title: A pilot study of AFL-T (doxorubicin, 5-fluorouracil, leucovorin, and tamoxifen) combination chemotherapy for hormone-refractory prostate cancer.
abstract: BACKGROUND
  Tamoxifen had been used to treat advanced prostate cancer with limited success. In vitro data suggested that tamoxifen could enhance the cytotoxic effect of chemotherapeutic agents, including doxorubicin, on prostate cancer cell lines. We applied this observation into a phase II trial for patients with hormone refractory prostate cancer (HRPC).
  
  
  METHODS
  The AFL-T regimen consisted of doxorubicin 30 mg/m2/day on day 1; 5-FU 2,000 mg/m2/day 24-hour infusion and leucovorin 200 mg/m2/day 24-hour infusion on days 15 and 29; tamoxifen 50 mg/m2 four times daily on days 1, 2, 16, 17, 30, and 31. The protocol was designed to be of low dose-intensity and tolerable to most HRPC patients who may have reduced bone marrow reserve and poor renal function. Between Feb. 1994 and April 1999, 17 patients (median age 67, range 60-81) with HRPC were enrolled. Extensive hormonal manipulations had been done prior to the chemotherapy. Three patients had measurable diseases, 14 had only bone metastases, and all had elevated PSA levels (median 498 ng/ml, range 7.4-3,970 ng/ml).
  
  
  RESULTS
  All 17 patients were eligible for analysis of toxicity. ECOG Grade III/IV leukopenia and thrombocytopenia occurred in 1 and 3 patients, respectively. There was no febrile neutropenia; there was no treatment-related mortality. Grade III/IV nausea, vomiting, mucositis, and diarrhea were noted in 0, 0, 1 and 0 patient, respectively. There was no venous thrombosis. One partial response, 1 stable disease, and 1 progressive disease were found in the three patients with measurable lesions. Eleven of the 17 patients (64.7%, 95% confidence interval: 41-88%) who were eligible for the evaluation of PSA response (PSA decrease > 50% for at least 6 weeks) were responders. The median overall and progression-free survivals were 13 and 7 months, respectively. Seventy-six percent of patients showed decreased analgesic usage or enhanced performance status.
  
  
  CONCLUSIONS
  AFL-T, that has a low toxicity profile, is comparable to most other active regimens in terms of the PSA response rate. Randomized trials are needed to determine if there exists a survival benefit for patients with HRPC.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: C C
authors.initials: CC
authors.lastname: Lin
authors.forename: C H
authors.initials: CH
authors.lastname: Hsu
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: T C
authors.initials: TC
authors.lastname: Tsai
authors.forename: A L
authors.initials: AL
authors.lastname: Cheng
authors.forename: Y S
authors.initials: YS
authors.lastname: Pu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D004317:Doxorubicin; D017430:Prostate-Specific Antigen; D002955:Leucovorin; D005472:Fluorouracil