Rossi C R, Lejeune F J, Pontes L, Foletto M, De Salvo G L, Pilati P L, Mocellin S, Ribeiro M, Lopes M, Lise M
Clinica Chirurgica II, University of Padova, Padova, Italy.
Melanoma Res. 2003 Jun;13(3):293-7. doi: 10.1097/00008390-200306000-00011.
Isolation limb perfusion (ILP) is the treatment of choice for locally advanced limb melanoma. With melphalan, the referral drug, complete response (CR) is achieved in about 50% of patients, but significant local toxicity occurs in up to 30%. The aim of the present phase I-II study was to challenge fotemustine (F) in ILP after systemic chemosensitization with dacarbazine (DTIC), given its lower toxicity and greater efficacy, as reported in a previous pilot study. Eleven patients with locally advanced limb melanoma were subdivided into triplets, and given F ILP at escalating doses (starting from 25 mg/l) after intravenous administration of 500 mg/m2 DTIC. Acute and chronic locoregional and systemic toxicity, tumour response and clinical outcome were evaluated. Two patients in the first triplet had G3-G4 local toxicity, so that the scheduled F dosage was halved. At drug levels of 12.5, 15.6 and 18.2 mg/l, local toxicity decreased, but only one of eight patients showed CR. The trial was then interrupted due to the low tolerability and poor efficacy of this perfusion regimen. At present, F ILP after DTIC chemosensitization should not be recommended for the treatment of locally advanced limb melanoma.
隔离肢体灌注（ILP）是局部晚期肢体黑色素瘤的首选治疗方法。使用推荐药物美法仑时，约50%的患者可实现完全缓解（CR），但高达30%的患者会出现严重的局部毒性。鉴于在前一项初步研究中报告的较低毒性和更高疗效，本I-II期研究的目的是在用达卡巴嗪（DTIC）进行全身化疗增敏后，在ILP中应用福莫司汀（F）。11例局部晚期肢体黑色素瘤患者被分成三组，在静脉注射500mg/m² DTIC后，以递增剂量（从25mg/l开始）给予F ILP。评估急性和慢性局部及全身毒性、肿瘤反应和临床结果。第一组中的两名患者出现3-4级局部毒性，因此将预定的F剂量减半。在药物水平为12.5、15.6和18.2mg/l时，局部毒性降低，但八名患者中只有一名显示CR。由于该灌注方案耐受性低且疗效差，试验随后中断。目前，不建议在DTIC化疗增敏后使用F ILP治疗局部晚期肢体黑色素瘤。
