Prolonged therapy with pegylated interferon has been found to improve recurrence-free survival in patients with excised stage III melanoma in a randomized phase III trial.
In contrast, survival free of distant metastases was numerically but not statistically significantly better with adjuvant pegylated interferon, and the treatment had no apparent effect on overall survival, Dr. Alexander M. M. Eggermont and his associates reported in the European Organisation for Research and Treatment of Cancer (EORTC) trial 18991 (Lancet 2008;372:117-26).
In an editorial comment that accompanied the report, Dr. Vernon K. Sondak and Dr. Lawrence E. Flaherty wrote that "many patients with melanoma are willing to accept significant toxicity in exchange for a modest improvement in recurrence-free survival, even in the absence of an overall survival effect," (Lancet 2008;372:89-90).
It remains to be seen, however, whether such patients and their physicians will accept 5 years of pegylated interferon treatment "for an absolute benefit in recurrence-free survival of about 6% at 4 years," they noted.
Dr. Eggermont and his colleagues compared the therapy with observation alone in a randomized controlled trial involving 1,256 patients treated at 99 medical centers in 17 countries. All patients had undergone complete excision of stage III melanoma and complete regional lymphadenectomy.
The study was funded by Schering-Plough Research International.
The two study groups were well matched according to disease substage, number of involved lymph nodes, thickness of the primary tumor, and ulceration of the primary tumor. Patients who took interferon received high-dose induction therapy for 8 weeks, followed by once-weekly self-administered subcutaneous injections for an intended duration of 5 years, said Dr. Eggermont, of Erasmus University, Rotterdam, the Netherlands, and his associates.
After a median of 4 years of follow-up, significantly fewer recurrences had developed in the interferon group than in the observation group, with a 6.7% absolute difference in estimated rates of recurrence-free survival. The therapy's benefit was seen early in the course of treatment and remained at a consistent level throughout the study, the investigators said.
However, there was no difference in overall survival between patients who took pegylated interferon and those who did not.
The drug was most effective in patients who had microscopic rather than palpable nodal disease, patients whose involvement was limited to one lymph node, and in patients with ulcerated rather than nonulcerated tumors. These groups accounted for approximately 40% of the treated patients.
One-third of the study subjects who took interferon discontinued the drug because of toxicity. The most common adverse effects were fatigue and depression, which were reported in 25% and 16% of patients, respectively. Anorexia, liver function abnormalities, myalgia, headache, nausea, and fever also were reported.
In their editorial comment, Dr. Sondak of H. Lee Moffitt Cancer Center, Tampa, and Dr. Flaherty of Karmanos Cancer Institute, Detroit, said that a 4-year follow-up "is too short for final conclusions." Further follow-up and more clinical trials are needed. However, they added, "for the large group of patients with melanoma found in their sentinel node, we believe this regimen will be an attractive alternative to high-dose interferon."
Dr. Eggermont, Dr. Sondak, and Dr. Flaherty have all been paid consultants for Schering-Plough.