Should Dukes' B patients receive adjuvant therapy? A statistical perspective.
The benefit of adjuvant therapy, such as 5-fluorouracil (5-FU) combined with leucovorin, is a matter of debate for patients with Dukes' B colon cancer. Several approaches have been taken to address this issue. Initially, studies were conducted to assess treatment benefits in both Dukes' B and Dukes' C patients. These studies identified an overall benefit of adjuvant treatment and enrolled enough Dukes' C patients to determine a treatment benefit for adjuvant 5-FU/leucovorin in this subpopulation. However, the individual studies were insufficiently powered to detect a treatment benefit in Dukes' B patients. An analysis of four separate studies (National Surgical Adjuvant Breast and Bowel project) compared the benefit of adjuvant treatment in Dukes' B patients with that in Dukes' C patients and showed similar relative reductions in mortality and disease-free survival in Dukes' B and in Dukes' C patients. The Liver Infusion Meta-Analysis Group also reported similar relative benefits from a portal vein infusion of 5-FU-based chemotherapy in Dukes' B and Dukes' C patients. The International Multicenter Pooled Analysis of Colon Cancer Trials B2 study, which combined data from patients with Dukes' B colon cancer in five separate trials, failed to show a statistically significant benefit of adjuvant 5-FU/leucovorin compared with surgery alone. We review the advantages and limitations of different approaches to detect treatment benefits in patients with Dukes' B colon cancer, and we argue that there is a need for a meta-analysis of all adjuvant trials to reliably address this question.
Buyse
M
M
International Institute for Drug Development, Brussels, Belgium.
Piedbois
P
P
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D015201:Meta-Analysis as Topic; D015337:Multicenter Studies as Topic; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D013223:Statistics as Topic
D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil