Paciucci P A, Holland J F, Glidewell O, Odchimar R
Department of Neoplastic Diseases, Mount Sinai Cancer Center, Mount Sinai School of Medicine, New York, NY 10029.
J Clin Oncol. 1989 Jul;7(7):869-78. doi: 10.1200/JCO.1989.7.7.869.
Twenty-five patients with disseminated cancer (nine with renal cell carcinoma, five with melanoma, three with Hodgkin's lymphoma and chronic myelocytic leukemia [CML], two with soft tissue sarcoma, one each with large-cell lymphoma, breast cancer, and colon cancer), 13 males and 12 females, aged 25 to 68, were treated with recombinant human interleukin-2 (rIL2) by continuous infusion and adoptive transfer of autologous lymphocytes activated in vitro with IL2. Patients underwent leukapheresis on days 1, 8, 15, and 22 of the treatment. Cells, bulk activated for 20 hours in serum-free culture medium with 1,000 U IL2/mL in transfusion transfer packs as culture vessels, were transfused the following day. The infusion of IL2 by continuous infusion for six days started immediately after each adoptive transfer for 4 weekly courses. The dose of IL2 was escalated weekly in each patient; starting doses of IL2 were also escalated in subsequent cohorts of patients until maximally tolerated doses were reached. Nine patients had objective tumor regressions (three with renal cell cancer, two with Hodgkin's lymphoma, and one each with melanoma, sarcoma, breast, and colon cancer). Six responses were partial, two were minor, and one was mixed. Responding patients were maintained with IL2 by continuous infusion for six days every 6 to 8 weeks, without adoptive cell transfer. The median duration of responses was 16 weeks (3 to 60 + weeks). Tumor regression was related to the dose of IL2 (greater than or equal to 3.4 x 10(6) U/m2/d for six days) and to the in vivo lymphoproliferative effects of the lymphokine, but not to the total number of cells adoptively transferred. Side effects of treatment were transient and quickly reversible. Renal, hepatic dysfunction, and dyspnea were directly related to the dose of IL2 and to lymphocytosis. Other toxicities were mild hypotension with mild fluid retention, oral mucositis, anemia, thrombocytopenia, fever, and fatigue.
25例播散性癌症患者（9例肾细胞癌、5例黑色素瘤、3例霍奇金淋巴瘤和慢性粒细胞白血病[CML]、2例软组织肉瘤、1例大细胞淋巴瘤、1例乳腺癌和1例结肠癌），男性13例，女性12例，年龄25至68岁，接受了重组人白细胞介素-2（rIL2）持续输注及经IL2体外激活的自体淋巴细胞过继性转移治疗。患者在治疗的第1、8、15和22天进行白细胞分离术。细胞在作为培养容器的输血转移袋中，于含1000 U IL2/mL的无血清培养基中批量激活20小时，次日进行输注。每次过继性转移后立即开始为期6天的rIL2持续输注，共进行4个每周疗程。每位患者的IL2剂量每周递增；后续患者队列的IL2起始剂量也逐步增加，直至达到最大耐受剂量。9例患者出现客观肿瘤消退（3例肾细胞癌、2例霍奇金淋巴瘤、1例黑色素瘤、1例肉瘤、1例乳腺癌和1例结肠癌）。6例为部分缓解，2例为轻度缓解，1例为混合性缓解。缓解患者每6至8周接受为期6天的rIL2持续输注维持治疗，不再进行过继性细胞转移。缓解的中位持续时间为16周（3至60 +周）。肿瘤消退与IL2剂量（连续6天大于或等于3.4×10(6) U/m2/d）及淋巴因子的体内淋巴细胞增殖效应有关，但与过继性转移的细胞总数无关。治疗的副作用是短暂的且可迅速逆转。肾功能、肝功能障碍及呼吸困难与IL2剂量及淋巴细胞增多直接相关。其他毒性反应为轻度低血压伴轻度液体潴留、口腔黏膜炎、贫血、血小板减少、发热和疲劳。
