Brown University News Bureau

The Brown University News Bureau

1995-1996 index

Distributed May 20, 1996
Contact: Mark Nickel

An Eastern Cooperative Oncology Group study

Quality-of-life/quantity-of-life analysis shows treatment with interferon alfa-2b is effective for high-risk malignant melanoma patients

Using Q-TWiST (Quality-adjusted Time Without Symptoms and Toxicity), a statistical technique that brings quality of life factors into the analysis of treatment regimens, researchers of the Eastern Cooperative Oncology Group have demonstrated that the benefits of interferon treatment outweigh its significant side effects.

PHILADELPHIA -- The benefits of high-dose interferon alfa-2b therapy outweigh its side effects when the treatment is given to patients after surgery for melanoma, according to research presented at a meeting of the American Society of Clinical Oncology. This new finding is the result of an analysis that uses Q-TWiST (Quality-adjusted Time Without Symptoms or Toxicity) analysis, an innovative statistical technique that goes beyond the standard survival analysis used to evaluate most new cancer treatments. In a Q-TWiST analysis, the usefulness of a new cancer therapy is evaluated by simultaneously assessing both its survival benefits and its possible negative quality-of-life impact due to side effects.

Previously, researchers from the Eastern Cooperative Oncology Group (ECOG) had demonstrated that interferon alfa-2b provides effective treatment for high-risk malignant melanoma when given in high doses for one year as an adjuvant treatment following surgery. In a clinical trial involving 280 patients, ECOG investigators found that patients who received interferon alfa-2b after surgery lived longer and experienced fewer relapses of their cancer than patients who received no adjuvant therapy. A 12-month improvement in the median survival time was demonstrated for patients receiving interferon alfa-2b therapy. It was also reported that patients receiving the high-dose interferon alfa-2b therapy experienced significant side-effects that consisted mainly of flu-like symptoms. This new research applied the Q-TWiST methodology to the ECOG study data to determine the degree of benefit associated with interferon alfa-2b treatment after adjusting for the side effects that the patients experienced.

"Since many cancer therapies are associated with side effects that can significantly impact quality of life, the question often arises whether the clinical benefit derived from a treatment outweighs its associated side-effects," said Dr. John M. Kirkwood, principal investigator of the ECOG study. "This is a key issue now that we have an adjuvant treatment for high-risk malignant melanoma which provides significantly increased survival, albeit with side effects."

To perform the Q-TWiST analysis, the investigators first determined how much time patients spent on average in three separate health states: 1) time with interferon alfa-2b side-effects; 2) time free from side effects and free from cancer relapse; and 3) time following cancer relapse. Next, these health states were weighted according to the quality of life associated with them, and the quality-adjusted survival time was computed by adding the three weighted health state durations. The results indicated that regardless of the quality-of-life weightings used, the benefits of interferon therapy offset its side effects in terms of quality-adjusted survival. This benefit was especially significant for patients who considered interferon side-effects to be manageable but disease relapse to be devastating.

"The Q-TWiST methodology can be used to evaluate the usefulness of treatments for cancers other than malignant melanoma," said Bernard F. Cole, principal investigator of the Q-TWiST study. "The Q-TWiST analysis provides a tool that can be used to evaluate the trade-off between clinical benefit and side effects of new therapies, making it easier for practicing physicians to interpret clinical trial data with respect to an individual patient's situation. When Q-TWiST was applied to the ECOG melanoma study, the clinical benefit of interferon alfa-2b therapy was shown to outweigh the side effects of treatment."

Paper: A Quality-of-Life-Adjusted Survival Analysis of Interferon Alfa-2b Adjuvant Treatment for High-Risk Resected Cutaneous Melanoma: An Eastern Cooperative Oncology Group Study

Participants: B.F. Cole, Brown University, Providence, RI; R.D. Gelber, Harvard University, Boston, MA; J.M. Kirkwood, University of Pittsburgh, Pittsburgh, PA; A. Goldhirsch, Ospedale Civico, Lugano, Switzerland; E. Barylak, Manitowoc Clinic, Manitowoc, WI; E. Borden, University of Maryland, Baltimore, MD

ASCO Presentation: Aron Goldhirsch, M.D., Ospedale Civico, Lugano, Switzerland; Tuesday, May 21, 1996; malignant melanoma session; 1:00-4:45 p.m.

Contact: Bernard F. Cole, Ph.D. 401/863-9188

Support: In part by American Cancer Society grant PBR-53 and by Schering Corporation, Kenilworth, N.J.