Duration of adjuvant chemotherapy for stage III colon cancer
Open accessAbstract
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.).
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- Authors
- Grothey, A., Sobrero, A. F., Shields, A. F., Yoshino, T., Paul, J., Taieb, J., Souglakos, J., Shi, Q., Kerr, R., Labianca, R., Meyerhardt, J. A., Vernerey, D., Yamanaka, T., Boukovinas, I., Meyers, J. P., Renfro, L. A., Niedzwiecki, D., Watanabe, T., Torri, V., Saunders, M., Sargent, D. J., Andre, T., & Iveson, T.
- Affiliations
- Mayo Clinic (US)
- From the Divisions of Medical Oncology (A.G.) and Biomedical Statistics and Informatics (Q.S., J.P.M., L.A.R., D.J.S.), Mayo Clinic, Rochester, MN; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Martino-IST, Genoa (A.F. Sobrero), Ospedale Papa Giovanni XXIII, Bergamo (R.L.), and IRCCS Mario Negri Institute for Pharmacological Research, Milan (V.T.) — all in Italy; Karmanos Cancer Institute, Wayne State University, Detroit (A.F. Shields); National Cancer Center Hospital East, Chiba ...
- ORCID
- Grothey, Axel
- Sobrero, Alberto F.
- Shields, Anthony F.
- Yoshino, Takayuki
- Paul, James
- Souglakos, John
- Shi, Qian
- Kerr, Rachel
- Labianca, Roberto
- Meyerhardt, Jeffrey A.
- Yamanaka, Takeharu
- Boukovinas, Ioannis
- Renfro, Lindsay A.
- Niedzwiecki, Donna
- Watanabe, Toshiaki
- Torri, Valter
- Saunders, Mark
- Sargent, Daniel J.
- Iveson, Timothy
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-03-29
- Volume
- 378
- Issue
- 13
- Pages
- 1177-1188
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC6426127
- OpenAlex
- W2795004907
- Cited by
- 1,092
- References
- 16
- Citations by year
- 2026: 96 · 2025: 101 · 2024: 134 · 2023: 123 · 2022: 127 · 2021: 195 · 2020: 174 · 2019: 106 · 2018: 31
- FWCI
- 47.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- Japanese Foundation for Multidisciplinary Cancer Treatment
- Agenzia Italiana del Farmaco (FARM 5RWTWZ)
- Efficacy and Mechanism Evaluation Programme (09/800/34)
- Cancer Research United Kingdom (C1348/A15960)
- National Institute for Health Research, Health Technology Assessment (14/140/84)
- Institut National du Cancer
- Programme Hospitalier de Recherche Clinique en Cancérologie (PHRC2009)
- NIH Clinical Center (U10CA180821, U10CA180835, U10CA180882, U10CA180888)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
- Keywords
- adjuvant chemotherapy, stage III colon cancer, oxaliplatin, FOLFOX, XELOX, treatment duration, non-inferiority, disease-free survival, neurotoxicity, fluoropyrimidine, capecitabine, leucovorin, 5-fluorouracil, health care costs, pooled analysis of randomized trials, T4 tumors
- MeSH terms
- Capecitabine, Oxaliplatin, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Leucovorin, Colonic Neoplasms, Drug Administration Schedule, Female, Fluorouracil, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Nervous System Diseases, Organoplatinum Compounds, Prospective Studies, Proportional Hazards Models, Randomized Controlled Trials as Topic, Chemotherapy, Adjuvant, Clinical Trials, Phase III as Topic, Disease-Free Survival, Medication Adherence, Young Adult, Intention to Treat Analysis
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