Mertens W C, Eisenhauer E A, Jolivet J, Ernst S, Moore M, Muldal A
London Regional Cancer Centre.
Ann Oncol. 1994 Feb;5(2):185-7. doi: 10.1093/oxfordjournals.annonc.a058776.
Most patients diagnosed with renal carcinoma developed metastatic disease at some time during their course, with available therapy inducing response in only a small proportion of patients. Docetaxel (Taxotere, RP56976) a semi-synthetic analogue of paclitaxel with a broad range of in vitro antitumor activity, was evaluated in a phase II study.
Eligibility criteria included histologically proven metastatic or advanced, bidimensionally measurable disease, no prior chemotherapy, immunotherapy, or hormonal therapy, adequate hematologic (neutrophils > or = 2.0 x 10(9)/L, platelets > or = 100 x 10(9)/L) and biochemical (serum creatinine and bilirubin < or = 1.5 x normal, transaminases < or = 3 x normal) parameters, WHO performance status of at least 2, and a life expectancy of > 12 weeks. Docetaxel was administered in a dose of 100 mg/m2 as a 1 hour intravenous infusion every 3 weeks. The first 2 patients entered onto the study were not premedicated for hypersensitivity reactions; subsequent patients received dexamethasone 10 mg and diphenhydramine 50 mg i.v. 30 minutes prior to docetaxel.
Twenty patients were entered onto the study, with 2 considered inevaluable for response. Sixty cycles of therapy were administered, with only 2 cycles delivered at a dose of 55 mg/m2 or less. No objective responses were seen; 1 patient demonstrated a mixed response. Neutropenia was significant, with 42/60 cycles developing grade 3/4 granulocytopenia. Fifty-five percent of patients demonstrated hypersensitivity reactions despite the premedication regimen employed, higher than that of the phase I studies which established the dose and schedule used in this trial.
大多数被诊断为肾癌的患者在病程中的某个阶段会发生转移性疾病，现有治疗方法仅能使一小部分患者产生反应。多西他赛（泰索帝，RP56976）是紫杉醇的半合成类似物，具有广泛的体外抗肿瘤活性，在一项II期研究中对其进行了评估。
入选标准包括组织学证实的转移性或晚期、二维可测量疾病，未曾接受过化疗、免疫治疗或激素治疗，血液学指标（中性粒细胞≥2.0×10⁹/L，血小板≥100×10⁹/L）和生化指标（血清肌酐和胆红素≤1.5倍正常上限，转氨酶≤3倍正常上限）正常，世界卫生组织体力状况评分至少为2分，预期寿命>12周。多西他赛以100mg/m²的剂量每3周静脉输注1小时给药。最初进入研究的2例患者未进行过敏反应预处理；随后的患者在多西他赛给药前30分钟静脉注射10mg地塞米松和50mg苯海拉明。
20例患者进入研究，其中2例因反应不可评估。共进行了60个周期的治疗，只有2个周期的剂量为55mg/m²或更低。未观察到客观反应；1例患者表现为混合反应。中性粒细胞减少明显，60个周期中有42个周期出现3/4级粒细胞减少。尽管采用了预处理方案，但仍有55%的患者出现过敏反应，高于确定本试验所用剂量和方案的I期研究。
1）多西他赛对晚期肾癌无效。2）过敏反应发生率高表明在此剂量水平需要更强化的预处理和/或更慢的输注时间。
