Marx G, Lewis C, Hall K, Levi J, Ackland S
Department of Medical Oncology, Prince of Wales Hospital, Sydney, NSW, Australia.
Br J Cancer. 2002 Oct 7;87(8):846-9. doi: 10.1038/sj.bjc.6600542.
The aim of this study was to determine the maximum tolerated dose of a fixed dose of docetaxel when combined with continuous infusion ifosfamide, with and without G-CSF support, in the treatment of advanced cancer, and to evaluate anti-tumour activity of this combination. Thirty-one patients with advanced malignancies were treated with docetaxel 75 mg/m(2) intravenously on days 1, and ifosfamide at increasing dose levels from 1500 mg/m(2)/day to 2750 mg/m(2)/day as a continuous infusion from day 1-3, every 3 weeks. A total of 107 cycles of treatment were administered. Without G-CSF support dose-limiting toxicity of grade 4 neutropenia greater than 5 days duration occurred at dose level 1. With the addition of G-CSF the maximum tolerated dose was docetaxel 75 mg/m(2) on day 1 and ifosfamide 2750 mg/m(2)/day on days 1-3. Dose limiting toxicity (DLT) included ifosfamide-induced encephalopathy, febrile neutropenia and grade three mucositis. Three complete responses and 3 partial responses were seen. This combination of docetaxel and infusional ifosfamide is feasible and effective. The recommended dose for future phase II studies is docetaxel 75 mg/m(2) on day 1 and ifosfamide 2500 mg/m(2)/day continuous infusion on days 1-3.
本研究的目的是确定多西他赛固定剂量与持续输注异环磷酰胺联合使用时，在有或无粒细胞集落刺激因子（G-CSF）支持的情况下，治疗晚期癌症的最大耐受剂量，并评估该联合用药的抗肿瘤活性。31例晚期恶性肿瘤患者在第1天静脉注射多西他赛75mg/m²，异环磷酰胺剂量从1500mg/m²/天递增至2750mg/m²/天，于第1 - 3天持续输注，每3周重复一次。共进行了107个周期的治疗。在无G-CSF支持的情况下，剂量水平1出现了持续超过5天的4级中性粒细胞减少的剂量限制性毒性。添加G-CSF后，最大耐受剂量为第1天多西他赛75mg/m²，第1 - 3天异环磷酰胺2750mg/m²/天。剂量限制性毒性（DLT）包括异环磷酰胺引起的脑病、发热性中性粒细胞减少和3级粘膜炎。观察到3例完全缓解和3例部分缓解。多西他赛与输注用异环磷酰胺的这种联合用药是可行且有效的。未来II期研究的推荐剂量为第1天多西他赛75mg/m²，第1 - 3天异环磷酰胺2500mg/m²/天持续输注。
