Bunnell C A, Thompson L, Buswell L, Berkowitz R, Muto M, Sheets E, Shulman L N
Hematology-Oncology Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Cancer. 1998 Feb 1;82(3):561-6. doi: 10.1002/(sici)1097-0142(19980201)82:3<561::aid-cncr19>3.0.co;2-#.
Ifosfamide and paclitaxel are antineoplastic agents with broad activity and with different mechanisms of action. A Phase I trial was conducted to determine the maximum tolerated dose and associated toxicities of these agents when used in combination.
Patients with refractory, incurable solid tumors were entered on a 5-step Phase I trial of ifosfamide, given in doses of 2-3 g/m2 intravenous (i.v.) bolus for 3 days with mesna support, and paclitaxel, given in doses of 135-190 g/m2 i.v. by continuous infusion over 24 hours. Paclitaxel was given after the first dose of ifosfamide on Day 1.
Twenty-three patients were treated, and the maximum tolerated dose was the highest planned dose level of the trial: ifosfamide, 3 g/m2/day i.v. for 3 days, and paclitaxel, 190 mg/m2 i.v. over 24 hours. Hematologic toxicity was not dose-limiting, and although neutropenia occurred, it was brief (median, 2-4 days) and resulted in hospitalization for neutropenia and fever in only 7 of 111 courses of therapy. For patients treated at the highest dose level, only 1 of 50 courses of therapy resulted in hospitalization for neutropenia and fever. Nonhematologic toxicity also was not severe and no significant neuropathy occurred. Although patients entered into the study were heavily pretreated, responses were observed, particularly in patients with breast or ovarian carcinoma.
Ifosfamide and paclitaxel can be administered safely in the doses used in this study and there are indications of significant antitumor effect. Further studies are necessary to explore the antineoplastic activity of this regimen, particularly for patients with breast and ovarian carcinoma.
异环磷酰胺和紫杉醇是具有广泛活性且作用机制不同的抗肿瘤药物。进行了一项I期试验，以确定这些药物联合使用时的最大耐受剂量及相关毒性。
难治性、不可治愈的实体瘤患者进入异环磷酰胺的5步I期试验，剂量为2 - 3 g/m²静脉推注，持续3天，并给予美司钠支持；紫杉醇剂量为135 - 190 mg/m²静脉滴注，持续24小时。紫杉醇在第1天的第一剂异环磷酰胺之后给予。
23例患者接受了治疗，最大耐受剂量为试验计划的最高剂量水平：异环磷酰胺，3 g/m²/天静脉滴注，持续3天；紫杉醇，190 mg/m²静脉滴注，持续24小时。血液学毒性不是剂量限制性的，尽管发生了中性粒细胞减少，但持续时间短暂（中位时间为2 - 4天），在111个疗程的治疗中，仅7例因中性粒细胞减少和发热而住院。在最高剂量水平接受治疗的患者中，50个疗程的治疗中仅有1例因中性粒细胞减少和发热而住院。非血液学毒性也不严重，未发生明显的神经病变。尽管入组研究的患者之前接受过大量治疗，但仍观察到了反应，尤其是在乳腺癌或卵巢癌患者中。
异环磷酰胺和紫杉醇可以按照本研究中使用的剂量安全给药，并且有显著抗肿瘤作用的迹象。有必要进一步研究该方案的抗肿瘤活性，特别是对于乳腺癌和卵巢癌患者。
