Phase I Trial of High‐Dose Etoposide, High‐Dose Cisplatin, and Reinfusion of Autologous Bone Marrow for Lung Cancer
Phase I Trial of High‐Dose Etoposide, High‐Dose Cisplatin, and Reinfusion of Autologous Bone Marrow for Lung Cancer
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大剂量依托泊苷、大剂量顺铂和自体骨髓回输治疗肺癌的 I 期试验
DOI：
10.1097/00000421-199004000-00004
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
R. Creger
中科院分区：
文献类型：
--
作者：
H. Lazarus;T. Spitzer;R. Creger
我们对29名复发或难治性小细胞和非小细胞肺癌患者进行了I期试验，使用固定剂量的顺铂，增加剂量的依托泊苷，并回输先前获得的自体骨髓。中位年龄59岁(38-68岁)。3名患者为小细胞肺癌，26名患者为非小细胞肺癌。患者接受静脉注射。顺铂200 mg/m2，连用5天，静脉滴注。依托泊苷600 mg/m2/天，共3天(共1,800 mg/m2)，随后分别升至800、1,000、1.200、1,400和1,600 mg/m2/天，共3天(共2,400-4,800 mg/m2)。化疗结束后第二天，冷冻保存的自体骨髓经中心静脉导管解冻后回输。毒副作用包括恶心、呕吐、脱发、高音听力丧失、粘膜炎、腹泻、肾功能不全、代谢性酸中毒和严重的骨髓抑制。中性粒细胞减少(<500中性粒细胞/μL)持续时间5~22天(中位数11天)，严重血小板减少(血小板<20,000/μL未输血)2~19天(中位数9天)。完成治疗的4名患者出现可逆性肾功能不全(峰值血肌酐分别为6.7、6.6、4.3和3.5 mg/dl)。在3例患者中，死亡发生在化疗和骨髓移植后4周内。3例完全缓解，12例部分缓解(1+~22+个月，中位数3个月)。8名患者无反应，2名患者移植后1个月内肿瘤进展。依托泊苷的最大耐受量为1400 mg/m2/天(共4200 mg/m2)。因为三名患者中有两名在每天1.600毫克/平方米(总计4,800毫克/平方米)的剂量下出现了危及生命的腹泻。该方案令人鼓舞的抗肿瘤效果表明，该方法可能是治疗肺癌和其他对VP-16和顺铂敏感的肿瘤的有效方法。
We undertook a phase I trial using fixed-dose cisplatin, escalating doses of etoposide, and reinfusion of previously obtained autologous bone marrow in 29 relapsed or refractory small cell and non-small-cell lung cancer patients. Median age was 59 years (range of 38–68 years). Three patients had small-cell and 26 patients had non-small-cell lung cancer. Patients received i.v. cisplatin 200 mg/m2 over 5 days and i.v. etoposide 600 mg/m2/day for 3 days (total of 1,800 mg/ m2) that was escalated to 800, 1,000, 1.200, 1,400, and 1,600 mg/m2/day for 3 days (total of 2,400–4,800 mg/m2). Cryopreserved autologous bone marrow was thawed and reinfused through a central venous catheter the second day after the completion of chemotherapy. Toxicities included nausea, vomiting, alopecia, high-tone hearing loss, mucositis, diarrhea, renal insufficiency, metabolic acidosis, and severe myelosuppression. The duration of neutropenia (less than 500 neutrophils/μl) ranged from 5 to 22 days (median of 11 days) and the duration of severe thrombocytopenia (platelets of less than 20,000/μl untransfused) ranged from 2 to 19 days (median of 9 days). Reversible renal insufficiency (peak serum creatinines of 6.7, 6.6, 4.3, and 3.5 mg/dl) occurred in four patients who completed the therapy. In three patients, death occurred within 4 weeks of chemotherapy and marrow rein- fusion. Three complete and 12 partial remissions (range of 1 + – 22 + months, median of 3 months) were observed. No response was noted in eight patients and tumor progression within I month of transplant occurred in two patients. The maximally tolerated dose of etoposide was 1,400 mg/m2/day (total of 4,200 mg/m2). since two of three patients developed life-threatening diarrhea at the 1.600 mg/m2/day (total of 4,800 mg/m2) dose. The encouraging antitumor effects of this regimen suggest that this approach may be useful therapy for lung cancer and other tumors sensitive to VP-16 and cisplatin.