Phase II trial of oral uracil/tegafur plus leucovorin in patients with hormone-refractory prostate carcinoma.
BACKGROUND
The current study evaluated the efficacy of oral uracil/tegafur (UFT) and leucovorin (LV) in patients with hormone-refractory metastatic prostate carcinoma.


METHODS
Twenty-eight patients with hormone-refractory metastatic carcinoma of the prostate who had undergone antiandrogen withdrawal and no more than 1 prior chemotherapy treatment were enrolled on a single-institution Phase II trial. Patients were treated with oral UFT at a dose of 300 mg/m2/d and oral LV at a dose of 90 mg/day for 28 days followed by 7 days off therapy on a 35-day cycle regimen.


RESULTS
Twenty-six patients were evaluable for response and toxicity. There was no response by objective criteria in 9 patients with measurable disease. Four responses by prostate-specific antigen (PSA) criteria (i.e., PSA decrease by > 50%) were noted (15%) lasting a mean of 20.5 weeks. Therapy was generally well tolerated, with 2 patients developing Grade 4 toxicity (1 patient each with diarrhea and hand-foot syndrome) and 4 patients having significant Grade 3 toxicity (anemia, hyperbilirubinemia, and vomiting) (Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria). Six patients had stable disease by clinical, laboratory, and radiologic criteria for an average of 5 cycles of treatment (25 wks).


CONCLUSIONS
Although UFT and LV are generally well tolerated in the setting of hormone-refractory metastatic prostate carcinoma, the combination has a low level of activity. Its toxicity and activity is similar to that observed when intravenous 5-fluorouracil or capecitabine are given alone. It may be an option for further investigations in combination regimens.
Bhandari
Manish S
MS
Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
Pienta
Kenneth J
KJ
Fardig
Judith
J
Olson
Karin
K
Smith
David C
DC
D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects
D005641:Tegafur; D014498:Uracil; D017430:Prostate-Specific Antigen; D002955:Leucovorin