May 20, 2009 — In the postsurgical management of malignant melanoma, interferon alfa has been shown to consistently improve relapse-free survival but has not been consistently associated with improved observed overall survival. Because the drug also has significant toxicities, the question for clinicians becomes: Is it worth using?
These facts and this question are posited in an editorial published online May 11 the Journal of Clinical Oncology, which suggests that the question should, in part, be turned over to the patient.
How individual patients value time without relapse and time with toxicity determines the net impact of quality-of-life adjusted survival on alfa interferon, write the editorialists, led by John Glaspy, MD, from the Division of Hematology-Oncology at the David Geffen School of Medicine at the University of California–Los Angeles.
For instance, they note that in 1 study of patients with melanoma who were candidates for interferon therapy, the average patient valued a 4% to 10% improvement in 5-year relapse-free survival highly enough to offset moderate to severe interferon toxicity (J Clin Oncol. 2001;19:812-823).
In short, treatment decisions in high-risk melanoma patients should be made on a case-by-case basis, they suggest.
May 20, 2009 — In the postsurgical management of malignant melanoma, interferon alfa has been shown to consistently improve relapse-free survival but has not been consistently associated with improved observed overall survival. Because the drug also has significant toxicities, the question for clinicians becomes: Is it worth using?
These facts and this question are posited in an editorial published online May 11 the Journal of Clinical Oncology, which suggests that the question should, in part, be turned over to the patient.
How individual patients value time without relapse and time with toxicity determines the net impact of quality-of-life adjusted survival on alfa interferon, write the editorialists, led by John Glaspy, MD, from the Division of Hematology-Oncology at the David Geffen School of Medicine at the University of California–Los Angeles.
For instance, they note that in 1 study of patients with melanoma who were candidates for interferon therapy, the average patient valued a 4% to 10% improvement in 5-year relapse-free survival highly enough to offset moderate to severe interferon toxicity (J Clin Oncol. 2001;19:812-823).
In short, treatment decisions in high-risk melanoma patients should be made on a case-by-case basis, they suggest.
"For the present, peg-IFN-a-2b does not seem to better meet the clinical needs of patients with high-risk melanoma," opine the editorialists.
The new quality-of-life findings come from a major randomized trial of peg-IFN-a-2b, the European Organization for Research and Treatment of Cancer (EORTC) study 18991, which is being conducted by the EORTC but is supported by Schering Plough, the makers of peg-IFN-a-2b. The study is planned for 5 years, but researchers now report interim quality-of-life results. At 3.8 years of median follow-up, the risk for relapse-free survival was reduced by 18% (hazard rate, 0.82; P = .01) in the PEG-IFN-a-2b group, compared with the observation group.
However, compared with the observation group, "significant and clinically meaningful differences" in quality of life occurred with the PEG-IFN-a-2b treatment group, with decreased global health-related quality of life at month 3 (–11.6 points; 99% confidence interval [CI], –8.2 to –15.0) and year 2 (–10.5 points; 99% CI, –6.6 to –14.4).
"Many of the other scales showed statistically significant differences between scores when comparing the 2 arms," write the study authors, headed by Andrew Bottomley, MD, from the Institut Jules Bordet in Brussels, Belgium.
Namely, significant differences between the 2 groups were found in social and role functioning, appetite loss, fatigue, and dyspnea.
However, the editorialists describe these as disappointing in light of the hope that peg-IFN-a-2b would offer an improvement over alfa interferon for high-risk melanoma patients.
"These data are important but disappointing and do not support a conclusion that using peg-IFN-a-2b, at least with the schedule used in EORTC 18991, will either greatly improve the tolerability or significantly increase the feasible duration of treatment for adjuvant interferon in high-risk melanoma," they write.
To date in EORTC 18991, the median duration of treatment is only 12 months, and 31% of patients discontinued treatment with peg-IFN-a-2b because of toxicity. These and other interim clinical results have been reported recently by the investigators (Lancet. 2008;372:117-126).
The interim results from EORTC 18991 indicate that peg-IFN-a-2b administered weekly, with a 2-month induction phase (6 μg/kg per week) followed by maintenance (3 μg/kg per week), improves relapse-free survival but not overall survival in patients with node-positive melanoma, compared with observation alone.
However, the toxicities with peg-IFN-a-2b were similar to those reported in other studies of standard interferon alfa, the editorialists point out. "The specific toxicities reported were similar to those previously reported with adjuvant high-dose interferon in melanoma, including fatigue, hepatotoxicity, and depression," they write.
Nonetheless, the editorialists have not given up hope for peg-IFN-a-2b and EORTC 18991: "It has been pointed out that the follow-up of EORTC 18991 is still early and it is not impossible that, with longer follow-up, this peg-IFN-a-2b regimen will result in improved outcomes, including even improved survival."
The researchers have disclosed no relevant financial relationships.
J Clin Oncol. Published online before print May 11, 2009.
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