*3-1-1 Higashi-ku, Maidashi, Fukuoka 812-8582, Japan.
Jpn J Clin Oncol. 2014 Feb;44(2):127-33. doi: 10.1093/jjco/hyt198. Epub 2013 Dec 29.
This study reports the findings of a Phase I/II, cohort, dose-escalation trial of amrubicin and irinotecan with the support of granulocyte colony-stimulation factor. This study aimed to determine the dose-limiting toxicity of the combination and to define the maximum-tolerated dose, as a recommended dose for Phase II trials. We also sought to obtain preliminary data on the efficacy of this combination as a frontline therapy for extensive-disease small-cell lung cancer.
We included 23 chemo-naïve patients with extensive-disease small-cell lung cancer in the trial. The amrubicin dose was escalated from 35 to 40 mg/m(2) (Levels 1 and 2, respectively) to determine the dose-limiting toxicity, with an unchanged dose of irinotecan at 50 mg/m(2).
Of nine patients, three experienced dose-limiting toxicities at Level 1 of prolonged Grade 4 neutropenia, Grade 3 febrile neutropenia and Grade 3 febrile neutropenia with Grade 3 diarrhea. At Level 2, two patients experienced dose-limiting toxicities of Grade 4 neutropenia and Grade 3 neutropenia with Grade 4 diarrhea. The maximum-tolerated doses and recommended doses for amrubicin and irinotecan were therefore determined to be 35 and 50 mg/m(2), respectively. The Level 1 trial was then expanded to 21 patients, 14 (70%) of whom showed partial responses to the recommended dose. The median progression-free and overall survival times were 6.37 and 15.21 months, respectively.
The combination of amrubicin and irinotecan with the support of granulocyte colony-stimulation factor produced a potent effect in chemo-naïve extensive-disease small-cell lung cancer patients. The use of biomarkers for this regimen may identify patients who are likely to suffer from treatment-ending severe adverse effects.
本研究报告了一项 I/II 期、队列、剂量递增试验的结果，该试验联合粒细胞集落刺激因子使用氨柔比星和伊立替康。本研究旨在确定该联合用药的剂量限制毒性，并确定最大耐受剂量，作为 II 期试验的推荐剂量。我们还试图获得该联合用药作为广泛期小细胞肺癌一线治疗的初步疗效数据。
我们将 23 例广泛期小细胞肺癌的初治患者纳入该试验。氨柔比星剂量从 35mg/m2（分别为 1 级和 2 级）升高至 40mg/m2，以确定剂量限制毒性，伊立替康剂量保持不变，为 50mg/m2。
在 9 例患者中，有 3 例患者发生剂量限制毒性，表现为 4 级中性粒细胞减少症持续时间延长、3 级发热性中性粒细胞减少症和 3 级发热性中性粒细胞减少症伴 3 级腹泻。在 2 级，有 2 例患者发生剂量限制毒性，表现为 4 级中性粒细胞减少症和 3 级中性粒细胞减少症伴 4 级腹泻。因此，氨柔比星和伊立替康的最大耐受剂量和推荐剂量分别确定为 35mg/m2 和 50mg/m2。随后，1 级试验扩大到 21 例患者，14 例（70%）患者对推荐剂量有部分反应。中位无进展生存期和总生存期分别为 6.37 个月和 15.21 个月。
粒细胞集落刺激因子支持下的氨柔比星和伊立替康联合用药对初治广泛期小细胞肺癌患者具有强大的疗效。该方案使用生物标志物可能有助于识别易发生治疗相关严重不良反应的患者。
