NICE 2002/ 031
Issued: 07 June 2002
PRESS RELEASE
The National Institute for Clinical Excellence (NICE) published guidance on the use of three drugs used for people with advanced colorectal cancer in March this year. None of the drugs the Institute was asked to appraise are a cure for advanced colorectal cancer. They are other options available, including established chemotherapy regimes (proven to extend life and slow disease progression), surgery, radiation therapy, symptom control and psychosocial support.
The NICE guidance does not deny patients with advanced disease access to these drugs. It is however clear about where the evidence supports the use of these treatments and about their limitations. NICE estimates its guidance will increase NHS spending on these drugs by about £41 million each year. Where clinicians consider it is appropriate to prescribe these drugs for individual patients in line with the NICE guidance, NHS organisations in England and Wales are under a direction to make the necessary resources available, thus ending previous postcode prescribing.
NICE guidance will increase access to one drug (oxaliplatin) for patients whose cancer has spread to their liver and could, if the tumours were shrunk using it, become operable. NICE guidance is also clear that another of these drugs (irinotecan) should be added into the established chemotherapy treatment, when the disease progresses.
Because of the current uncertainty surrounding the value of these treatments as a first line therapy the Medical Research Council (MRC) established the FOCUS trial. NICE guidance actively encourages oncologists who feel that first line treatment is an option for their patient to enrol the patient (following discussion and consent) in this trial - this will ensure that patients are treated appropriately and data is collected to determine the true value of these treatments. The MRC FOCUS trial is due to report in 2004, and NICE will be reviewing its guidance on these drugs in 2005.
During the development of NICE guidance the Institute received evidence from, heard expert testimony from, and consulted with oncologists and 17 national groups representing the full range of health professionals who provide care to people with colorectal cancer. Similarly we heard from and consulted with patients and the national groups that represent them. Each of these organisations had access to the full evidence base (including an independent review of the world wide data), and were provided with the opportunity to appeal if they considered that the NICE guidance was perverse. None of these organisations chose to appeal against the final guidance issued to the NHS.
Anne-Toni Rodgers, Communications Director, stated: "Rather than deny treatment the NICE guidance will increase access to oxaliplatin and irinotecan for those patients across England and Wales who will benefit from their use. The guidance will increase NHS spending on these drugs by around £41 million each year. Patients with liver tumours may be treated with oxaliplatin first line to shrink the tumours enough for surgery; and irinotecan may be added to established chemotherapy as the disease progresses, finally we have actively encouraged doctors to enrol NHS patients who they believe would benefit from either of these drugs as a first line treatment in ongoing clinical trials that the MRC established because of existing uncertainty surrounding such first line treatment. NICE will be considering the results of this trial when it reviews its guidance in 2005.
"The kind of decisions the Institute is asked to make are amongst the most difficult in public life. Those who form our advisory committees are acutely aware of the responsibility they carry and they form their recommendations with great care. They deserve credit for the calm and considered way in which they analyse and interpret the evidence before them, notwithstanding the storms of publicity and promotion which sometimes surround the medicines we ask them to evaluate".
Ends
Notes for editors
Advanced colorectal cancer and current treatment.
- Colorectal (bowel) cancer is common. Every year 57 out of every 100,000
people will be diagnosed and around 15,000 people in England and Wales will
die as a result of the disease. It occurs in about the same proportion of
men as women, is rare in people aged under 40 years and approximately 41%
of patients are above 75 years of age, (half of deaths from colorectal cancer
occur in this age group).
- Colorectal cancer is described as advanced if it has either metastasised
or is unlikely to be cured by surgery. Metastasised means that cancer cells
from the bowel have travelled to other parts of the body (such as the liver)
where they multiply as a secondary cancer.
- Approximately 55% people diagnosed with colorectal cancer have the advanced
disease. Half of those diagnosed who do not have advanced disease when diagnosed
develop it at a later stage. Most people diagnosed with advanced colorectal
cancer live between 6 and 9 months although 1 in 20 people live for 5 years.
- None of the drugs the Institute was asked to appraise are a cure for
this cancer. They are one option for treatment used, in sequence with
other interventions including alternative chemotherapy regimens, surgery,
radiation therapy, symptom control and psychosocial support.
Not all people are well enough to tolerate the side effects of chemotherapy drugs. Those, who are fit enough, are usually treated with chemotherapy as first-line or second-line therapy. Chemotherapy agents may be used on their own in combination with other drugs, with surgery and/or with radiotherapy. When chemotherapy is used as a first-line therapy it means that it is the first treatment used to treat the cancer. Second-line therapy means that it is used after an initial treatment has failed.
- Typically, a combination drug treatment (called 5FU/FA) is used as first
line chemotherapy for advanced colorectal cancer. Compared with best supportive
care, 5FU-based regimens, administered on diagnosis of advanced disease, increase
median survival from 5-9 months to between 7.5 and 14 months and they increase
median symptom-free survival from 2 months to 10 months without reducing quality
of life.
In patients who do not initially respond, or in those whose disease has become resistant, second-line chemotherapy is often used.
The 5FU/FA treatments have been available for a number of years and are relatively inexpensive.
- A number of people present with advanced colorectal cancer that is confined to the liver. Surgical removal of single or occasionally multiple liver tumours may have a significant effect on long-term survival. Liver metastases that are initially considered unsuitable for surgical treatment may become resectable (i.e. suitable for surgical removal) by chemotherapy that shrinks the liver tumours.
- Oxaliplatin - liver metastases: The Committee considered evidence
on the clinical effectiveness of oxaliplatin in combination with 5FU/FA for
patients with tumours confined to the liver that may be shrunk enough by the
chemotherapy to allow surgical removal. The Committee was persuaded by the
possibility that this treatment could provide a significant survival benefit
for a proportion of patients, extending possibly to a cure.
On this basis, the Committee considered oxaliplatin to be clinically and cost effective in this group of patients.
The NICE guidance on this sub group of patients reflected the Committee's considerations and states:
-
Irinotecan and oxaliplatin - first line treatment.
Neither of these drugs is licensed for first line treatment as a monotherapy and the Committee saw no evidence to support this use.Chemotherapy with 5FU regimens alone usually delays disease progression and/or recurrence of symptoms by about 6 months and also improves quality of life. They increase survival from 5-9 months to between 7.5 and 14 months and they increase symptom-free survival from 2 months to 10 months without reducing quality of life.
If irinotecan or oxaliplatin were to be used as a first line treatment they would have to be added to the standard 5FU therapy.
It was suggested that adding either of these drugs to 5 FU could increase survival by about 2.6 months and that these drugs were therefore cost effective. However there was concern about the robustness of the stated additional 2.6 months survival as this figure was extrapolated from a trial containing at least 50% crossover in each study arm (an effect which reduces the reliability of results of the trial). The committee concluded therefore that it was not possible to reasonably conclude that reported survival gains were purely attributable to the irinotecan or oxaliplatin in combination with 5FU/FA.
In addition, randomised control trials demonstrated no survival advantage for therapy with oxaliplatin in combination with 5FU/FA. That is the length of life remains unchanged.
It was accepted that both the treatments in combination with 5FU might delay the progression of the disease by approximately 2-3 months. That is the spread of the disease may delayed for 2-3 months
Because of insufficient number of patients in some of the trials it was difficult to distinguish between irinotecan and oxaliplatin combination therapy when considering likely treatment benefits.
On the balance of these considerations, the additional benefits of treatment were not seen to justify the increased cost. The Committee also noted that, in the absence of these treatments, other treatment options would be available to patients, most notably, first-line treatment with 5FU/FA (above) followed by the second-line use of irinotecan monotherapy.
NICE Guidance
This is a summary of the guidance, the full evidence base and the detailed considerations of the Committee. The Assessment Report and full guidance are available on the NICE web site.
Oxaliplatin should be considered for use as first-line therapy, in combination with 5FU/FA, in advanced colorectal cancer in patients with metastases that are confined solely to the liver and may become resectable ('down staged') following treatment.
The NICE guidance reflected the Committee's consideration and states:
On the balance of clinical and cost-effectiveness, neither irinotecan nor oxaliplatin in combination with 5-fluorouracil and folinic acid (5FU/FA) are recommended for routine first-line therapy for advanced colorectal cancer.
