Salvage therapy with oral metronomic cyclophosphamide and methotrexate for castration-refractory metastatic adenocarcinoma of the prostate resistant to docetaxel - Abstract

Medical Oncology Unit, La Maddalena Clinic for Cancer, University of Palermo, Italy.


To investigate the activity and toxicity of metronomic chemotherapy with low-dose oral cyclophosphamide (CTX) and methotrexate (MTX) in patients with metastatic CRPC that progresses after docetaxel. Patients with castration-resistant prostate cancer (CRPC) that progresses after docetaxel may benefit from receiving further chemotherapy.

Patients were treated with CTX 50 mg/d p.o. plus MTX 2.4 mg p.o. twice per week without rest periods. All patients received simultaneous luteinizing hormone-releasing hormone analogue. Prostate-specific antigen (PSA) response was defined as a 50% reduction on 2 evaluations at least 4 weeks apart. Objective response was measured according to the RECIST criteria. Pain relief was analyzed with the McGill-Melzack Pain Questionnaire. Simon's 2-stage design for phase II study was used. Time to progression and progression-free and overall survival were computed. Toxicity was recorded according to the CTC-NCCN criteria.

A PSA decrease ≥50% was recorded in 15 of 58 evaluable patients (25%), and objective partial response in 3 (18%) and stable disease in 4 (24%) of 17 patients with measurable disease. Disease in 10 patients (59%) progressed. Pain intensity decreased in 16 (30%), increased in 18 (33%), and remained stable in 18 (33%) patients. Five patients discontinued narcotic analgesics for a mean duration of 12 weeks. Transitory grade 3 leukopenia was observed in 4 cases (7%), grade 3 thrombocytopenia in 2 (3%), and grade 2 anemia in 4 (7%).

This study demonstrates the feasibility, activity, and tolerability of oral low-dose CTX and MTX given on a metronomic schedule in patients with CRPC progressing after docetaxel-based chemotherapy.

Written by:
Gebbia V, Serretta V, Borsellino N, Valerio MR.   Are you the author?

Reference: Urology. 2011 Nov;78(5):1125-30.
doi: 10.1016/j.urology.2011.08.010

PubMed Abstract
PMID: 22054386 Prostate Cancer Section


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