Salvage Therapy With Oral Metronomic Cyclophosphamide and Methotrexate for Castration refractory Metastatic Adenocarcinomaof the Prostate Resistant to Docetaxel

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Abstract

OBJECTIVE To investigate the activity and toxicity of metronomic chemotherapy with low-dose oralcyclophosphamide (CTX) and methotrexate (MTX) in patients with metastatic CRPC thatprogresses after docetaxel. Patients with castration-resistant prostate cancer (CRPC) that progressesafter docetaxel may benefit from receiving further chemotherapy.METHODS Patients were treated with CTX 50 mg/d p.o. plus MTX 2.4 mg p.o. twice per week without restperiods. All patients received simultaneous luteinizing hormone-releasing hormone analogue.Prostate-specific antigen (PSA) response was defined as a 50% reduction on 2 evaluations at least4 weeks apart. Objective response was measured according to the RECIST criteria. Pain reliefwas analyzed with the McGill-Melzack Pain Questionnaire. Simon’s 2-stage design for phase IIstudy was used. Time to progression and progression-free and overall survival were computed.Toxicity was recorded according to the CTC-NCCN criteria.RESULTS A PSA decrease 50% was recorded in 15 of 58 evaluable patients (25%), and objective partialresponse in 3 (18%) and stable disease in 4 (24%) of 17 patients with measurable disease. Diseasein 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 amean duration of 12 weeks. Transitory grade 3 leukopenia was observed in 4 cases (7%), grade3 thrombocytopenia in 2 (3%), and grade 2 anemia in 4 (7%).CONCLUSION This study demonstrates the feasibility, activity, and tolerability of oral low-dose CTX and MTXgiven on a metronomic schedule in patients with CRPC progressing after docetaxel-basedchemotherapy.
Lingua originaleEnglish
pagine (da-a)1125-1130
Numero di pagine6
RivistaUrology
Volume78
Stato di pubblicazionePublished - 2011

All Science Journal Classification (ASJC) codes

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