Saeter G, Talle K, Solheim O P
Department of Medical Oncology and Radiotherapy, Norwegian Radium Hospital, Oslo.
Cancer Chemother Pharmacol. 1995;36(2):172-5. doi: 10.1007/BF00689204.
A total of 33 patients (median age, 44 years) with high-grade, adult soft-tissue sarcoma were treated with etoposide given at 600 mg/m2 in a 72-h continuous infusion and ifosfamide given at 1500 mg/m2 per day for 3 days every 3 weeks. Dose escalation/reduction was protocolled depending on the level of hematological toxicity observed in the preceding course. Overall, 90% of patients had metastatic disease, and the most common histologies were malignant fibrous histiocytoma and leiomyosarcoma. A median of 5 (range, 1-9) courses were given. Of 30 patients who were evaluable for response, 12 (40%) obtained a partial remission, and the median time to progression was 8 (range, 4-13) months. Grade 3-4 leukopenia and thrombocytopenia were seen after 89% and 8% of the courses, respectively; neutropenic fever was seen in half of the patients (15% of courses); and 32% of courses had to be postponed by 7 days or more due to myelosuppression. Dose reduction to below the standard had to be performed in 46% of courses, and dose escalation was achieved in only 13%. The reduced toxicity seen after the addition of granulocyte colony-stimulating factor (G-CSF) in five patients indicates that growth-factor support may enhance the dose intensity of the regimen. The results indicate significant activity for this regimen in adult soft-tissue sarcoma, which may in part be a result of the escalated dose and prolonged mode of administration of the phase-specific agent etoposide. As a result of this pilot series, a phase II study with ifosfamide, etoposide, and G-CSF in advanced adult soft-tissue sarcoma has been initiated by the Scandinavian Sarcoma Group.
共有33例（中位年龄44岁）高级别成人软组织肉瘤患者接受了依托泊苷治疗，剂量为600mg/m²，持续静脉输注72小时，异环磷酰胺剂量为1500mg/m²，每日1次，连用3天，每3周重复。根据前一疗程观察到的血液学毒性水平进行剂量递增/递减。总体而言，90%的患者有转移性疾病，最常见的组织学类型为恶性纤维组织细胞瘤和平滑肌肉瘤。中位疗程数为5个（范围1 - 9个）。在30例可评估疗效的患者中，12例（40%）获得部分缓解，中位疾病进展时间为8个月（范围4 - 13个月）。分别有89%和8%的疗程出现3 - 4级白细胞减少和血小板减少；半数患者（15%的疗程）出现中性粒细胞减少性发热；32%的疗程因骨髓抑制不得不推迟7天或更长时间。46%的疗程需要将剂量减至标准剂量以下，仅13%的疗程实现了剂量递增。在5例患者中加用粒细胞集落刺激因子（G - CSF）后毒性降低，表明生长因子支持可能提高该方案的剂量强度。结果表明该方案对成人软组织肉瘤有显著活性，这可能部分归因于细胞周期特异性药物依托泊苷的剂量递增和给药方式延长。基于这一初步系列研究，斯堪的纳维亚肉瘤研究组启动了一项关于异环磷酰胺、依托泊苷和G - CSF用于晚期成人软组织肉瘤的Ⅱ期研究。
