Kirkwood J M, Ibrahim J, Lawson D H, Atkins M B, Agarwala S S, Collins K, Mascari R, Morrissey D M, Chapman P B
University of Pittsburgh Medical Center, University of Pittsburgh Cancer Institute Melanoma Center, Department of Medicine, Division of Hematology-Oncology, Pittsburgh, PA, USA.
J Clin Oncol. 2001 Mar 1;19(5):1430-6. doi: 10.1200/JCO.2001.19.5.1430.
High-dose interferon alfa-2b (IFNalpha2b) is the only established adjuvant therapy of resectable high-risk melanoma. GM2-KLH/QS-21 (GMK) is a chemically defined vaccine that is one of the best developed of a range of vaccine candidates for melanoma. A single-institution phase III trial conducted at Memorial Hospital served as the impetus for an intergroup adjuvant E1694/S9512/C509801 trial, which recently completed enrollment of 880 patients. To build on the apparent benefit of IFNalpha2b in resectable high-risk American Joint Committee on Cancer (AJCC) stage IIB or III melanoma, this phase II study was designed to evaluate the combination of GMK and IFNalpha2b. The E2696 trial was undertaken to evaluate the toxicity and other effects of the established adjuvant high-dose IFNalpha2b regimen in relation to immune responses to GMK and to evaluate the potential clinical and immunologic effects of the combined therapies.
This trial enrolled 107 patients with resectable high- or very high-risk melanoma (AJCC stages IIB, III, and IV).
The results demonstrate that IFNalpha2b does not significantly inhibit immunoglobulin M or G serologic responses to the vaccine and that the combination of high-dose IFNalpha2b and GMK is well tolerated in this patient population.
Cox analysis of the results of the combination with IFNalpha2b show improvement in the relapse-free survival of patients with very high-risk melanoma (including those with resectable M1 disease).
高剂量干扰素α-2b（IFNα2b）是可切除的高危黑色素瘤唯一已确立的辅助治疗方法。GM2-KLH/QS-21（GMK）是一种化学定义明确的疫苗，是一系列黑色素瘤候选疫苗中研发得最好的之一。在纪念医院进行的一项单机构III期试验推动了一项组间辅助E1694/S9512/C509801试验，该试验最近完成了880例患者的入组。为了基于IFNα2b在可切除的高危美国癌症联合委员会（AJCC）IIB期或III期黑色素瘤中明显的益处，本II期研究旨在评估GMK与IFNα2b的联合应用。进行E2696试验是为了评估既定的辅助高剂量IFNα2b方案的毒性及其他效应与对GMK的免疫反应的关系，并评估联合治疗的潜在临床和免疫效应。
本试验纳入了107例患有可切除的高风险或极高风险黑色素瘤（AJCC IIB期、III期和IV期）的患者。
结果表明，IFNα2b不会显著抑制对该疫苗的免疫球蛋白M或G血清学反应，并且高剂量IFNα2b与GMK的联合应用在该患者群体中耐受性良好。
对与IFNα2b联合应用结果的Cox分析显示，极高风险黑色素瘤患者（包括那些有可切除M1疾病的患者）的无复发生存期有所改善。
