Initial results of a phase II trial of high dose radiation therapy, 5-fluorouracil, and cisplatin for patients with anal cancer (E4292): an Eastern Cooperative Oncology Group study.
OBJECTIVE
A prospective clinical trial was performed to assess the response and toxicity associated with the use of high dose radiation therapy, 5-fluorouracil, and cisplatin in patients with anal cancer.


METHODS
Patients with anal cancer without distant metastasis were eligible for this study. Radiation therapy consisted of 59.4 Gy in 33 fractions; a 2 week break in treatment was taken after 36 Gy had been given. A treatment of 5-fluorouracil, 1,000 mg/m2 per day intravenously, was given for the first 4 days of radiation therapy, and cisplatin, 75 mg/m2 intravenously, was given on day 1 of radiation therapy. A second course of 5-fluorouracil and cisplatin was given after 36 Gy of radiation, when the radiation therapy was resumed.


RESULTS
Nineteen patients entered this study and received treatment. Thirteen (68%) had a complete response, 5 (26%) had a partial response, and 1 (5%) had stable disease. The patient with stable disease and one of the patients with a partial response had complete disappearance of tumor more than 8 weeks after completion of radiation therapy. Fifteen patients had toxicity of Grade 3 or higher: the worst toxicity was Grade 3 in eight patients, Grade 4 in six patients, and Grade 5 in one patient. The most common form of toxicity of Grade 3 or higher was hematologic. The one lethal toxicity was due to pseudomembranous colitis, which was a complication of antibiotic therapy for a urinary tract infection.


CONCLUSIONS
Radiation therapy, cisplatin, and 5-fluorouracil resulted in an overall response rate of 95%. Significant toxicity occurred, an indication that this regimen is near the maximal tolerated dose. A Phase III clinical trial is planned in which radiation therapy, cisplatin, and 5-fluorouracil will be used as an experimental arm.
Martenson
J A
JA
Mayo Clinic, Rochester, MN 55905, USA.
Lipsitz
S R
SR
Wagner
H
H
Kaplan
E H
EH
Otteman
L A
LA
Schuchter
L M
LM
Mansour
E G
EG
Talamonti
M S
MS
Benson
A B
AB
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects
D002945:Cisplatin; D005472:Fluorouracil