Making best use of bowel cancer drugs
A Medical Research Council clinical trial has revealed that treatment for some patients with advanced bowel cancer could be less toxic but no less effective.
Current therapies for patients with the disease, which kills 16,000 people each year in the UK, usually involve two or more drugs in combination from the start. But results of the largest randomised clinical trial ever conducted in the treatment of advanced colorectal cancer, known as FOCUS, run by the Medical Research Council’s Clinical Trials Unit, suggest that starting treatment with a single drug limits toxicity without compromising benefit. The findings are published in The Lancet.
Professor Matt Seymour from the Cancer Research UK Centre at Cookridge Hospital, University of Leeds who led the study explained: “We wanted to find a way to control the symptoms and extend the survival time of people with the most advanced forms of bowel cancer who cannot be cured. We therefore set out to establish the best way to use available drugs to maximise treatment benefit with the fewest unwanted side effects.”
Patients in the FOCUS trial were randomly allocated into three groups, each treated using a different strategy. The surprise finding was that the survival of patients who started with a gentler treatment using just one chemotherapy drug, up-grading to a combination of two drugs only when the first treatment had failed, was no worse than that of patients who received the more toxic two-drug combination chemotherapy from day one.
FOCUS was run by the MRC Clinical Trials Unit, working with more than 60 NHS Cancer Units throughout the UK. 2,135 patients volunteered to take part, and received treatment.
Professor Seymour added "FOCUS offers an important choice for the group of patients with inoperable bowel cancer, informed by the knowledge that a decision to opt for a staged treatment approach, starting with less toxic therapy and keeping active agents in reserve, entails minimal, if any, compromise in survival.”
Professor Mahesh Parmar, Head of the Cancer Group at the MRC Clinical Trials Unit, said “The results of this trial have implications not only for some patients, who may be spared unnecessary treatment, but also for researchers, who might investigate similar policies in other disease sites where a number of drugs are available. The results also provide a basis for investigating new drugs in combination with fluorouracil.”
The findings from FOCUS were reinforced by a second trial published in the same edition of The Lancet. Professor Cornelis Punt, of Radboud University, Nijmegen Medical Centre, Netherlands, led the Dutch Colorectal Cancer Group trial, “CAIRO-1”. Like FOCUS, it compared survival and side-effects in patients receiving a “staged” treatment approach or two-drug combination treatment from the start. They also found no significant difference in survival with the two strategies, but reduced rates of toxic effects in the initial treatment stages for patients in the first group.
Notes to editors:
1. For further information or to arrange an interview, please contact the MRC press office on 020 7637 6011 or press.office@headoffice.mrc.ac.uk.
2. An accompanying commentary also published in the Lancet suggests different initial treatment strategies for different subgroups of patients with advanced colorectal cancer, as follows: 3-drug combination chemotherapy for those with potentially resectable metastases, 3 or 2-drug combination chemotherapy for those with poor performance status, aggressive disease and/or tumour-related symptoms, and single-agent chemotherapy for those with multiple metastases, good performance status and less aggressive disease. (‘Single agent fluorouracil for first-line treatment of advanced colorectal cancer as standard?’ Lancet 2007, 370, 105-7)
3. Further research is still underway in both FOCUS and CAIRO-1 trials. Many of the patients who participated in FOCUS also donated surplus samples of their tumour tissue for research. In a joint project with Cancer Research UK and the Medical Research Council, these samples are now being used to identify molecular markers which may in the future be used to predict, for individual patients, which treatment option will be the most beneficial.
4. Publication details:
FOCUS Trial: Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet 2007; 370: 143-52. Matthew T Seymour, Timothy S Maughan, Jonathan A Ledermann, Clare Topham, Roger James, Stephen J Gwyther, David B Smith, Stephen Shepherd, Anthony Maraveyas, David R Ferry, Angela M Meade, Lindsay Thompson, Gareth O Griffiths, Mahesh K B Parmar, and Richard J Stephens, for the FOCUS Trial Investigators and the National Cancer Research Institute Colorectal Clinical Studies Group.
CAIRO-1 Trial: Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet 2007; 370: 135–42 Miriam Koopman, Ninja F Antonini, Joep Douma, Jaap Wals, Aafke H Honkoop, Frans L G Erdkamp, Robert S de Jong, Cees J Rodenburg, Gerard Vreugdenhil, Olaf J L Loosveld, Aart van Bochove, Harm A M Sinnige, Geert-Jan M Creemers, Margot E T Tesselaar, Peter H Th J Slee, Marjon J B P Werter, Linda Mol, Otilia Dalesio, Cornelis J A Punt.
5. Bowel cancer: There have been major improvements in the diagnosis and treatment of bowel cancer over the past ten years, and the death rate from this disease in the UK is falling: in fact, an 18% fall in the death rate between 1995 and 2005. But despite this progress, bowel cancer is still responsible for over 16,000 deaths each year in the UK, second only to lung cancer.
6. Statistics: In the FOCUS trial, the median survival for those patients who started with combination chemotherapy was 15.9 months. For those who started with a single drug it was 15.1 months. The difference was therefore 0.8 months (95% confidence interval (-2.3 months to +0.8 months)
Ref: MRC/30/07
