Pollera C F, Calabresi F, Moreschi M, Ruggeri E M, Giannarelli D, Masciulli R, Testa U, Peschle C
Division of Medical Oncology I, Istituto Regina Elena per lo Studio e la Cura dei Tumori, Rome, Italy.
Cancer Invest. 1994;12(6):574-87. doi: 10.3109/07357909409023042.
Given the antitumor activity of interleukin-2 (IL-2) against some drug-resistant cancer cells, 17 previously untreated patients with small cell lung cancer entered a pilot study to evaluate the feasibility, efficacy, and immunological effects of combining 12-week high dose-intense chemotherapy based on a modified Evans regimen (CAV/PE) with different IL-2 schedules (6-12 MU/m2 week as a 48-72-h infusion using the same cumulative dose, 72 MU/m2). Despite significant myelotoxicity, up to 70% of the intended dose intensity was delivered, showing no differences with regard to the IL-2 schedule used. Immunotherapy-induced toxicity was usually mild and manageable. No limiting effects were observed in patients receiving immunotherapy except for a very poor compliance to the 12-week IL-2 regimen. The low-dose 72-h infusion was the optimal IL-2 schedule. As given in this study, neither of the alternating CAV/PE regimens abrogated the effects of IL-2 on T-cell and NK-cell subsets, showing typical kinetics with rebound in lymphocytes following each discontinuation of the IL-2. While immunological changes cannot predict the antitumor effect of IL-2, they are consistent with those described for IL-2 alone, suggesting its compatibility with high dose-intense chemotherapy. Although no definite advantages have been demonstrated in this small pilot study with significant unbalanced prognostic factors (12% 2-year survival), both the preserved immunostimulatory effects and the lack of limiting overlapping toxicity make this combined approach promising and worthy of further clinical investigation.
鉴于白细胞介素-2（IL-2）对某些耐药癌细胞具有抗肿瘤活性，17例既往未接受过治疗的小细胞肺癌患者进入一项试点研究，以评估基于改良埃文斯方案（CAV/PE）的12周高剂量强化化疗与不同IL-2给药方案（6-12 MU/m²每周，以48-72小时输注方式使用相同累积剂量，即72 MU/m²）联合应用的可行性、疗效及免疫效应。尽管存在显著的骨髓毒性，但仍达到了预期剂量强度的70%，且不同IL-2给药方案之间未显示出差异。免疫治疗引起的毒性通常较轻且易于控制。除了对12周IL-2方案的依从性非常差外，在接受免疫治疗的患者中未观察到限制效应。低剂量72小时输注是最佳的IL-2给药方案。如本研究所示，交替的CAV/PE方案均未消除IL-2对T细胞和NK细胞亚群的影响，每次停用IL-2后淋巴细胞均出现典型的反弹动力学。虽然免疫变化无法预测IL-2的抗肿瘤效果，但与单独使用IL-2时所描述的情况一致，表明其与高剂量强化化疗具有相容性。尽管在这项具有显著预后因素不平衡（2年生存率为12%）的小型试点研究中未证明明确的优势，但保留的免疫刺激作用以及缺乏限制重叠毒性使得这种联合方法具有前景且值得进一步临床研究。
