Postoperative irinotecan in resected stage II-III rectal cancer: final analysis of the French R98 Intergroup trial†.
BACKGROUND
The R98 trial explores the addition of irinotecan to a 5-fluorouracil (5-FU) plus leucovorin (5-FU/LV) adjuvant regimen in optimally resected stages II-III rectal cancers. We report the updated long-term results. Disease-free survival (DFS) was the primary end point.
Between March 1999 and December 2005, 357 patients were randomized: 178 in 5-FU/LV and 179 in LV5-FU2 + irinotecan arm. The trial was stratified by control arm: Mayo Clinic regimen or LV5-FU2 regimen.


RESULTS
Three hundred and fifty-seven randomized patients were evaluable for efficacy. With a follow-up of 156 months, the DFS was in favour of experimental arm but did not reach statistical significance [hazard ratio (HR) = 0.80, P = 0.154]. The same was observed for overall survival (OS) (HR = 0.87, P = 0.433). The 5-year DFS was 58% in the control arm and 63% in the experimental arm. The 5-year OS was 74% in the control arm and 75% in the experimental arm. Patients allocated to the experimental arm had more grade 3-4 neutropenia when compared with the LV5-FU2 arm (33% versus 6%, P = 0.03), but not when compared with the Mayo Clinic arm (33% versus 36%, P = 0.84). Grade 3-4 diarrhoea tended to be higher in the experimental arm, but analyses stratified by control arm or by radiotherapy failed to show significant differences across strata (test for interaction P = 0.44).


CONCLUSIONS
Even though a benefit of irinotecan in subgroups of patients cannot be excluded, due to early termination and lack of power, the study does not support the addition of irinotecan to 5-FU/LV in routine in patients with resected stage II-III rectal cancer.
Oncology Unit, Diaconesses Croix Saint Simon Hospital, Paris. Electronic address: cdelbaldo@hopital-dcss.org.
C
C
Delbaldo
Digestive Oncology Unit, ICM Val D'Aurelle, Montpellier.
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M
Ychou
Radiotherapy Unit, Departemental Hospital Center, La Roche Sur Yon.
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A
Zawadi
Oncology Unit, René Gauducheau Center, St-Herblain.
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JY
Douillard
Oncology Unit, Saint-Antoine Hospital, GERCOR, and UMPC University Paris VI, Paris.
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André
Oncology Unit, Paul Papin Center, Angers.
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Guerin-Meyer
Hepatogastroenterology and Digestive Oncology Unit, Université Paris V, Europeen Georges Pompidou Hospital, Paris.
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Rougier
Radiotherapy Unit, Jean-Bernard Center, Le Mans.
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Dupuis
Digestive Unit, Departemental Hospital Center, La Roche sur Yon.
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Faroux
Radiotherapy Unit, Henri Mondor Hospital, Créteil, France.
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Jouhaud
International Development Drug Institute (IDDI), Louvain-la-Neuve, Belgium.
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Quinaux
International Development Drug Institute (IDDI), Louvain-la-Neuve, Belgium.
M
M
Buyse
Oncology Unit, Paul Strauss Center, Strasbourg, France.
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Piedbois
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D018572:Disease-Free Survival; D057239:Early Termination of Clinical Trials; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005602:France; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
5-fluorouracil; adjuvant chemotherapy; irinotecan; phase III; rectal cancer; safety