Ando M, Eguchi K, Shinkai T, Tamura T, Ohe Y, Yamamoto N, Kurata T, Kasai T, Ohmatsu H, Kubota K, Sekine I, Hojo N, Matsumoto T, Kodama T, Kakinuma R, Nishiwaki Y, Saijo N
The Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Br J Cancer. 1997;76(11):1494-9. doi: 10.1038/bjc.1997.584.
We conducted a phase I study of irinotecan (CPT-11) and etoposide (VP-16) given sequentially to untreated patients with metastatic non-small-cell lung cancer. Arm A: CPT-11 was given over 90 min on days 1-3 and VP-16 was given over 60 min on days 4-6. Arm B: VP-16 was given on days 1-3 and CPT-11 on days 4-6. G-CSF was given to all patients daily on days 7-17. Twenty-seven patients were entered randomly at the two arms. The major dose-limiting toxicities in arms A and B were granulocytopenia and diarrhoea. Transient elevations of transaminases and bilirubin were observed in both arms. The degree of the toxicities did not differ between the two arms. The maximum tolerated doses (MTDs) were 60 mg m-2 CPT-11 and 60 mg m-2 VP-16 in both arms. Of the 13 patients who received more than two cycles, two out of five achieved partial response (PR) at the first level of arm A and one out of four achieved PR at the second level of arm B. We conclude that these schedules of sequential CPT-11 and VP-16 administration were inappropriate because of severe toxicities.
我们对转移性非小细胞肺癌未经治疗的患者进行了一项伊立替康（CPT-11）和依托泊苷（VP-16）序贯给药的I期研究。A组：第1 - 3天，CPT-11在90分钟内给药，第4 - 6天，VP-16在60分钟内给药。B组：第1 - 3天给予VP-16，第4 - 6天给予CPT-11。所有患者在第7 - 17天每天给予粒细胞集落刺激因子（G-CSF）。27例患者随机进入两组。A组和B组的主要剂量限制性毒性为粒细胞减少和腹泻。两组均观察到转氨酶和胆红素的短暂升高。两组毒性程度无差异。两组的最大耐受剂量（MTDs）均为CPT-11 60 mg/m²和VP-16 60 mg/m²。在接受两个以上周期治疗的13例患者中，A组第一剂量水平的5例中有2例达到部分缓解（PR），B组第二剂量水平的4例中有1例达到PR。我们得出结论，由于严重毒性，这些CPT-11和VP-16序贯给药方案不合适。
