Brachytherapy and continuous infusion 5-fluorouracil for treatment of locally advanced, lymph node negative, prostate cancer: a phase I trial.
BACKGROUND
5-fluorouracil (5-FU) is a known radiosensitizer that enhances efficacy, in vivo and in vitro, when administered during radiotherapy. The following study was performed to evaluate the toxicity of continuous infusion 5-FU administered concomitant with brachytherapy in patients with locally advanced prostate cancer.


METHODS
Over a 26-month period, a total of 25 patients with newly diagnosed, locally advanced prostate cancer underwent radioactive gold (Au198) brachytherapy. Twenty-four of 25 patients were surgically staged and confirmed node negative. Au198 seed placement was performed transperineally under fluoroscopic and ultrasonographic guidance using an average of 195 mCi of Au198. Within 4 hours after seed placement, 25 patients received 5-FU administered as a continuous infusion over 4 days, at 1 of 8 dose levels ranging from 200-1100 mg/m2/day. Patients had clinical follow-up for a minimum of 1 year. Decreases in serum prostate specific antigen (PSA) and prostate volume (normalized to pretreatment values) were determined at 12 months.


RESULTS
5-FU associated toxicity was negligible, with Grade 1 nausea in four patients and no Grade 2 or higher toxicity. No unique locoregional toxicity was noted. At 12 months after treatment, PSA values decreased on average to 16.4% of pretreatment values. Twelve-month prostate volumes decreased to 55% of the pretreatment values.


CONCLUSIONS
These findings suggest that continuous infusion 5-FU can be administered safely concomitant with brachytherapy at doses up to 1100 mg/m2 per day for 4 days.
See
W A
WA
Department of Urology, The University of Iowa, Iowa City 52242-1089, USA.
Dreicer
R
R
Wheeler
J A
JA
Forest
P K
PK
Loening
S
S
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001918:Brachytherapy; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000627:therapeutic use*; D006050:Gold Radioisotopes / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011879:Radiotherapy Dosage
D000970:Antineoplastic Agents; D006050:Gold Radioisotopes; D011838:Radiation-Sensitizing Agents; D005472:Fluorouracil