Di Filippo F, Garinei R, Anzà M, Cavaliere F, Giannarelli D, Cagol P P, Rossi C R, Santinami M, Deraco M, Botti C, Perri P, Di Filippo S, Piarulli L, Bruno P
Department of Surgery, Regina Elena National Cancer Institute, Rome Italy.
J Exp Clin Cancer Res. 2003 Dec;22(4 Suppl):81-7.
Hyperthermic antiblastic perfusion/HAP) has been proven to be an effective neoadjuvant treatment in the treatment of advanced soft tissue limb sarcoma. As a matter of fact high percentage of limb sparing surgery, local control and functional results have been obtained wide this technique. Many antineoplastic drugs have been associated to hyperthermia by isolation limb perfusion, the aim of this paper was to describe the results obtained with doxorubicin in association to hyperthermia with or without Tumor Necrosis Factor (TNF) alpha in order to identify the most effective regimen in the multidisciplinary treatment of soft tissue limb sarcoma. A total of 106 patients have been evaluated. Three different study were performed: the first was a phase I study carried out in order to assess the maximum tolerable dose (MTD) of doxorubicin during HAP; the second was a phase II study with doxorubicin, and the third was a phase I - II study aimed at evaluating the MTD and tumor response of TNF alpha in association to doxorubicin and hyperthermia. Grade IV limb toxicity was recorded in 11 patients ( 4 in trial A, 3 in trial B, and 4 in trial C). The grade of limb reaction was strictly related to TNF dosage (> 1 mg) and temperature level (> 41.5 degrees C), therefore the best regimen is represented by temperature level not exceeding 41.5 degrees C and 1 mg of TNFalpha. The trimodality association (TNF, doxorubicin and hyperthermia) was proven to be the best regimen able to obtain a 77% of objective response (complete response, 22%) and a 77% of limb sparing in patients candidate to amputation. The results above mentioned showed the HAP with doxorubicin and TNFalpha (1 mg) is a very effective neoadjuvant treatment in the multidisciplinary treatment of advanced soft tissue limb sarcoma.
热灌注化疗（HAP）已被证明是治疗晚期肢体软组织肉瘤的一种有效新辅助治疗方法。事实上，采用该技术已获得了高比例的保肢手术、局部控制和功能结果。通过隔离肢体灌注，许多抗肿瘤药物已与热疗联合应用。本文旨在描述阿霉素联合热疗（无论有无肿瘤坏死因子（TNF）α）所取得的结果，以便确定在肢体软组织肉瘤多学科治疗中最有效的方案。共评估了106例患者。进行了三项不同的研究：第一项是I期研究，旨在评估热灌注化疗期间阿霉素的最大耐受剂量（MTD）；第二项是阿霉素的II期研究；第三项是I-II期研究，旨在评估TNFα联合阿霉素和热疗的MTD及肿瘤反应。11例患者记录到IV级肢体毒性（试验A中4例，试验B中3例，试验C中4例）。肢体反应程度与TNF剂量（>1mg）和温度水平（>41.5℃）密切相关，因此最佳方案为温度水平不超过41.5℃且TNFα为1mg。三联疗法（TNF、阿霉素和热疗）被证明是最佳方案，能够使有截肢指征的患者获得77%的客观缓解率（完全缓解率为22%）和77%的保肢率。上述结果表明，阿霉素联合TNFα（1mg）的热灌注化疗在晚期肢体软组织肉瘤多学科治疗中是一种非常有效的新辅助治疗方法。
