Pronk L C, Schrijvers D, Schellens J H, de Bruijn E A, Planting A S, Locci-Tonelli D, Groult V, Verweij J, van Oosterom A T
Rotterdam Cancer Institute (Dr Daniel den Hoed Kliniek) and University Hospital Rotterdam, The Netherlands.
Br J Cancer. 1998;77(1):153-8. doi: 10.1038/bjc.1998.24.
Docetaxel and ifosfamide have shown significant activity against a variety of solid tumours. This prompted a phase I trial on the combination of these drugs. This phase I study was performed to assess the feasibility of the combination, to determine the maximum tolerated dose (MTD) and the side effects, and to propose a safe schedule for further phase II studies. A total of 34 patients with a histologically confirmed solid tumour, who were not pretreated with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-h infusion followed by ifosfamide as a 24-h infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg m(-2) and ifosfamide doses from 2.5 to 5.0 g m(-2). Granulocytopenia grade 3 and 4 were common (89%), short lasting and ifosfamide dose dependent. Febrile neutropenia and sepsis occurred in 17% and 2% of courses respectively. Non-haematological toxicities were mild to moderate and included alopecia, nausea, vomiting, mucositis, diarrhoea, sensory neuropathy, skin and nail toxicity and oedema. There did not appear to be any pharmacokinetic interaction between docetaxel and ifosfamide. One complete response (CR) (soft tissue sarcoma) and two partial responses (PRs) were documented. A dose of 75 mg m(-2) of docetaxel combined with 5.0 g m(-2) ifosfamide appeared to be manageable. Schedule A was advocated for further treatment.
多西他赛和异环磷酰胺已显示出对多种实体瘤有显著活性。这促使开展了一项关于这两种药物联合使用的I期试验。进行这项I期研究是为了评估联合用药的可行性，确定最大耐受剂量（MTD）和副作用，并为进一步的II期研究提出安全的用药方案。共有34例经组织学确诊的实体瘤患者进入该研究，这些患者未接受过紫杉烷类或异环磷酰胺预处理，且晚期疾病接受的化疗不超过一线。治疗方案为多西他赛静脉滴注1小时，随后异环磷酰胺静脉滴注24小时（方案A），或异环磷酰胺后接多西他赛（方案B），每3周一次。多西他赛剂量范围为60至85mg/m²，异环磷酰胺剂量范围为2.5至5.0g/m²。3级和4级粒细胞减少很常见（89%），持续时间短且与异环磷酰胺剂量有关。发热性中性粒细胞减少和败血症分别发生在17%和2%的疗程中。非血液学毒性为轻至中度，包括脱发、恶心、呕吐、粘膜炎、腹泻、感觉神经病变、皮肤和指甲毒性以及水肿。多西他赛和异环磷酰胺之间似乎没有任何药代动力学相互作用。记录到1例完全缓解（CR）（软组织肉瘤）和2例部分缓解（PR）。多西他赛75mg/m²联合异环磷酰胺5.0g/m²的剂量似乎是可耐受的。主张采用方案A进行进一步治疗。
