van der Gaast A, Kok T C, Kerkhofs L, Siersema P D, Tilanus H W, Splinter T A
Department of Medical Oncology, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands.
Br J Cancer. 1999 Jun;80(7):1052-7. doi: 10.1038/sj.bjc.6690462.
We performed this dose-finding study with a fixed dose of cisplatin and increasing doses of paclitaxel given every 2 weeks to determine the maximum tolerable dose of this schedule. Sixty-four patients with advanced oesophageal cancer were treated with a cisplatin dose of 60 mg m(-2) and increasing doses of paclitaxel from 100 mg m(-2) up to 200 mg m(-2) both administered over 3 h for a maximum of six cycles in patients with stable disease or eight cycles in responding patients. Patients were retreated when the granulocytes were > 0.75 x 10(9) l(-1) and the platelets > 75 x 10(9) l(-1). The dose of paclitaxel could be increased to 200 mg m(-2) without encountering dose limiting haematological toxicity. At the dose levels 190 mg m(-2) and 200 mg m(-2) of paclitaxel cumulative sensory neurotoxicity became the dose-limiting toxicity. The dose intensity of paclitaxel calculated over six cycles rose from 50 mg m(-2) per week to 85 mg m(-2) per week. Only three episodes of granulocytopenic fever were encountered out of a total of 362 cycles of treatment. Of the 59 patients evaluable for response, 31 (52%) had a partial or complete response. In a biweekly schedule with a fixed dose of 60 mg m(-2) cisplatin it is possible to increase the dose of paclitaxel to 180 mg m(-2). At higher dose levels, neurotoxicity becomes the dose-limiting toxicity. The observed response rate warrants further investigation of this schedule.
我们进行了这项剂量探索研究，每2周给予固定剂量的顺铂和递增剂量的紫杉醇，以确定该方案的最大耐受剂量。64例晚期食管癌患者接受了60mg/m²的顺铂剂量，并给予递增剂量的紫杉醇，从100mg/m²至200mg/m²，两种药物均在3小时内给药，病情稳定的患者最多接受6个周期治疗，有反应的患者最多接受8个周期治疗。当粒细胞计数>0.75×10⁹/L且血小板计数>75×10⁹/L时，患者可再次接受治疗。紫杉醇剂量可增至200mg/m²，而未出现剂量限制性血液学毒性。在紫杉醇剂量为190mg/m²和200mg/m²时，累积感觉神经毒性成为剂量限制性毒性。计算得出的六个周期内紫杉醇的剂量强度从每周50mg/m²升至每周85mg/m²。在总共362个治疗周期中，仅出现3次粒细胞减少性发热。在59例可评估反应的患者中，31例（52%）有部分或完全反应。在每2周一次的方案中，给予固定剂量60mg/m²的顺铂时，可将紫杉醇剂量增至180mg/m²。在更高剂量水平时，神经毒性成为剂量限制性毒性。观察到的反应率值得对该方案进行进一步研究。
