Clinicians should be aware that the high-dose regimens have significant toxic effects.
Evidence (high-dose interferon alpha-2b):
A multicenter, randomized, controlled study (EST-1684) compared a high-dose regimen of interferon alpha-2b (20 mU/m2 of body surface per day given intravenously 5 days a week for 4 weeks, then 10 mU/m2 of body surface per day given subcutaneously 3 times a week for 48 weeks) with observation.[Level of evidence: 1iiA]
This study included 287 patients at high risk of recurrence after potentially curative surgery for melanoma (patients with melanomas thicker than 4 mm without involved lymph nodes or patients with melanomas of any thickness with positive lymph nodes).
Patients who had recurrent melanoma involving only the regional lymph nodes were also eligible.
At a median follow-up of 7 years, this trial demonstrated a significant prolongation of RFS (P = .002) and OS (P = .024) for patients who received high-dose interferon.
The median OS for patients who received the high-dose regimen of interferon alpha-2b was 3.8 years, compared with 2.8 years for those in the observation group.
A subset analysis of the stage II patients failed to show any RFS or OS benefit from high-dose interferon. Because the number of stage II patients was small in this subset analysis, it is difficult to draw meaningful conclusions from this study for this specific group.
A multicenter, randomized, controlled study (EST-1690) conducted by the same investigators compared the same high-dose interferon alpha regimen with either a low-dose regimen of interferon alpha-2b (3 mU/m2 of body surface per day given subcutaneously 3 times per week for 104 weeks) or observation. The stage entry criteria for this trial included patients with stage II and III melanoma. This three-arm trial enrolled 642 patients.[Level of evidence: 1iiA]
At a median follow-up of 52 months, a statistically significant RFS advantage was shown for all patients who received high-dose interferon (including the clinical stage II patients) when compared with the observation group (P = .03).
No statistically significant RFS advantage was seen for patients who received low-dose interferon when compared with the observation group.
The 5-year estimated RFS rate was 44% for the high-dose interferon group, 40% for the low-dose interferon group, and 35% for the observation group.
Neither high-dose nor low-dose interferon yielded an OS benefit when compared with observation (HR, 1.0; P = .995).