Eguchi K, Etou H, Miyachi S, Morinari H, Nakada K, Noda K, Ohkuni Y, Watanabe K, Yamada Y, Ohe Y
Department of Internal Medicine and Thoracic Oncology, National Cancer Center, Tokyo, Japan.
Eur J Cancer. 1994;30A(2):188-94. doi: 10.1016/0959-8049(94)90085-x.
A dose escalation study of teniposide (VM-26) plus cisplatin (CDDP) was carried out using recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 46 previously untreated patients with advanced small cell lung cancer (SCLC). The dose of CDDP was 80 mg/m2/day intravenously (i.v.) (day 1) and VM-26 was escalated from 60 mg/m2/day to 80, 100 and 120 mg/m2/day i.v. x 5 days for four cycles. The dose of rhG-CSF was 90 micrograms/m2/day subcutaneously for 13 days. The feasibility of the regimen at the starting dose level of VM-26 with or without rhG-CSF was initially examined in 10 patients chosen through random allocation. WHO grade 4 neutropenia was observed in 17% (three out of 18 courses) of patients in the rhG-CSF group and in 63% (12 out of 19 courses) of the control group (P < 0.01). The number of patients with febrile episodes (> 38 degrees C) over the four courses of chemotherapy was 1 in the rhG-CSF group and 4 in the control group. According to these results, all 36 patients received rhG-CSF in the dose escalation stage. The incidence of WHO grade 4 neutropenia at the dose levels of 60, 80, 100 and 120 mg/m2/day of VM-26 was 66, 57, 76 and 85%, respectively (P > 0.1). The incidence of grade 4 thrombocytopenia was 19, 31, 18 and 46%, respectively (P > 0.1). The overall response rate was 100% in patients with limited stage SCLC and 83% in patients with extensive stage SCLC. The actual administered VM-26 dose per week at the dose level of 100 mg/m2/day was 1.6-fold higher than the planned starting dose (60 mg/m2/day) per week. At the dose level of 120 mg/m2/day, 50% of patients developed WHO grade 4 leucopenia, which lasted longer than 1 week and 67% of the patients had WHO grade 3 or 4 diarrhoea. At this same dose, all patients had at least one febrile episode (> 38 degrees C), and 1 patient died of cerebral bleeding with severe thrombocytopenia. The median survival time of all patients was 451 days (411 days, extensive disease; 497 days, limited disease). VM-26 plus CDDP with rhG-CSF was active in previously untreated patients with SCLC. The recommended dose of VM-26 in combination with CDDP for a phase II study is 100 mg/m2/day for 5 days with rhG-CSF support.
对46例既往未接受过治疗的晚期小细胞肺癌（SCLC）患者，使用重组人粒细胞集落刺激因子（rhG-CSF）进行了替尼泊苷（VM-26）加顺铂（CDDP）的剂量递增研究。CDDP剂量为80mg/m²/天静脉滴注（第1天），VM-26剂量从60mg/m²/天递增至80、100和120mg/m²/天静脉滴注，共5天，进行4个周期。rhG-CSF剂量为90μg/m²/天皮下注射，共13天。最初通过随机分配选择10例患者，研究了VM-26起始剂量水平联合或不联合rhG-CSF方案的可行性。rhG-CSF组17%（18个疗程中的3个）的患者出现世界卫生组织（WHO）4级中性粒细胞减少，而对照组为63%（19个疗程中的12个）（P<0.01）。化疗4个疗程中发热发作（>38℃）的患者数量，rhG-CSF组为1例，对照组为4例。根据这些结果，36例患者在剂量递增阶段均接受了rhG-CSF。VM-26剂量水平为60、80、100和120mg/m²/天的WHO 4级中性粒细胞减少发生率分别为66%、57%、76%和85%（P>0.1）。4级血小板减少发生率分别为19%、31%、18%和46%（P>0.1）。局限期SCLC患者的总缓解率为100%，广泛期SCLC患者为83%。在100mg/m²/天剂量水平，实际每周给予的VM-26剂量比计划起始剂量（60mg/m²/天）高1.6倍。在120mg/m²/天剂量水平，50%的患者出现WHO 4级白细胞减少，持续时间超过1周，67%的患者出现WHO 3级或4级腹泻。同样在该剂量下，所有患者至少有一次发热发作（>38℃），1例患者死于严重血小板减少伴脑出血。所有患者的中位生存时间为451天（广泛期疾病为411天；局限期疾病为497天）。VM-26加CDDP联合rhG-CSF对既往未接受过治疗的SCLC患者有效。VM-26联合CDDP用于II期研究的推荐剂量为100mg/m²/天，共5天，并给予rhG-CSF支持。
