Reducing the Impact of Treatment Without Decreasing the Chance of Cure: Examining Duration of Adjuvant Chemotherapy for Colon Cancer

15 Aug 2018 2:10 PM | Brandon Davenport

Digest Commentator: Maclean Thiessen MD MN BSc FRCPC, Breast and GI Medical Oncology Fellow, Department of Oncology, Faculty of Medicine, University of Calgary, Calgary, Alberta; Scholar in Residence, The College, University of Calgary, Calgary, Alberta

Digest Editor:  Mary Ann O’Brien, PhD, Department of Family and Community Medicine, University of Toronto

In general, chemotherapy is administered for one of two reasons: 1) As part of a strategy to cure cancer or 2) as part of a strategy to control disease and improve survival and/or symptoms for patients whose malignancy cannot be cured. In many types of cancer, when chemotherapy is being used as part of a curative strategy, the most important part of the treatment strategy is surgery – with chemotherapy

being given either before or after surgery to improve the chance that the cancer will not come back. Colon cancer patients who have disease limited to the colon, but have involvement of regional lymph nodes, are usually offered chemotherapy after surgery. Chemotherapy has been demonstrated to improve survival by about one third in patients with lymph node positive colon cancer (1, 2). Historically, chemotherapy is given for a total of six months to these patients. While chemotherapy can substantially reduce the risk of recurrence, receiving chemotherapy for half a year can have a substantial impact on a person’s life for many reasons including cumulative toxicity and prolonged time away from work.

At the 2017 American Society of Clinical Oncology (ASCO) meeting, prospectively-designed pooled analysis of individual patient data from six large clinical trials was presented (3). In this analysis, patients with node positive, resected colon cancer had been randomized to receive either three or six months of standard post-surgical chemotherapy. At 39 months median follow-up, the shorter three-month treatment was found to be non-inferior(4) to the six-month treatment. In simple terms, non-inferiority means that, statistically, the three-month duration of treatment was found to be no worse than the six- month duration of treatment. In a subset analysis, three months of treatment was found to be inferior to six months, with three-year disease free survival decreased by 1.7% (95% CI = -4.3% to 0.9%) from 64.4% to 62.7% for patients who received three months of chemotherapy compared to those who received six months. Six months of treatment compared to three months of treatment was associated with higher rates of neurotoxicity, severe enough to interfere with activities of daily living.

Why I liked the article: Less toxicity and faster completion of treatment will undoubtedly help to lessen the psycho-social impact of the colon cancer experience for many patients. While the results of this study have not matured, and other studies exploring three versus six months in this same population are underway, this report is exciting. These early results suggest that the biggest benefit of chemotherapy in this population occurs in the first three months, after which there may be an opportunity to further tailor treatment around patient’s pathological risk features and psycho-social needs.


1. Andre T, de Gramont A, Study Group of Clinical Research in Radiotherapies Oncology OMRG. An overview of adjuvant systemic chemotherapy for colon cancer. Clin Colorectal Cancer. 2004;4 Suppl 1:S22-8.

2. Andre T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, et al. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: Updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015;33(35):4176-87.

3. Shi Q, Sobrero A, Shields A, Yoshino T, Paul J, Taieb J, et al., editors. Prospective pooled analysis of six phase III trials investigating duration of adjuvant (adjuv) oxaliplatin-based therapy (3 vs 6 months)

for patients (pts) with stage III colon cancer (CC): The IDEA (International Duration Evaluation of Adjuvant chemotherapy) collaboration. American Society of Clinical Oncology; 2017; Chicago, Illinois, USA. J Clin Oncol. 2017;35 (suppl; abstr LBA1).

4. Mauri L, D'Agostino RB, Sr. Challenges in thedesign and interpretation of noninferiority trials. N Engl J Med. 2017;377(14):1357-67.

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