Duration of Adjuvant Chemotherapy for Stage III Colon Cancer.

Abstract

BACKGROUND:

Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures.

METHODS:

We performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12.

RESULTS:

After 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority).

CONCLUSIONS:

Among patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.).

• Authors: Axel Grothey, Alberto F Sobrero, Anthony F Shields, Takayuki Yoshino, James Paul, Julien Taieb, John Souglakos, Qian Shi, Rachel Kerr, Roberto Labianca, Jeffrey A Meyerhardt, Dewi Vernerey, Takeharu Yamanaka, Ioannis Boukovinas, Jeffrey P Meyers, Lindsay A Renfro, Donna Niedzwiecki, Toshiaki Watanabe, Valter Torri, Mark Saunders, Daniel J Sargent, Thierry Andre, Timothy Iveson
• Journal: The New England journal of medicine (N Engl J Med) Vol. 378 Issue 13 Pg. 1177-1188 (Mar 29 2018) ISSN: 1533-4406 [Electronic] United States
• PMID: 29590544 (Publication Type: Comparative Study, Equivalence Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Organoplatinum Compounds
• Oxaliplatin
• Capecitabine
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Capecitabine (administration & dosage, adverse effects)
• Chemotherapy, Adjuvant
• Clinical Trials, Phase III as Topic
• Colonic Neoplasms (drug therapy, pathology)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Intention to Treat Analysis
• Leucovorin (administration & dosage, adverse effects)
• Male
• Medication Adherence
• Middle Aged
• Neoplasm Recurrence, Local
• Neoplasm Staging
• Nervous System Diseases (chemically induced)
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Oxaliplatin
• Proportional Hazards Models
• Prospective Studies
• Randomized Controlled Trials as Topic
• Young Adult