Cascinelli N, Belli F, Marchini S, Marolda R, Prada A, Sciorelli G, Villani F, Gambacorti-Passerini C, Galazka A, Parmiani G
Division of Surgical Oncology B, Istituto Nazionale Tumori, Milano, Italy.
Tumori. 1989 Jun 30;75(3):233-44. doi: 10.1177/030089168907500309.
From January 1987 to February 1988, 15 stage IV melanoma patients were treated with two courses of bolus injection of rIL-2 plus LAK cell infusions at the National Cancer Institute of Milan. The original treatment regimen included a first course of rIL-2 administration (400 micrograms/m2 bolus injection 3 times a day [TID] for 4 days) and a second course of rIL-2 administration (800 micrograms/m2 bolus injection TID for 7 days) separated by 4 consecutive daily leukaphereses. Autologous lymphokine activated killer (LAK) cells were reinfused into each patient on three occasions during the second period of rIL-2 administration. Due to the appearance of grade III-IV neurological, hepatic and cardiopulmonary toxicity, 7 patients discontinued dosing before the end of treatment, one patient desired to be withdrawn and one patient died from rapidly progressive disease, although complications of rIL-2 administration may have contributed to her death. Only 6 patients completed the schedule without evidence of major intolerance, even though the planned dose during the second course of rIL-2 was reduced to 400 micrograms/m2. The complete duration of treatment ranged from 11 to 19 days. The total dose of rIL-2 injected ranged from 12.6 to 30.4 mg. The number of infused LAK cells ranged from 15.5 x 10(9) to 60 x 10(9)/patient. Two of the 14 evaluable patients showed a minor anti-tumor response. In 5 patients new metastases in other sites were documented from 2 to 5 months after completion of dosing. No apparent association was found between progression of the disease (or the appearance of new metastases) and the total dose of rIL-2 injected, the number of LAK cells administered or the number of days of treatment. By December 1988, all patients had died of their disease in a period ranging from 3 to 14 months from the last injection of rIL-2. The lack of significant clinical responses in this study and the high toxicity of this treatment lead us to conclude that at least as far as melanoma patients are concerned, adoptive immunotherapy with rIL-2 plus LAK cells (as described here) is not a justifiable treatment option unless new evidence presents itself.
1987年1月至1988年2月，米兰国家癌症研究所对15例IV期黑色素瘤患者进行了两个疗程的大剂量注射重组白细胞介素-2（rIL-2）加淋巴因子激活的杀伤细胞（LAK细胞）输注治疗。最初的治疗方案包括第一个疗程的rIL-2给药（400微克/平方米，每日3次大剂量注射，共4天）和第二个疗程的rIL-2给药（800微克/平方米，每日3次大剂量注射，共7天），中间间隔连续4天的白细胞分离术。在第二个rIL-2给药期内，自体淋巴因子激活的杀伤（LAK）细胞分三次回输到每位患者体内。由于出现III-IV级神经、肝脏和心肺毒性，7例患者在治疗结束前停止给药，1例患者要求退出，1例患者死于疾病快速进展，尽管rIL-2给药的并发症可能促成了她的死亡。只有6例患者完成了治疗方案，且无明显不耐受迹象，尽管第二个rIL-2疗程的计划剂量降至400微克/平方米。治疗的总时长为11至19天。注射的rIL-2总剂量为12.6至30.4毫克。输注的LAK细胞数量为每位患者15.5×10⁹至60×10⁹。14例可评估患者中有2例显示出轻微的抗肿瘤反应。5例患者在完成给药后2至5个月记录到其他部位出现新的转移灶。未发现疾病进展（或新转移灶的出现）与注射的rIL-2总剂量、给予的LAK细胞数量或治疗天数之间存在明显关联。到1988年12月，所有患者在最后一次注射rIL-2后的3至14个月内均死于疾病。本研究中缺乏显著的临床反应以及该治疗的高毒性使我们得出结论，至少就黑色素瘤患者而言，除非有新的证据出现，否则用rIL-2加LAK细胞进行过继性免疫治疗（如此处所述）并非合理的治疗选择。
