NIHR | March 2018 |Three-month course of chemotherapy as effective as six months following surgery for bowel cancer
NIHR and MRC in partnership have funded international clinical trial, which has evaluated the effectiveness of a three-month course of adjuvant oxaliplatin/fluoropyrimidine combination chemotherapy for colorectal cancer versus the standard six-month treatment regimen. The trial’s findings indicate that the shorter duration treatment leads to similar survival outcomes with better quality of life for patients and therefore might represent a new standard of care.
The research team led by the Cancer Research UK Clinical Trials Unit in Glasgow, recruited more than 6,000 patients with high-risk stage II or stage III colorectal cancer from 244 centres across Europe, Australia and New Zealand. The participants in the trial received either a three or six month course of chemotherapy and were followed up for a minimum of three years.
Three years later, 76.7% of patients who received treatment over three months were disease free compared to 77.1% of patients treated over six months. Patients treated over three months had fewer side effects and reported a better quality of life as well as reduced peripheral neuropathy.
Chief Investigator Dr Tim Iveson, Consultant Medical Oncologist at University Hospital Southampton NHS Foundation Trust and Honorary Associate Professor at the University of Southampton, said: “Bowel cancer is the fourth most common cancer in the UK with 41,000 new cases each year. Bowel cancer can be cured by surgery and chemotherapy. Approximately 2,500 patients per year currently receive up to six months of post-operative chemotherapy. Reducing chemotherapy duration to three months will save the NHS £5000 per patient – a total saving to the NHS of £12.5 million pounds per year.
Dr Iveson added: “The impact on patients is important, as by having a shorter course of chemotherapy patients have fewer side effects. Based on these results, three months of post-operative chemotherapy should be considered as the new standard care for many patients with bowel cancer.”
The full unedited news item is available from NIHR here
6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment.
The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing.
6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1–78·2) for the 3 month group and 77·1% (75·6–78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909–1·114, test for non-inferiority p equal to 0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group).
In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care.
Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK.
Iveson, T. J., et al | 2018 | 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial | The Lancet Oncology | Vol. 19 | 4 | P.562–78
The full article can be read in The Lancet here