; R Daniel Bonfil; O Graciela Scharovsky Journal: J Cancer Res Clin Oncol Date: 2010-03-27 Impact factor: 4.553
Authors: Romualdo Barroso-Sousa; Leonardo Gomes da Fonseca; Karla Teixeira Souza; Ana Carolina Ribeiro Chaves; Ariel Galapo Kann; Gilberto de Castro; Carlos Dzik Journal: Med Oncol Date: 2014-12-18 Impact factor: 3.064
Authors: Vincenzo Cerullo; Iulia Diaconu; Lotta Kangasniemi; Maria Rajecki; Sophie Escutenaire; Anniina Koski; Valentina Romano; Noora Rouvinen; Tamara Tuuminen; Leena Laasonen; Kaarina Partanen; Satu Kauppinen; Timo Joensuu; Minna Oksanen; Sirkka-Liisa Holm; Elina Haavisto; Aila Karioja-Kallio; Anna Kanerva; Sari Pesonen; Petteri T Arstila; Akseli Hemminki Journal: Mol Ther Date: 2011-06-14 Impact factor: 11.454
Authors: N Penel; S Clisant; E Dansin; C Desauw; M Dégardin; L Mortier; M Vanhuyse; F Bonodeau; C Fournier; J-L Cazin; A Adenis Journal: Br J Cancer Date: 2010-03-30 Impact factor: 7.640
Authors: K K Y Cham; J H E Baker; K S Takhar; J A Flexman; M Q Wong; D A Owen; A Yung; P Kozlowski; S A Reinsberg; E M Chu; C-W A Chang; A K Buczkowski; S W Chung; C H Scudamore; A I Minchinton; D T T Yapp; S S W Ng Journal: Br J Cancer Date: 2010-06-08 Impact factor: 7.640
Authors: Christina A To; Robert W Hsieh; James Scott McClellan; Walter Howard; Nancy J Fischbein; Janice M Y Brown; Dean W Felsher; Alice C Fan Journal: BMJ Case Rep Date: 2012-09-07