ASCO Guideline Recommends Shorter-Course Adjuvant Chemotherapy for Some Patients With Stage III Colon Cancer

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In a clinical practice guideline released April 15, an ASCO Expert Panel outlined the latest recommendations for the duration of adjuvant chemotherapy with a fluoropyrimidine and oxaliplatin for patients with completely resected stage III colon cancer.1 New recommendations were based on the results from trials of 3- and 6-month oxaliplatin-containing chemotherapy leucovorin, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX).

When you separate the low-risk from high-risk patients, there seems to be no added benefit of offering 6-month treatment duration to patients at low risk.
— Christopher Lieu, MD

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“This is the largest investigation into stage III colon cancer that’s ever been performed,” said Expert Panel Co-Chair Christopher Lieu, MD, of the University of Colorado School of Medicine. “It is a remarkable example of international collaborative research. We want to make sure that providers are aware of this new data, which will directly impact the management of their patients.”

Data from six new randomized trials conducted in the scope of the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration were analyzed during guideline development. The IDEA consortium brought together oncology leaders from the United States, Canada, Europe, and Japan, as well as research groups from 12 countries across the world.

Nancy Baxter, MD, FRCSC, FACS, PhD

Nancy Baxter, MD, FRCSC, FACS, PhD

“These studies indicate that there are definitely options for certain patients with colon cancer in terms of the duration of oxaliplatin use,” said Expert Panel Co-Chair Nancy Baxter, MD, FRCSC, FACS, PhD, of the University of Toronto, Canada. “For select groups of patients, we may be able to avoid a lot of the long-term consequences of this treatment by shortening the duration of therapy to 3 months.”

Duration of Oxaliplatin Adjuvant Therapy Varies by Recurrence Risk

Guideline recommendations, informed by an analysis of six randomized trials published in TheNew England Journal of Medicine,2 differentiate between the recommended duration of adjuvant chemotherapy for patients with low-risk vs those with high-risk disease. The guideline defines low-risk patients as having either T1, T2, or T3, and N1 stage tumors and high-risk patients as having T4 and/or N2 stage tumors. It recommends that adjuvant chemotherapy lasting 6 months be offered to patients at high risk of recurrence. For patients at low risk of recurrence, guideline recommendations are less specific and include an option of either 6-month chemotherapy or shorter-duration, 3-month therapy based on an evaluation of potential benefits and adverse events.

Dr. Lieu noted that the Expert Panel wanted to give practitioners the option of offering their patients 3-month adjuvant chemotherapy whenever supported by evidence. “The trial was a noninferiority design, and it did not meet its primary endpoint of disease-free survival because noninferiority was not proven between the 3-month and 6-month treatment groups,” he explained. “However, when you separate the low-risk from high-risk patients, there seems to be no added benefit of offering 6-month treatment duration to patients at low risk.”

Advantages of Shorter-Duration Adjuvant Therapy

Dr. Lieu further emphasized that the potential advantages of shorter-duration adjuvant chemotherapy include a lower incidence of serious adverse events and neurotoxicity. “Oxaliplatin can damage the nerves. When we looked at the rates of grade 2 neurotoxicity in the 3-month arm (12%–14%) vs the 6-month arm (32%–36%), we found a significant difference,” he said. “We need to make sure that we are not harming our patients with prolonged treatment.”

Dr. Baxter agreed that that multiple potential benefits are associated with shorter-duration adjuvant chemotherapy, including “a faster return to normal daily activities, an improvement in both short-term and long-term quality of life, and an overall reduction in the burden of treatment. With the help of these guidelines, we can now identify those patients for whom we can safely reduce therapy,” she said. “This will have direct benefits for the patients and impact the overall use of resources.”

Importance of Shared Decision-Making

The third and final guideline recommendation calls for a shared decision-making approach between the patients and their providers. “This third recommendation is probably the most important in the entire guideline,” Dr. Lieu said. The guideline encourages practitioners to “have an honest conversation with their patients about the potential risks and benefits of treatment,” he said. “This gives the patients the opportunity to achieve the best disease-free survival possible, while also reaching their personal treatment goals.”

Shared decision-making considers patient characteristics and preferences, as well as potential risks and benefits associated with treatment duration. Dr. Lieu noted that the tolerance for chemotherapy can vary widely from one patient to the next, which can be an important factor influencing the decision on adjuvant treatment duration. “There are some patients who really cannot tolerate chemotherapy very well, and, in these cases, the shared decision-making approach becomes very important,” he said. “It gives patients a realistic view of the potential risks and benefits of chemotherapy, helps them achieve their personal goals, and makes them more invested in their care.”

Dr. Baxter agreed that including the patients in treatment decision-making is extremely important. “It is empowering for patients to be able to understand their treatment and its potential beneficial and harmful effects,” she said. “We now have more evidence to help inform that decision.”

Recommendations With a Broad Impact

Both guideline co-chairs are optimistic that these new recommendations will significantly benefit patients facing a stage III colon cancer diagnosis. “We expect the guideline to have the most impact on patients with lower-risk stage III colon cancer, who might receive less chemotherapy as a consequence, which can translate to an improved quality of life and less morbidity,” Dr. Lieu said. “There is also an economic benefit to giving less treatment and, potentially, having to deal with fewer long-term side effects.”

Dr. Baxter is hopeful that these guidelines will not only change practice in the United States and Canada, but that they will have a broad international impact as well, especially in low- and middle-income countries and lower-resource settings. “A reduced burden of treatment for a significant portion of patients with colon cancer can translate to cost savings for health systems, which can then be reinvested to benefit more patients while maintaining treatment effect,” she said. 

DISCLOSURE: For full disclosures of the panel authors, visit


1. Lieu C, Kennedy EB, Bergsland E, et al: Duration of oxaliplatin-containing adjuvant therapy for stage III colon cancer: ASCO Clinical Practice Guideline. J Clin Oncol. April 15, 2019 (early release online).

2. Grothey A, Sobrero AF, Shields AF, et al: Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med 378:1177-1188, 2018.

Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, April 15, 2019. All rights reserved.