A phase III randomized trial of adjuvant biochemotherapy (BC) versus interferon-α-2b (IFN) in patients (pts) with high risk for melanoma recurrence

Abstract

8003 Background: High-dose IFN (HDI) is associated with significant toxicity, and its clinical benefit as an adjuvant therapy for melanoma has been often debated. BC is associated with higher response rates than other regimens, but it has never been tested in an adjuvant setting. Methods: We conducted a prospective randomized phase III study comparing the clinical benefit of IFN and BC in pts who had undergone lymphadenectomy within 56 days for melanoma metastatic to regional lymph nodes. Pts were randomized to receive BC (Cisplatin 20 mg/m2 IV [d1–4]; Vinblastine 1.5 mg/m2 IV [d1–4]; DTIC 800 mg/m2 IV [d1]; IFN 5 MU/m2 SQ [d1–5]; IL-2 9 MU/m2 continuous IV infusion [d1–4] every 3 wks for 4 courses) or IFN, and those who were randomized to IFN were further randomized to either HDI (20 MU/m2 IV for 5 d/week for 4 wks and 10 MU/m2 SQ 3 times a wk for 48 wks) or intermediate-dose IFN (IDI) (10 MU/m2 SQ 3 times a wk for 1 year). The primary end points were overall survival (OS) and relapse-free survival (RFS). Using 80% power and 5% significance level, 200 pts would be required to detect the difference in median RFS of 18 vs. 36 months and in OS of 40 vs. 80 months between IFN and BC groups. Results: An interim analysis was performed because of slow accrual. 138 pts were enrolled between 1995 and 2003, with 71, 33 and 33 in the BC, HDI and IDI group, respectively. There were no significant differences in both RFS and OS between HDI and IDI groups. With median follow up of 49.3 months, neither the BC or IFN had reached the median RFS and OS. Log-rank test was used to compare RFS (p=0.96) and OS (p=0.52) between 2 groups. RFS and OS data are presented below. Pts in the BC arm had more grade 3–4 fatigue, nausea, anorexia, capillary leak syndrome, diarrhea and myelosuppression. Conclusions: There were no significant differences in both OS and RFS between the BC and IFN groups. This interim analysis supports terminating this trial before achieving the specified target for patient accrual. Supported in part by Schering-Plough. [Table: see text] [Table: see text]