Fukuda Minoru, Soda Hiroshi, Soejima Yoshifumi, Fukuda Masaaki, Kinoshita Akitoshi, Takatani Hiroshi, Kasai Takashi, Nagashima Seiji, Kawabata Shigeru, Doi Seiji, Kohno Shigeru, Oka Mikio
Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, and National Ureshino Hospital, Saga, Japan.
Cancer Chemother Pharmacol. 2006 Nov;58(5):601-6. doi: 10.1007/s00280-006-0188-7. Epub 2006 Feb 4.
The combination of carboplatin and etoposide is currently considered the most appropriate regimen for treating elderly patients with small-cell lung cancer (SCLC). Previous reports on elderly patients, 70 years or older, found that the recommended dose was close to that of younger patients. Then, we conducted a phase I study of carboplatin and etoposide in elderly patients, 75 years or older, with SCLC. This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT).
Twenty-six patients fulfilling the eligibility criteria, chemotherapy-naive, performance status (PS) of 0-2, age>or=75, and adequate organ functions were enrolled. Patients' characteristics were: male/female=21/5; PS 0/1/2=9/11/6; median age (range)=78 (75-82); and limited/extensive stage=16/10. The patients intravenously received carboplatin with a target AUC of 4 or 5 mg min/ml (Chatelut formula) on day 1 and etoposide at 80-120 mg/m2 on days 1, 2 and 3. Therapy was repeated four times in every 4 weeks.
The MTD of carboplatin/etoposide was AUC=5/80, 4/110, and 4/120. The DLTs were thrombocytopenia, neutropenia, leukopenia, and febrile neutropenia. Overall, grade 4 thrombocytopenia, neutropenia (>or=4 days), leukopenia (>or=4 days), and febrile neutropenia occurred in 27, 20, 7, and 13% of cases at MTD levels, respectively, and 0% at other levels. Twenty of 26 patients showed objective responses (2CR, 18PR; RR=77%).
A dose of carboplatin of AUC=4 and etoposide of 100 mg/m2 was recommended in this regimen.
目前认为卡铂和依托泊苷联合用药是治疗老年小细胞肺癌（SCLC）患者的最合适方案。先前针对70岁及以上老年患者的报告发现，推荐剂量与年轻患者相近。随后，我们对75岁及以上老年SCLC患者进行了卡铂和依托泊苷的I期研究。本研究旨在确定最大耐受剂量（MTD）和剂量限制性毒性（DLT）。
纳入26例符合入选标准的患者，这些患者未曾接受过化疗，体能状态（PS）为0 - 2，年龄≥75岁，且器官功能良好。患者特征为：男/女 = 21/5；PS 0/1/2 = 9/11/6；中位年龄（范围）= 78（75 - 82）岁；局限期/广泛期 = 16/10。患者于第1天静脉给予目标AUC为4或5 mg·min/ml（Chatelut公式）的卡铂，第1、2和3天给予80 - 120 mg/m²的依托泊苷。每4周重复治疗4次。
卡铂/依托泊苷的MTD为AUC = 5/80、4/110和4/120。DLT为血小板减少、中性粒细胞减少、白细胞减少和发热性中性粒细胞减少。总体而言，在MTD水平时，4级血小板减少、中性粒细胞减少（≥4天）、白细胞减少（≥4天）和发热性中性粒细胞减少分别发生在27%、20%、7%和13%的病例中，在其他水平时为0%。26例患者中有20例出现客观缓解（2例完全缓解，18例部分缓解；缓解率 = 77%）。
该方案推荐卡铂剂量为AUC = 4，依托泊苷剂量为100 mg/m²。
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