A phase I study of oral UFT given concomitantly with standard preoperative radiotherapy for rectal cancer.
BACKGROUND
Preoperative radiotherapy is standard treatment for rectal cancer and is often combined with 5-fluorouracil-based chemotherapy. UFT, a new oral 5FU derivative, given daily during a course of radiotherapy mimics the effect of continuous-infusion 5FU.


OBJECTIVE
To determine the maximum tolerated dose of oral UFT and leucovorin with preoperative pelvic irradiation for rectal cancer, and assess tumor response.


METHODS
In this phase 1 trial, 16 patients aged 42-79 years with tumors within 12 cm of the anal verge received radiotherapy, 45 Gy over 5 weeks, an escalating dose of oral UFT, and a fixed dose of 30 mg/day leucovorin. UFT and leucovorin were given for 28 consecutive days concomitant with the first 4 weeks of radiotherapy. Surgery was scheduled for 4-6 weeks after completion of radiotherapy. The surgical procedure was determined by the surgeon at the time of surgery.


RESULTS
No grade III toxicity was seen at 200 mg/m2/day UFT. Of eight patients who received 240 mg/m2/day UFT, one developed grade IV diarrhea; of four patients who received 270 mg/m2/day UFT, one was hospitalized with grade IV diarrhea and leukopenic fever and died during hospitalization. Of the 15 evaluable patients, 9 had pathologic tumor downstaging including 4 patients with complete response. Only one patient required a colostomy.


CONCLUSIONS
The MTD of UFT together with leucovorin and preoperative radiotherapy for rectal cancer is 240 mg/m2. The major toxicity was diarrhea. Downstaging was noted in 60% of patients, allowing sphincter-preserving surgery even in patients with low tumors.
Oncology Institute, Sheba Medical Center, Tel Hashomer, Israel. raphipf@sheba.health.gov.il
M Raphael
MR
Pfeffer
Yulia
Y
Kundel
Meir
M
Zehavi
Raphael
R
Catane
Moshe
M
Koller
Oded
O
Zmora
Ruth
R
Elkayam
Zvi
Z
Symon
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003082:Colectomy; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009367:Neoplasm Staging; D011878:Radiotherapy / Q000379:methods; D012004:Rectal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D005641:Tegafur / Q000008:administration & dosage*; D016896:Treatment Outcome; D014463:Ultrasonography; D014498:Uracil / Q000008:administration & dosage*
D005641:Tegafur; D014498:Uracil; D005492:Folic Acid; D002955:Leucovorin