Key message: interferon alpha improves both disease-free survival and overall survival of people with high-risk cutaneous melanoma. Interferon is also valid as a reference standard for future trialsClinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used. No matter how promising a new treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known. of other new treatments.
Cutaneous melanoma is a type of skin cancer that’s on the rise in all Western countries and carries with it a poor chance of survival for those in whom the cancer has spread, with around 10% surviving longer than five years. For those whose cancer has not spread, their outlook after surgery is variable; between 40% and 90% are alive after five years. Interferon alpha is the only drug approved for adjuvant (additional) treatment of high-risk cutaneous melanoma after surgery, but not enough has been known about its benefits for it to be offered as a standard treatment. A new review from the Cochrane Skin Group has brought together evidence from randomisedRandomization is the process of randomly dividing into groups the people taking part in a trial. One group (the intervention group) will be given the intervention being tested (for example a drug, surgery, or exercise) and compared with a group which does not receive the intervention (the control group). controlled trialsA trial in which a group (the ‘intervention group’) is given a intervention being tested (for example a drug, surgery, or exercise) is compared with a group which does not receive the intervention (the ‘control group’). (RCTs) assessing the effects of interferon alpha, as an adjuvant treatmentSomething done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes., on disease-free survival and overall survival in high-risk patients. High-risk patients were defined as those in whom the cancer had spread to the lymph nodes or whose primary tumour was more than one millimeter thick. Eighteen trials with over 10,000 people were included, comparing interferon alpha with observation or other treatments.
What did they find?
- Adjuvant interferon was associated with significantly improved disease-free survival and overall survival
The numbers: Adjuvant interferon was associated with significantly improved disease-free survival (HR (hazard ratio) = 0.83; 95% CI (confidence interval) 0.78 to 0.87, P value < 0.00001) and overall survival (HR = 0.91; 95% CI 0.85 to 0.97; P value = 0.003).
- Whether some treatment features, such as dose and length of time taking it, have an impact of its effectivenessThe ability of an intervention (for example a drug, surgery, or exercise) to produce a desired effect, such as reduce symptoms., or whether subgroups of patients (such as those with our without lymph node involvement) benefit differently, remains unknown
- Side-effects such as fever and tiredness were mostly not severe and went away when the treatment finished
How good was the evidence?
The reviewers judged the evidence to be of high quality, allowing for robust conclusions about the impact of interferon. They were able to perform meta-analyses (combining results) on 10, 345 people in 17 RCTs for disease-free survival and 9927 people from 15 RCTs for overall survival. There was generally low riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of biasAny factor, recognised or not, that distorts the findings of a study. For example, reporting bias is a type of bias that occurs when researchers, or others (e.g. drug companies) choose not report or publish the results of a study, or do not provide full information about a study. in the studies.
Why is this review important?
Hywel Williams, Professor of Dermato-Epidemiology at the University of Nottingham and Co-ordinating Editor of the Cochrane Skin Group, comments:
“It was always unclear to me whether adjuvant therapy with agents like interferon alpha were really worthwhile for people diagnosed with melanoma at high risk of disseminated disease. I knew they could increase disease-free survival, but I was unclear whether they improved overall survival, and if so at what cost in terms of side effects. This review has illustrated to me that interferon alpha not only improves disease-free survival by about 17%, but also overall survival by about 9%. Not a huge benefit granted, but a benefit nevertheless. The studies were fairly similar and I have confidence in these estimates. The side effects of interferon alpha were not severe in the majority and seemed to disappear when treatment was completed. The review has provided important evidence to inform patient choices and has also established a reference standard that other new adjuvant agents can be measured against in future studies.”
This is an important review, then, for people with this life-threatening disease and the doctors treating them and also future trialists. More research is needed to establish which patients are most likely to benefit from this treatment.
Links:
Mocellin S, Lens MB, Pasquali S, Pilati P, Chiarion Sileni V. Interferon alpha for the adjuvant treatment of cutaneous melanoma. Cochrane Database of Systematic ReviewsIn systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. 2013, Issue 6. Art. No.: CD008955. DOI: 10.1002/14651858.CD008955.pub2.
Cochrane summary http://summaries.cochrane.org/CD008955/interferon-for-the-treatment-of-melanoma-patients-after-surgical-removal-of-their-tumour
given the fact that high dose interferon is no “walk in the park”, and the benefits have been unclear, as Dr. Williams said, this is an extremely helpful review to assist us in counseling our patients
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