CHICAGO-After surgery for lymph-node positive colon cancer, patients with a low risk of recurrence should receive half of the now-recommended standard course of chemotherapy.
The current standard of care for stage III colon cancer is 6 months of oxaliplatin-based adjuvant therapy with FOLFOX (leucovorin, fluorouracil, oxaliplatin) or CAPOX (capecitabine, oxaliplatin), which is also known as XELOX.
However, "oxaliplatin is associated with cumulative dose-dependent neurotoxicity that is debilitating for many patients, both short-term and long-term. Nerve damage, including numbness, tingling, and pain, can persist long after discontinuation of therapy, sometimes permanently. Shorter duration treatment without loss of efficacy would be of benefit to patients and health care resources," said senior author Axel Grothey, MD, an oncologist at the Mayo Clinic Cancer Center in Rochester, Minn., at a press briefing at the 2017 ASCO Annual Meeting, held June 2-6.
Grothey presented data from the International Duration Evaluation of Adjuvant therapy (IDEA) international collaboration of six clinical trials with more than 12,800 patients. He revealed that 3 months of chemotherapy was nearly as effective as 6 months in patients with relatively lower recurrence risk and caused fewer side effects, particularly nerve damage (Abstract LBA1).
IDEA Data Studied
Based on pre-planned analysis of pooled data from these prospective, phase III clinical trials conducted in 12 countries, a shorter, 3-month course of chemotherapy was associated with a less than 1 percent lower chance of achieving disease-free survival (DFS) at 3 years (74.6%) compared to the standard 6-month course (75.5%). In a subset of patients considered at low risk of cancer recurrence, defined as cancer spread to 1 to 3 lymph nodes and not completely through the bowel wall, the difference was even smaller-83.1 percent in patients receiving a 3-month course and 83.3 percent in those receiving a 6-month course.
Patients were followed for a median time of 39 months. The type of chemotherapy regimen selected affected the difference in 3-year DFS between the 3-month and 6-month treatment duration (75.9% vs. 74.8% with CAPOX and 73.6% vs. 76.0% with FOLFOX), although the difference was relatively small.
"Our findings could apply to about 400,000 colon cancer patients worldwide every year. For 60 percent of these patients, who have lower risk for cancer recurrence, 3 months of chemotherapy will likely become the new standard of care," said Grothey.
He noted that patients with higher risk colon cancer should discuss with their doctor whether they are candidates for a shorter course of therapy, taking into consideration their preference, age, and ability to tolerate chemotherapy. "How much are we willing to push patients into 6 months of therapy for little difference in efficacy?" he asked.
The rate of clinically meaningful (grade 2 or higher) nerve damage was substantially less common in patients receiving a 3-month course of chemotherapy (15% with FOLFOX, 17% with CAPOX) compared to a 6-month course (45% with FOLFOX, 48% with CAPOX). He noted that no dose reductions and early discontinuation due to neurotoxicity are common.
Aside from nerve damage, longer chemotherapy also means more diarrhea and fatigue, more doctor appointments, blood draws, and time away from work and social interactions, said Grothey. "For patients with a low risk of recurrence, 3 months of chemotherapy is effective with no compromise in potency, reduced effectiveness, or increased toxicity."
The IDEA data provide a framework for discussions on risks and benefits of individualized adjuvant therapy approaches. "Shorter duration of therapy is associated with remarkable reduction in neurotoxicity," said Grothey. "For low-risk cancers, 3 months duration of oxaliplatin-based therapy is adequate. This applies to about 20,000 patients per year in the U.S. These results should have an immediate impact on care." He noted that 3 months of CAPOX is adequate, whereas a longer duration of FOLFOX might be required.
Grothey added that there was no commercial funding for IDEA, with individual studies supported by public funds and philanthropy.
ASCO Commentary
ASCO Expert Nancy Baxter, MD, PhD, Chief of the General Surgery Department at St. Michael's Hospital in Toronto, Canada, commented: "This is practice-changing work that shows for most people with stage III colon cancer 3 months of treatment provides all the benefits of 6 months of treatment with fewer risks. Less is more.
"We are now able to spare many patients with colon cancer unnecessary side effects of an additional 3 months of chemotherapy without compromising results. This study is an excellent example of how existing treatments can be refined to work even better for patients."
She added: "Although addressing the question, 'Can we give less treatment?' is of major importance to patients and their doctors, it is rare to see this type of study. Given that these questions are unlikely to be of interest to the pharmaceutical industry, federal support for these trials is critical. The pharmaceutical industry is not interested in giving less treatment. This study is a great example of how NIH funding can have a major and immediate impact on the lives of cancer patients."
Richard Schilsky, MD, Chief Medical Officer of ASCO, commented: "This is another step on the road toward personalized cancer treatment based on risk assessment. Not everyone needs adjuvant chemotherapy. Starting next week, colon cancer patients will be prescribed shorter courses of chemotherapy."
Mark L. Fuerst is a contributing writer.