Dose escalation in chemoradiation for anal cancer: preliminary results of RTOG 92-08.
OBJECTIVE
Radiation Therapy Oncology Group experience with chemoradiation for anal cancer has shown a local failure rate of 20% to 30% with radiotherapy doses of 45 to 50 cGy. This study was undertaken to assess the effect of higher radiotherapy doses on toxicity, local control, and survival in this disease.


METHODS
Forty-seven patients with anal cancers measuring > or = 2 cm were treated with a concurrent combination of two cycles of 5-fluorouracil infusion (1000 mg/m2 over 24 hrs for 4 days) and mitomycin C (10 mg/m2 bolus) plus 59.6 Gy of pelvic and perineal radiotherapy administered over 8.5 weeks, including a 2-week rest period. Patients were followed for toxicity, disease status, and colostomy-free survival. Twenty-three (49%) patients had advanced (T3-4) primary tumors; 42 (92%) patients had NO disease, and 36 (77%) patients had squamous histology. For perspective, a comparative analysis was made with 147 patients treated on the previous RTOG protocol for anal cancers (RTOG 87-04) with identical chemotherapy but radiotherapy doses of 40 to 50.4 Gy.


RESULTS
Transient hematologic and skin toxicity predominated during treatment or in early follow-up. One patient developed septicemia and died of multiple gastrointestinal toxicities. Twelve (26%) patients had greater than grade 3 complications and, of these, 9 (20%) had hematologic side effects alone. A comparative analysis with 147 patients treated on RTOG protocol 87-04 showed no significant differences in pretreatment characteristics of disease extent, performance status, or histology. A mandatory 2-week split in the current chemoradiation protocol contrasted with 12% of patients having a 2-week or greater treatment break in RTOG 87-04. Patients treated on the current protocol (RTOG 92-08) had a markedly lower incidence of > or = grade 3 dermal toxicity (34% vs. 55%) but a higher colostomy rate at 1 year (23% vs. 6%) and at 2 years (30% vs. 7%) compared with RTOG 87-04.


CONCLUSIONS
Numerical increases in radiotherapy dose over those used in conventional chemotherapy regimens for anal cancers do not appear to increase local control when given in split-course fashion. For higher radiotherapy doses (> 50 Gy) to increase local control, radiation may have to be given in continuous fashion, which almost certainly means that our threshold of acceptable acute toxicity, particularly dermal toxicity, may have to be raised.
John
M
M
Central California Cancer Research Group, University of California, San Francisco, and St. Agnes Hospital, Fresno, California, USA.
Pajak
T
T
Flam
M
M
Hoffman
J
J
Markoe
A
A
Wolkov
H
H
Paris
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D019583:Dose Fractionation, Radiation; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D010865:Pilot Projects; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome
D016685:Mitomycin; D005472:Fluorouracil