Original article Oral low-dose cyclophosphamide in metastatic hormone refractory prostate cancer (MHRPC) A Nicolini a, *, PA Mancini b , P Ferrari a , L Anselmi a , G Tartarelli a , V Bonazzi c , A Carpi d , R Giardino e a Department of Internal Medicine, University of Pisa, Via Roma 67, Pisa 56126, Italy b Unit of Urology, ASL 6, Livorno, Italy c ANT, Bologna, Italy d Department of Reproduction and Aging, University of Pisa, Pisa, Italy e Department of Experimental Surgery, Research Institute Codivilla Putti Rizzoli Orthopaedic Institute, Bologna, Italy Received 22 July 2004 Available online 25 August 2004 Abstract The chemotherapeutic approach to hormone-refractory metastatic prostate cancer (MHRPC) for a long time included only estramustine. Then, attempts have been made with other various agents as cyclophosphamide, vinblastine, etoposide, taxanes and carboplatinum. Although the new drugs and combinations have increased the response rate of MHRPC, they have had no impact on the natural history of MHRPC, which is about 1 year as median time of survival. After an occasional observation of prolonged response in a patient with MHRPC treated with a very well tolerated oral low-dose of cyclophosphamide, from February 1996 to October 2002, seven more patients with MHRPC and progressive disease were consecutively recruited. Response to treatment was evaluated by conventional radiological procedures and/or serial serum PSA measurements. The decline of PSA value was considered to assess the response consistent with the response guidelines from the prostate specific antigen-working group. All eight studied patients continuously received oral low dose cyclophosphamide until progression or the occurrence of significant toxicity. So far three patients (37.5%) progressed (PD), two (25%) showed PR and the three remaining SD. Response rate was 25%, and clinical benefit occurred in 62.5% of the studied patients. In the five patients with clinical benefit on cyclophosphamide median duration of clinical benefit, PR and SD were 9, 24 + and 8 months, respectively. In these five patients median overall survival times from cyclophosphamide and from the first regimen of chemotherapy were 17 and 32 + months respectively, while in the three patients with PD they were 4 and 13 months. The same interval times in patients with ≥50% decline of serum PSA were 29 and 50.5 months, while in those with <50% decline of the same marker, they were 13 and 32 months, respectively. Grade 2 or 3 neutropenia were observed in all the studied patients. In four (50%) of them pulmonary and urinary infections that were easily cured by the common antibiotics occurred. These data suggest that the metronomic use of cyclophosphamide, given alone, has similar or higher activity with lower toxicity than when administered with other active drugs. So it can be an useful option before or after the use of other single or combined potentially active chemotherapeutic agents. © 2004 Elsevier SAS. All rights reserved. Keywords: Prostate cancer; Cyclophosphamide 1. Introduction In the last decades PSA screening is becoming a common procedure and most prostate cancers are detected while local- ized with an early stage. However some prostate cancers with early stage and most of those that at the presentation are locally advanced will eventually progress to metastatic dis- ease. As yet hormone ablation therapy is the cornerstone of treatment for patients with advanced prostate carcinoma. Androgen deprivation achieves stabilization or regression of disease in more than 80% of patients but the median duration of response after hormonal therapy in metastatic disease is less than two years [1–3]. After progression to an androgen independent stage median survival is approximately one year [3–5]. At this point treatment with chemotherapy is indi- * Corresponding author. E-mail address: a.nicolini@int.med.unipi.it (A. Nicolini). Biomedicine & Pharmacotherapy 58 (2004) 447–450 www.elsevier.com/locate/biopha 0753-3322/$ - see front matter © 2004 Elsevier SAS. All rights reserved. doi:10.1016/j.biopha.2004.08.006