Six months of oxaliplatin-based chemotherapy has been the standard adjuvant therapy for stage III colon cancer since 2004, however, the neurotoxicity of oxaliplatin sparked research into whether three months of therapy provided the same benefit but with reduced side effects
The debate on whether to shorten adjuvant chemotherapy for colon cancer from six to three months was debated in a special session at the ESMO 2017 Congress in Madrid.
“Is three months of chemotherapy enough in the adjuvant treatment of colon cancer? This is the main controversy in this debate,” according to ESMO spokesperson Professor Alberto Sobrero, Head of the Medical Oncology Unit at Ospedale San Martino in Genova, Italy, co-chair of the Special Session and Scientific Co-Chair of the Congress. "This debate is a practice changing one and the session will give much more clarity on how clinicians should now treat their patients."
Six months of oxaliplatin-based chemotherapy has been the standard adjuvant therapy for stage III colon cancer since 2004. However, the neurotoxicity of oxaliplatin sparked research into whether three months of therapy provided the same benefit but with reduced side effects.
Six randomised phase III trials have been conducted worldwide comparing three versus six months of chemotherapy with FOLFOX or CAPOX. The IDEA study was a pooled analysis of the 12,834 patients enrolled in the six trials. It showed that six months gave less than 1% added benefit over three months when all patients and both types of chemotherapy were included in the analysis.
Investigators of the four most mature trials (SCOT, TOSCA, ACHIEVE, IDEA-FRANCE) presented their results during the congress session. Expert interpretation was given by a clinician and a statistician. Gastrointestinal cancer specialist Professor Andrés Cervantes, Chair of the ESMO Educational Committee, member of the ESMO Guidelines Committee and session co-chair, discussed how the latest data will impact ESMO Clinical Practice Guidelines on Early Colon Cancer, which are set to be updated in 2018. Members of the panel were asked to vote for three or six months of treatment in a variety of clinical scenarios.
"The common-sense conclusion from the IDEA study is that it's not worth going through the toxicity and inconvenience of six months to gain less than 1% efficacy," said Sobrero. "Especially considering that the toxicity is cut by at least 50% with the three-month regimen."
"Statistically, three months of treatment was slightly inferior to six months in the overall study population of stage III patients," added ESMO spokesperson Professor Eric Van Cutsem, main author of the ESMO consensus guidelines for the management of patients with metastatic colorectal cancer, Head of Digestive Oncology, University Hospitals Leuven, Belgium. "However, the clinical conclusion, given the reduction in neurotoxicity with a shorter duration of treatment, was that three months is almost identical to six months."
Two additional analyses revealed unexpected findings. First, for high risk stage III patients (N2 or T4) the difference in efficacy widens in favour of six months. Second, the results differ according to the type of chemotherapy. CAPOX is equally effective at three or six months, independently of the patient's level of risk. Six months of FOLFOX is more effective than three months.
"While overall there are minor differences in efficacy between three and six months, high risk patients should receive six months of chemotherapy and CAPOX should be preferred over FOLFOX,” added Sobrero.
"In low-risk patients the difference was so minor that the clinical conclusion is that three months of oxaliplatin-based chemotherapy is as good as six months," said Van Cutsem. "Although statistically the difference is small, this makes a huge clinical difference to patients with the reduction in neurotoxicity."
Regarding the standard of care for adjuvant chemotherapy in stage III colon cancer, Van Cutsem said: "In high risk patients six months remains the standard, but in low risk patients three months should become the new standard duration of treatment."
Van Cutsem confirmed that this is the strategy he uses with his stage III colon cancer patients. He said: "In high risk stage III patients we give six months of FOLFOX - unless the patient has neurotoxicity, in which case we stop oxaliplatin but continue with 5FU for a total duration of six months. In patients with low risk tumours, we give three months of FOLFOX."
Sobrero said most patients prefer the three-month option which gives much lower toxicity for very little loss in efficacy. He said: "Every now and then I see a patient who does not want to lose even 1% of efficacy and wants six months of chemotherapy. This is just one of the fascinating aspects of implementing the data from the IDEA study."