Bland K I, Kimura A K, Brenner D E, Basinger M A, Hirsch M, Hawkins I F, Pierson K K, Copeland E M
Department of Surgery, University of Florida College of Medicine, Gainesville 32610.
Ann Surg. 1989 Jan;209(1):73-80. doi: 10.1097/00000658-198901000-00011.
A phase II trial was conducted with 15 patients (mean age of 65.7 years) with locally recurrent or intransit melanoma of the extremities. After total outflow occlusion with pneumatic tourniquet, the cell-cycle nonspecific anti-neoplastic agent cis-diamminedicholoroplatinum (CDDP) was infused intra-arterially in a mean dose of 26.7 mg/m2 per infusion (2.6 infusions per patient). The aim of this study was to determine the efficacy of CDDP infusion for control of intransit and recurrent melanoma of the extremities. Three to four weeks postinfusion, all visible residual disease was resected. Partial remissions were observed in ten patients (67%); five patients achieved stable disease status. No patient had complete regression of disease. At an average follow-up interval of 18.3 months (range 4-44 months), the mean local/regional disease-free survival was 14.8 months. Eighty per cent of patients (twelve of 15) had local/regional control of disease at an average follow-up of 14.8 months after CDDP infusion and surgical resection. Of five melanoma-related deaths, three patients had had no local/regional recurrence at the time of their demise. Three compartment syndromes resulted as a complication of the infusional therapy and occurred within 1-3 days of the treatment. In vitro growth of melanoma from lymph nodes draining the infused area was seen in all subjects studied. Outgrowth from tumor within the tourniquet infusion area was observed in two patients, both of whom experienced recurrences clinically at 24-months' postinfusion. Pharmacokinetic data of total CDDP concentrations from tissue and blood (n = 4) were available from pretreatment to 1 hour post-therapy. Biopsy data from patients pre- and post-treatment suggest substantial tumor uptake of CDDP as compared to local or distal normal skin, with minimal CDDP loss to the systemic circulation. Pharmacologic and clinical data of this phase II trial suggest that intraarterial infusion with tourniquet outflow-occlusion augments tumor tissue levels of CDDP within the infused extremity and enhances local control of high-risk and intransit disease.
对15例（平均年龄65.7岁）四肢局部复发或转移的黑色素瘤患者进行了一项II期试验。在用气动止血带完全阻断血流后，细胞周期非特异性抗肿瘤药物顺二氯二氨铂（CDDP）通过动脉内输注，平均每次输注剂量为26.7mg/m²（每位患者输注2.6次）。本研究的目的是确定CDDP输注对控制四肢转移和复发性黑色素瘤的疗效。输注后3至4周，切除所有可见的残留病灶。10例患者（67%）观察到部分缓解；5例患者病情稳定。没有患者疾病完全消退。平均随访间隔为18.3个月（范围4 - 44个月），局部/区域无病生存期平均为14.8个月。80%的患者（15例中的12例）在CDDP输注和手术切除后平均随访14.8个月时实现了局部/区域疾病控制。在5例与黑色素瘤相关的死亡病例中，3例患者死亡时无局部/区域复发。作为输注治疗的并发症，出现了3例骨筋膜室综合征，均发生在治疗后1 - 3天内。在所有研究对象中均观察到输注区域引流淋巴结中黑色素瘤的体外生长。在2例患者中观察到止血带输注区域内肿瘤的生长，这2例患者在输注后24个月均出现临床复发。从预处理到治疗后1小时可获得组织和血液中总CDDP浓度的药代动力学数据（n = 4）。治疗前后患者的活检数据表明，与局部或远端正常皮肤相比，肿瘤对CDDP的摄取量很大，而进入体循环的CDDP损失最小。该II期试验的药理学和临床数据表明，采用止血带血流阻断的动脉内输注可提高输注肢体中CDDP的肿瘤组织水平，并增强对高危和转移疾病的局部控制。
