Rinehart J J, Triozzi P L, Lee M H, Aldrich W, Young D
Division of Hematology and Oncology, Texas A&M University College of Medicine, Temple 76508.
Mol Biother. 1992 Jun;4(2):77-82.
To determine if intensive chemotherapy consisting of cyclophosphamide (C), etoposide (E), and cisplatin (P) (CEP) may be usefully combined with recombinant human interleukin-2 (rhIL-2), we examined a murine tumor model designed to approximate a common clinical situation: macroscopic, drug-resistant cancer. Using C57BL/6 mice with extensive tumor burden 10 days after intravenous B16 melanoma cell injection, we observed (1) C, E, and P synergize to enhance survival but do not cure mice at the highest tolerable dose (C = 200 mg/kg, E = 60 mg/kg, and P = 3 mg/kg); (2) rhIL-2 at 3 x 10(5) U (subcutaneously) daily for 4 days administered 10-18 days after B16 injection significantly improves survival; (3) CEP plus rhIL-2 is more effective than CEP alone only when rhIL-2 is administered before CEP; (4) CEP suppresses IL-2-induced lymphokine-activated killer cell activity in the spleen; and (5) rhIL-2 protects mice incompletely from the immunologic and hematologic suppression of CEP. Our results suggest that intensive chemotherapy combined with rhIL-2 may be beneficial. The success of any such combination may be schedule dependent.
为了确定由环磷酰胺（C）、依托泊苷（E）和顺铂（P）组成的强化化疗方案（CEP）是否能与重组人白细胞介素-2（rhIL-2）有效联合，我们研究了一种旨在模拟常见临床情况的小鼠肿瘤模型：肉眼可见的耐药性癌症。在静脉注射B16黑色素瘤细胞10天后，使用肿瘤负荷较大的C57BL/6小鼠，我们观察到：（1）C、E和P协同作用可提高生存率，但在最高耐受剂量（C = 200 mg/kg，E = 60 mg/kg，P = 3 mg/kg）下不能治愈小鼠；（2）在B16注射后10 - 18天，每天皮下注射3×10⁵ U rhIL-2，共4天，可显著提高生存率；（3）仅当rhIL-2在CEP之前给药时，CEP加rhIL-2才比单独使用CEP更有效；（4）CEP抑制脾脏中IL-2诱导的淋巴因子激活的杀伤细胞活性；（5）rhIL-2不能完全保护小鼠免受CEP的免疫和血液学抑制。我们的结果表明，强化化疗联合rhIL-2可能有益。任何此类联合方案的成功可能取决于给药方案。
