ADJUVANT ALFA-2B FOR MELANOMA PATIENTS WITH EARLY LYMPH NODE METASTASIS

ALFA-2B 辅助治疗早期淋巴结转移黑色素瘤患者

• 批准号: 7378560
• 负责人: DAVID N KRAG
• 金额: $ 0.11万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-09 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378560
• 关键词: interferon alpha; lymph nodes; melanoma; metastasis; neoplasm /cancer; prognosis

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Results of ECOG Trial EST 1684 demonstrated that adjuvant therapy with recombinant interferon alfa-2b improves both disease-free and overall survival for melanoma patients with a high risk of recurrence. However, the majority of patients in this trial had advanced nodal metastasis; i.e., palpable lymph nodes. Using the technique of lymphatic mapping and sentinel lymph node biopsy, it is now possible to identify very early microscopic nodal metastasis. Using polymerase chain reaction (PCR) technology, it is also possible to detect "submicroscopic" nodal metastasis. Patients with a single positive lymph node have a much better prognosis than patients with multiple positive nodes, with a 10 year overall survival rate of 40% or better. Although we do not yet know the long-term prognosis of patients with submicroscopic nodal metastasis, it is assumed that it will be better than those with microscopic disease. This patient population is significantly different than those studied in ECOG Trial EST 1684. A significant proportion of these patients can be expected to be cured of their disease by lymphadenectomy alone. Because the toxicity of adjuvant interferon alfa-2b can be significant, it is important to determine whether these subsets of patients benefit from therapy. The central hypothesis of the Sunbelt Melanoma Trial is that regional lymphadenectomy plus adjuvant high dose interferon alfa-2b therapy improves diseasefree and overall survival for melanoma patients with early (sentinel lymph node-only) nodal metastasis compared to lymphadenectomy alone. The protocol is divided into two parts, designated Protocols A and B. Primary endpoints are disease-free and overall survival. Protocol A is for patients with positive sentinel node(s) detected by histology or immunohistochemistry. Patients with more than one positive sentinel lymph node, any positive non-sentinel lymph node, or any node with extracapsular extension of tumor will receive standard interferon alfa-2b therapy. Three-hundred patients with a single positive sentinel lymph node will be stratified by tumor thickness and randomized to receive lymphadenectomy alone or lymphadenectomy plus interferon alfa-2b therapy. Protocol B is for patients with a sentinel node that is positive only by PCR analysis for tyrosinase MRNA. If the sentinel node is negative for tyrosinase MRNA by PCR analysis, the patients will be followed with no further treatment. If the PCR test is positive for the presence of tyrosinase MRNA, 450 patients will be stratified by tumor thickness and randomized to one of three treatment arms: observation, lymphadenectomy alone, or lymphadenectomy plus interferon alfa-2b therapy. Furthermore, all patients will undergo prospective analysis of peripheral blood by PCR to detect circulating melanoma cells in order to determine the predictive value of this molecular staging test.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。ECOG试验EST 1684的结果表明，重组干扰素α-2b辅助治疗可改善复发风险高的黑色素瘤患者的无病生存期和总生存期。然而，本试验中的大多数患者具有晚期淋巴结转移;即，可触及淋巴结利用淋巴映射和前哨淋巴结活检技术，现在可以识别非常早期的显微镜下淋巴结转移。使用聚合酶链反应（PCR）技术，也可以检测“亚显微”淋巴结转移。单个淋巴结阳性的患者比多个淋巴结阳性的患者预后好得多，10年总生存率为40%或更高。虽然我们还不知道亚显微镜下淋巴结转移患者的长期预后，但可以假设它会比显微镜下疾病患者好。该患者人群与ECOG试验EST 1684中研究的患者人群显著不同。这些患者中有很大一部分可以通过淋巴结切除术治愈。因为辅助干扰素α-2b的毒性可能是显著的，所以确定这些患者子集是否从治疗中获益是重要的。Sunbelt黑色素瘤试验的中心假设是，与单纯淋巴结切除术相比，区域淋巴结切除术加辅助高剂量干扰素α-2b治疗可改善早期（仅前哨淋巴结）淋巴结转移的黑色素瘤患者的无病生存率和总生存率。该协议分为两部分，称为协议A和B。主要终点是无病生存期和总生存期。方案A适用于通过组织学或免疫组织化学检测到前哨淋巴结阳性的患者。具有多于一个阳性前哨淋巴结、任何阳性非前哨淋巴结或任何具有肿瘤囊外延伸的淋巴结的患者将接受标准干扰素α-2b治疗。300例单个前哨淋巴结阳性的患者将按肿瘤厚度分层，随机接受单纯淋巴结切除术或淋巴结切除术加干扰素α-2b治疗。方案B适用于前哨淋巴结仅通过酪氨酸酶mRNA PCR分析呈阳性的患者。如果前哨淋巴结通过PCR分析为酪氨酸酶mRNA阴性，则患者将不接受进一步治疗。如果PCR检测结果为酪氨酸酶mRNA阳性，则将450例患者按肿瘤厚度分层，并随机分配至三个治疗组之一：观察组、单纯淋巴结切除术组或淋巴结切除术加干扰素α-2b治疗组。此外，所有患者将通过PCR进行外周血前瞻性分析，以检测循环黑色素瘤细胞，以确定该分子分期试验的预测价值。