title: Metronomic oral cyclophosphamide plus prednisone in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer.
abstract: We evaluated the efficacy and safety of metronomic oral cyclophosphamide (CTX) and prednisone in metastatic castration-resistant prostate cancer (mCRPC) patients. We analyzed retrospectively patients with mCRPC previously treated with docetaxel, and who received metronomic CTX (from 50 mg PO daily to 150 mg PO, 14 days/7 days off) and prednisone 10 mg PO daily between September 2009 and April 2014 were analyzed. The primary endpoint was prostate-specific antigen (PSA) decrease ≥50 %. Secondary analysis included PSA decrease ≥30 %, time-to-treatment failure (TTF) and toxicity. Demographics and baseline characteristics were summarized using descriptive statistics. PSA response and adverse events were reported as relative rates. Kaplan-Meier estimates were calculated and plotted for time-to-event endpoints. Forty patients were evaluated. The median age was 69 years old (52-86), 12 (30.0 %) patients presented a Karnofsky performance status (KPS) of <80 %, and 34 (85 %) presented with bone with or without nodal metastases. Median pre-treatment PSA was 192 ng/dL (7-2696 ng/dL). All patients were previously exposed to docetaxel, including 33 (82.5 %) with docetaxel-refractory disease. PSA response rate was achieved in eight (20.0 %) out of 40 patients. Additionally, PSA declines of ≥30 % occurred in 14 (35.0 %) patients. The median TTF was 3 months (95 % confidence interval 2.5-3.5). The treatment was well tolerated. Grade 3/4 lymphopenia was reported in 11 (27.5 %) patients and was the only grade 3-4 toxicity reported. Metronomic oral CTX showed activity and safety in docetaxel-pretreated mCRPC patients. This regimen deserves further investigation in this setting.
authors.affiliation: Division of Medical Oncology, Instituto do Câncer do Estado de São Paulo (ICESP), Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Arnaldo 251, 5o andar, São Paulo, 01246-000, São Paulo, Brazil, romualdo.sousa@icesp.org.br.
authors.forename: Romualdo
authors.initials: R
authors.lastname: Barroso-Sousa
authors.forename: Leonardo Gomes
authors.initials: LG
authors.lastname: da Fonseca
authors.forename: Karla Teixeira
authors.initials: KT
authors.lastname: Souza
authors.forename: Ana Carolina Ribeiro
authors.initials: AC
authors.lastname: Chaves
authors.forename: Ariel Galapo
authors.initials: AG
authors.lastname: Kann
authors.forename: Gilberto
authors.initials: G
authors.lastname: de Castro
authors.forename: Carlos
authors.initials: C
authors.lastname: Dzik
mesh_terms: D059250:Administration, Metronomic; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D003520:Cyclophosphamide; D017430:Prostate-Specific Antigen; D011241:Prednisone