RANDOMIZED PHASE-III TRIAL OF TREATMENT WITH HIGH-DOSE INTERLEUKIN-2 EITHER ALONE OR IN COMBINATION WITH INTERFERON ALFA-2A IN PATIENTS WITH ADVANCED MELANOMA

被引:149
作者
SPARANO, JA
FISHER, RI
SUNDERLAND, M
MARGOLIN, K
ERNEST, ML
SZNOL, M
ATKINS, MB
DUTCHER, JP
MICETICH, KC
WEISS, GR
DOROSHOW, JH
ARONSON, FR
RUBINSTEIN, LV
MIER, JW
机构
[1] UNIV TEXAS,HLTH SCI CTR,AUDI L MURPHY VET ADM MED CTR,SAN ANTONIO,TX 78284
[2] NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892
[3] LOYOLA UNIV,MED CTR,MAYWOOD,IL 60153
[4] UNIV CALIF SAN FRANCISCO,MED CTR,SAN FRANCISCO,CA 94143
[5] CITY HOPE NATL MED CTR,DUARTE,CA 91010
[6] TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111
[7] HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110
关键词
D O I
10.1200/JCO.1993.11.10.1969
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To compare the response rate, survival, and toxicity of treatment with high-dose intravenous (IV) bolus interleukin-2 (IL-2) plus interferon alfa-2a (IFN-α) with high-dose IL-2 alone in patients with advanced melanoma in a randomized phase III trial design. Patients and Methods: Eighty-five patients with advanced melanoma were randomly assigned to receive IL-2 6 x 106 U/m2 per dose every 8 hours as tolerated for a maximum of 14 doses on days 1 through 5 and 15 through 19, or IL-2 4.5 x 106 U/m2 per dose, plus IFN-α 3 x 106 U/m2 using an identical schedule. A planned interim analysis was performed after 85 patients were entered, which forms the basis for this report. Results: Partial response (PR) occurred in two of 44 patients (5%; 95% confidence interval, 1% to 15%) receiving IL-2 alone, compared with four of 41 patients (10%; 95% confidence interval, 3% to 23%) receiving IL-2/IFN- α (P = .30). There were no complete responses (CRs). The median duration of response was 11.5 months (range, 2.0 to 15.7+). There was no significant difference in the median survival duration for patients receiving IL-2 alone (10.2 months) compared with patients receiving IL-2/IFN-α (9.7 months). The median and mean number of doses of IL-2 were equivalent in both groups, as was toxicity. There were three treatment-related deaths, two in the IL-2- alone arm and one in the IL-2/IFN-α arm. The trial was terminated after the first interim analysis based on predefined early-stopping rules, which included termination if the response rate in the IL-2/IFN-α arm was less than 25%. Conclusion: Using the preparation, dose, and schedule of IL-2 in our trial, IFN-α failed to enhance significantly the response rate to high- dose IL-2 in the treatment of patients with advanced melanoma.
引用
收藏
页码:1969 / 1977
页数:9
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