Sun W, Schuchter L M
University of Pennsylvania Cancer Center, Hematology-Oncology Division, 16 Penn Tower, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA.
Curr Treat Options Oncol. 2001 Jun;2(3):193-202. doi: 10.1007/s11864-001-0033-5.
The overall survival for patients with metastatic melanoma ranges from 4.7 to 11 months, with a median survival of 8.5 months. Standard treatment for patients with metastatic melanoma has not been defined. The range of treatment options includes close observation, surgical resection of isolated metastases, therapy with dacarbazine, combination chemotherapy, and participation in clinical trials. Numerous chemotherapeutic agents have shown activity in the treatment of malignant melanoma. Dacarbazine (DTIC-Dome; Bayer Corporation, West Haven, CT) has a response rate of 15% to 20% and remains the reference agent for the treatment of metastatic disease. Additional agents with single-agent activity include cisplatin, (Platinol-AQ; Bristol-Myers Oncology, Princeton, NJ); carmustine (BiCNU; Bristol-Myers Oncology, Princeton, NJ); paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ); and docetaxel (Taxotere; Rhone-Poulenc Rorer Pharmaceuticals, Collegeville, PA). Temozolomide (Temodar; Schering-Plough, Kenilworth, NJ), which is essentially an oral form of dacarbazine but with greater central nervous system penetrance, is associated with a response rate of 20%. Combination chemotherapy with or without tamoxifen has been extensively evaluated in patients with metastatic melanoma. Although the initial results with the Dartmouth regimen (dacarbazine, cisplatin, carmustine, and tamoxifen) were associated with overall response rates of 50% to 55% in single-institution studies, results from larger multicenter studies reveal responses rates ranging from 10% to 20%. Based on the results of several clinical trials, there is no evidence that the addition of tamoxifen improves the response rate. Another combination regimen is cisplatin, vinblastine, and dacarbazine (CVD), which is associated with a 20% to 25% response rate. There has been widespread interest in developing immunotherapies against metastatic melanoma. Interferon (IFN)-alfa and interleukin (IL)-2 as single agents have produced response rates in the 15% to 20% range. Biochemotherapy, which is a combination of immunotherapy and cytotoxic chemotherapy, has been studied in patients with metastatic melanoma. Multiple phase II studies have demonstrated high response rates but unclear impact on overall survival. Therapy is associated with significant toxicity. Ongoing randomized clinical trials will clarify the role of biochemotherapy in patients with metastatic melanoma. Ongoing new approaches to treatment include the therapeutic use of vaccines alone or in combination with cytokines.
转移性黑色素瘤患者的总生存期为4.7至11个月，中位生存期为8.5个月。转移性黑色素瘤患者的标准治疗方法尚未确定。治疗选择范围包括密切观察、孤立转移灶的手术切除、达卡巴嗪治疗、联合化疗以及参与临床试验。许多化疗药物已显示出对恶性黑色素瘤的治疗活性。达卡巴嗪（DTIC-Dome；拜耳公司，康涅狄格州韦斯特黑文）的缓解率为15%至20%，仍然是转移性疾病治疗的参考药物。具有单药活性的其他药物包括顺铂（Platinol-AQ；百时美施贵宝肿瘤学公司，新泽西州普林斯顿）；卡莫司汀（BiCNU；百时美施贵宝肿瘤学公司，新泽西州普林斯顿）；紫杉醇（Taxol；百时美施贵宝公司，新泽西州普林斯顿）；以及多西他赛（Taxotere；罗纳普朗克罗瑞尔制药公司，宾夕法尼亚州学院村）。替莫唑胺（Temodar；先灵葆雅公司，新泽西州肯尼沃思）本质上是达卡巴嗪的口服剂型，但具有更高的中枢神经系统渗透性，缓解率为20%。在转移性黑色素瘤患者中，对含或不含他莫昔芬的联合化疗进行了广泛评估。尽管在单机构研究中，达特茅斯方案（达卡巴嗪、顺铂、卡莫司汀和他莫昔芬）的初步结果显示总缓解率为50%至55%，但更大规模多中心研究的结果显示缓解率在10%至20%之间。基于多项临床试验的结果，没有证据表明添加他莫昔芬能提高缓解率。另一种联合方案是顺铂、长春碱和达卡巴嗪（CVD），其缓解率为20%至25%。开发针对转移性黑色素瘤的免疫疗法引起了广泛关注。干扰素（IFN）-α和白细胞介素（IL）-2作为单药使用时的缓解率在15%至20%之间。生物化疗是免疫疗法和细胞毒性化疗的联合应用，已在转移性黑色素瘤患者中进行了研究。多项II期研究显示缓解率较高，但对总生存期的影响尚不清楚。该疗法伴有显著毒性。正在进行的随机临床试验将阐明生物化疗在转移性黑色素瘤患者中的作用。正在进行的新治疗方法包括单独或与细胞因子联合使用疫苗进行治疗。
