Eskander E D, Harvey H A, Givant E, Lipton A
Department of Medicine, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey, USA.
Am J Clin Oncol. 1997 Oct;20(5):511-4. doi: 10.1097/00000421-199710000-00016.
We evaluated the effects of the addition of escalating doses of tumor necrosis factor (TNF) to two fixed doses and schedules of a combination of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) to determine the maximum tolerated dose of this three-cytokine combination and its feasibility as an outpatient regimen. Eighteen patients with metastatic cancer were enrolled. Each course consisted of 3 consecutive weeks of treatment with IFN-alpha 9 x 10(6) IU/m2/day intramuscularly (i.m.) or subcutaneously (s.c.) days 1, 3, and 5 each week for 3 weeks plus IL-2 continuous infusion 1 x 10(6) IU/m2/day (group A) or 3 x 10(6) IU/m2/day (group B) days 1-5 each week for 3 weeks. TNF was administered only during the first week of each course intravenously (i.v.) for 2 h on days 1-5. The dose of TNF was escalated (40, 80, 120 micrograms/m2) in cohorts of 3 patients. The most common side effects were fever, chills, and fatigue in all patients. Grade 3-4 toxicity included anemia (3 patients), thrombocytopenia (1 patients), arrhythmia (2 patients), pulmonary edema (3 patients),- and weight loss (1 patient). Five patients withdrew from study due to toxicity. The combination of the three cytokines is feasible as an outpatient regimen in one of the following combinations: (a) TNF 80 micrograms/m2/day as 2-h infusion on days 1-5 + IL-2 1 x 10(6) IU/m2/day continuous infusion on days 1-5 for 3 weeks + IFN-alpha 9 x 10(6) IU/m2/day s.c. or i.m. on days 1, 3, and 5 for 3 weeks, or (b) TNF 40 micrograms/m2/day as a 2-h infusion on days 1-5 + IL-2 3 x 10(6) IU/m2/day continuous infusion on days 1-5 for 3 weeks + IFN-alpha 9 x 10(6) IU/m2/day s.c. or i.m. on days 1, 3, and 5 for 3 weeks.
我们评估了在两种固定剂量和给药方案的白细胞介素-2（IL-2）与干扰素-α（IFN-α）联合用药基础上加用递增剂量肿瘤坏死因子（TNF）的效果，以确定这种三细胞因子联合用药的最大耐受剂量及其作为门诊治疗方案的可行性。招募了18例转移性癌症患者。每个疗程包括连续3周的治疗，第1、3、5天，每周3天，肌内注射（i.m.）或皮下注射（s.c.）干扰素-α 9×10⁶IU/m²/天，共3周，加上第1 - 5天，每周5天，IL-2持续输注1×10⁶IU/m²/天（A组）或3×10⁶IU/m²/天（B组），共3周。TNF仅在每个疗程的第一周第1 - 5天静脉注射（i.v.）2小时。TNF剂量在每组3例患者中递增（40、80、120微克/m²）。所有患者中最常见的副作用是发热、寒战和疲劳。3 - 4级毒性包括贫血（3例患者）、血小板减少（1例患者）、心律失常（2例患者）、肺水肿（3例患者）和体重减轻（1例患者）。5例患者因毒性退出研究。三细胞因子联合用药作为门诊治疗方案在以下一种组合中是可行的：（a）第1 - 5天，TNF 80微克/m²/天，2小时输注 + 第1 - 5天，IL-2 1×10⁶IU/m²/天，持续输注3周 + 第1、3、5天，干扰素-α 9×10⁶IU/m²/天，皮下或肌内注射，共3周；或（b）第1 - 5天，TNF 40微克/m²/天，2小时输注 + 第1 - 5天，IL-2 3×10⁶IU/m²/天，持续输注3周 + 第1、3、5天，干扰素-α 9×10⁶IU/m²/天，皮下或肌内注射，共3周。
