Hoffmann R, Müller I, Neuber K, Lassmann S, Buer J, Probst M, Oevermann K, Franzke A, Kirchner H, Ganser A, Atzpodien J
Department of Hematology and Oncology, Medizinische Hochschule Hannover, Germany.
Br J Cancer. 1998 Oct;78(8):1076-80. doi: 10.1038/bjc.1998.630.
Combined chemo-/immunotherapy has shown high objective response rates and a significant though small proportion of long-term complete responders in metastatic malignant melanoma. The purpose of this study was to determine response rates, freedom from treatment failure (FFTF) and overall survival in patients with advanced metastatic malignant melanoma treated with combined chemo-/immunotherapy, and to determine the value of a prognostic model for prediction of treatment outcome, FFTF and survival. Sixty-nine patients with metastatic malignant melanoma received combined chemo-/immunotherapy consisting of up to four cycles of DTIC (220 mg m(-2) i.v. days 1-3), cisplatin (35 mg m(-2) i.v. days 1-3), BCNU (150 mg m(-2) i.v. day 1, cycles 1 and 3 only) and tamoxifen (20 mg orally, daily). Two cycles of chemotherapy were followed by 6 weeks of outpatient immunotherapy with combined interleukin 2 (20 x 10(6) IU m(-2) days 3-5, weeks 1 and 4; 5 x 10(6) IU m(-2) days 1, 3, 5, weeks 2, 3, 5, 6) and interferon-alpha (6 x 10(6) IU m(-2) s.c. day 1, weeks 1 and 4; days 1, 3, 5, weeks 2, 3, 5, 6). All patients were evaluated on an intention-to-treat basis. Of 69 patients entered in the study, seven achieved complete remissions and 20 reached partial remissions with an objective response rate of 39% (95% confidence interval 28-52%). Median survival was 11 months, median FFTF was 5 months. Seven patients achieved ongoing long-term remissions, with maximum survival of 58 + months, and maximum FFTF of 58 + months. By Kaplan-Meier survival analysis and two-proportional Cox regression analysis, pretreatment performance status and serum lactic dehydrogenase were statistically significant and independent predictors of survival; risk groups could be defined as (a) the absence of both or (b) the presence of either one or both of these risk factors. Whereas survival and response were significantly influenced by patient risk, no influence could be demonstrated for FFTF. This combined outpatient chemo-/immunotherapy is feasible and results in objective response rates and survival similar to earlier trials. Pretreatment risk, as defined by serum lactate dehydrogenase (LDH) and performance status, has a significant impact on treatment outcome and patient survival.
化疗与免疫疗法联合应用已在转移性恶性黑色素瘤中显示出较高的客观缓解率，以及一小部分比例虽小但显著的长期完全缓解者。本研究的目的是确定接受化疗与免疫疗法联合治疗的晚期转移性恶性黑色素瘤患者的缓解率、无治疗失败生存期（FFTF）和总生存期，并确定一种预后模型对治疗结果、FFTF和生存期预测的价值。69例转移性恶性黑色素瘤患者接受了化疗与免疫疗法联合治疗，包括最多四个周期的达卡巴嗪（220mg/m²静脉注射，第1 - 3天）、顺铂（35mg/m²静脉注射，第1 - 3天）、卡莫司汀（仅第1周期和第3周期，150mg/m²静脉注射，第1天）和他莫昔芬（20mg口服，每日）。两个周期化疗后进行为期6周的门诊免疫治疗，联合使用白细胞介素2（20×10⁶IU/m²，第3 - 5天，第1周和第4周；5×10⁶IU/m²，第1、3、5天，第2、3、5、6周）和干扰素-α（6×10⁶IU/m²皮下注射，第1天，第1周和第4周；第1、3、5天，第2、3、5、6周）。所有患者均按意向性治疗原则进行评估。在纳入研究的69例患者中，7例实现完全缓解，20例达到部分缓解，客观缓解率为39%（95%置信区间28 - 52%）。中位生存期为11个月，中位FFTF为5个月。7例患者实现持续长期缓解，最长生存期为58 +个月，最长FFTF为58 +个月。通过Kaplan-Meier生存分析和双比例Cox回归分析，治疗前的体能状态和血清乳酸脱氢酶是生存的统计学显著且独立的预测因素；风险组可定义为（a）两者均不存在或（b）存在其中一个或两个这些风险因素。虽然生存和缓解受到患者风险的显著影响，但未发现对FFTF有影响。这种联合门诊化疗与免疫疗法是可行的，其客观缓解率和生存期与早期试验相似。由血清乳酸脱氢酶（LDH）和体能状态定义的治疗前风险对治疗结果和患者生存有显著影响。
