title: Salvage therapy with oral metronomic cyclophosphamide and methotrexate for castration-refractory metastatic adenocarcinoma of the prostate resistant to docetaxel.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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%).
  
  
  CONCLUSIONS
  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.
authors: Medical Oncology Unit, La Maddalena Clinic for Cancer, University of Palermo, Italy.
authors: Vittorio
authors: V
authors: Gebbia
authors: Vincenzo
authors: V
authors: Serretta
authors: Nicolò
authors: N
authors: Borsellino
authors: Maria Rosaria
authors: MR
authors: Valerio
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary*; D059250:Administration, Metronomic; D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016879:Salvage Therapy; D043823:Taxoids / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D003520:Cyclophosphamide; D008727:Methotrexate