Adjuvant chemoradiotherapy of advanced resectable rectal cancer: results of a randomised trial comparing modulation of 5-fluorouracil with folinic acid or with interferon-α.
BACKGROUND
Standard adjuvant chemoradiotherapy of rectal cancer still consists of 5-fluorouracil (5-FU) only. Its cytotoxicity is enhanced by folinic acid (FA) and interferon-α (INFα). In this trial, the effects of FA and IFNα on adjuvant 5-FU chemoradiotherapy in locally advanced rectal cancer were investigated.


METHODS
Patients with R(0)-resected rectal cancer (UICC stage II and III) were stratified and randomised to a 12-month adjuvant chemoradiotherapy with 5-FU, 5-FU+FA, or 5-FU+IFNα. All patients received levamisol and local irradiation with 50.4 Gy.


RESULTS
Median follow-up was 4.9 years (n=796). Toxicities (WHO III+IV) were observed in 32, 28, and 58% of patients receiving 5-FU, 5-FU+FA, and 5-FU+IFNα, respectively. No differences between the groups were observed for local or distant recurrence. Five-year overall survival (OS) rates were 60.3% (95% confidence interval (CI): 54.3-65.8), 60.4% (54.4-65.8), and 59.9% (53.0-66.1) for 5-FU, 5-FU+FA, and 5-FU+IFNα, respectively. A subgroup analysis in stage II (pT3/4pN0) disease (n=271) revealed that the addition of FA tended to reduce the 5-year local recurrence (LR) rate by 55% and increase recurrence-free survival and OS rates by 12 and 13%, respectively, relative to 5-FU alone.


CONCLUSIONS
Interferon-α cannot be recommended for adjuvant chemoradiotherapy of rectal cancer. In UICC stage II disease, the addition of FA tended to lower LR and increased survival. The addition of FA to 5-FU may be an effective option for adjuvant chemoradiotherapy of UICC stage II rectal cancer.
Kornmann
M
M
Department of General, Visceral, and Transplantation Surgery, University of Ulm, Steinhoevelstrasse, Ulm 89075, Germany. marko.kornmann@uniklinik-ulm.de
Staib
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Wiegel
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Kreuser
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ED
Kron
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M
Baumann
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W
Henne-Bruns
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Link
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D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D055815:Young Adult
D016898:Interferon-alpha; D002955:Leucovorin; D005472:Fluorouracil