Phase II study of repeated single 24-hour infusion of low-dose 5-fluorouracil for palliation in symptomatic hormone-refractory prostate cancer.
BACKGROUND
To assess the efficacy and toxicity of repeated single 24-hour infusion of low-dose 5-fluorouracil for symptomatic hormone-refractory prostate cancer using relevant endpoints of palliation and biological response.


METHODS
25 patients with histologically confirmed prostatic adenocarcinoma and symptomatic progressive disease despite one or several hormonal treatments and chemotherapy were included in the study. Treatment consisted of a single 24-hour infusion of 500 mg/m(2) 5-fluorouracil (5-FU) to be repeated on day 21. This regimen was continued until either progression or serious toxicity occurred. Response was assessed by serial measurements of serum prostate-specific antigen (PSA) as well as by health-related quality-of-life instruments (EORTC QLQ-C30 and McGill-Melzack Present Pain Intensity Scale) every 3 weeks. In 10 patients with bidimensionally measurable metastases, objective responses were assessed every 3 months.


RESULTS
A mean number of four courses of repeated single 24-hour infusion of 5-FU was administered (range 2-6). Toxicity was absent or mild, and no patient had to be withdrawn from therapy. All patients required analgesics prior to treatment and only 3 patients experienced a significant reduction in pain for 9 weeks, the remaining patients experienced no deterioration for a mean duration of 12 weeks (6-18 weeks). Five patients (20%) demonstrated a biological response of a 50% or greater decrease in PSA from baseline, including 2 (12%) with a 75% or greater decline for 10 weeks (range 6-16 weeks). One partial remission was observed among 10 patients with measurable lesions lasting 12 weeks; 4 patients had stable disease with a mean duration of 12 weeks. Mean survival time from the onset of treatment with 5-FU was 7 months (2-12 months).


CONCLUSIONS
Though less toxic than other 5-FU regimens, repeated single low-dose 24-hour infusion is of no significant benefit in patients with symptomatic hormone-refractory prostate cancer.
Bex
A
A
Urologische Klinik und Poliklinik, Medizinische Einrichtungen der Universität-Gesamthochschule Essen, Germany. a.bex@nki.nl
Otto
T
T
Lümmen
G
G
Rübben
H
H
D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D011471:Prostatic Neoplasms / Q000188:drug therapy*
D000726:Androgen Antagonists; D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil