Allal Abdelkarim S, Zwahlen Daniel, Becker Minerva, Dulguerov Pavel, Mach Nicolas
Division of Radiation Oncology, Geneva University Hospitals, Geneva, Switzerland.
Cancer J. 2006 Jan-Feb;12(1):63-8. doi: 10.1097/00130404-200601000-00011.
This study was conducted to determine the maximum tolerated dose of docetaxel when administered concomitantly with radical hyperfractionated radiotherapy and cisplatin in patients with locally advanced head and neck cancer.
Patients with stage III-IV tumors received radical radiotherapy of 74.4 Gy given in two daily fractions of 1.2 Gy for 6 weeks. Cisplatin was given once weekly on day 1 at a constant dose of 15 mg/m2. The starting dose of docetaxel was 10 mg/m2 once weekly on day 3, with planned escalation steps of 5 mg/m2. Main endpoints of the study were the maximum tolerated dose of docetaxel, acute toxicities, and the preliminary efficacy results.
Twenty-five patients were enrolled. Median follow-up was 15 months (range: 4-40 months). Two of three patients presented with dose-limiting toxicities at the 15-mg/m2 dose of docetaxel (one patient presented with multiple grade 3-4 toxicities requiring hospitalization for management and another presented with multiple toxicities including life-threatening bronchoaspiration). Thus, the weekly docetaxel dose of 10 mg/m2 was considered the maximum tolerated dose. Nineteen patients were then treated with the maximum tolerated dose and no dose-limiting toxicities were observed. Radiotherapy was completed in all patients except one (median dose: 74.4; range: 73.2-74.4), and at least 80% of the scheduled cisplatin and docetaxel doses were given in 92% of the patients. Acute toxicities were dominated by grade 3 mucositis (92%) and grade 3-4 dysphagia (68%). The 2.5 year actuarial local control rate was 87.5%, and the disease-free survival rate was 75%. At the time of last follow-up, 23 patients were alive and two had died from cancer. No distant metastases were observed.
In patients with locally advanced head and neck cancer, this study determined the maximum tolerated dose of docetaxel to be 10 mg/m2 administered once weekly when given concurrently with 74.4 Gy hyperfractionated radiotherapy and a weekly 15-mg/m2 dose of cisplatin. The toxicity profile and the encouraging results suggest that this new combination merits further investigation in a multi-institutional phase II trial.
本研究旨在确定多西他赛与根治性超分割放疗和顺铂联合应用于局部晚期头颈癌患者时的最大耐受剂量。
Ⅲ - Ⅳ期肿瘤患者接受6周的根治性放疗，每日分两次给予，每次1.2 Gy，总剂量74.4 Gy。顺铂在第1天每周给药一次，固定剂量为15 mg/m²。多西他赛的起始剂量为第3天每周一次10 mg/m²，计划以5 mg/m²的步长递增。本研究的主要终点为多西他赛的最大耐受剂量、急性毒性及初步疗效结果。
共纳入25例患者。中位随访时间为15个月（范围：4 - 40个月）。在多西他赛剂量为15 mg/m²时，三名患者中有两名出现剂量限制性毒性（一名患者出现多种3 - 4级毒性反应，需要住院治疗；另一名患者出现多种毒性反应，包括危及生命的支气管误吸）。因此，多西他赛每周剂量10 mg/m²被认为是最大耐受剂量。随后19例患者接受最大耐受剂量治疗，未观察到剂量限制性毒性。除一名患者外，所有患者均完成放疗（中位剂量：74.4；范围：73.2 - 74.4），92%的患者至少接受了计划的顺铂和多西他赛剂量的80%。急性毒性以3级黏膜炎（92%）和3 - 4级吞咽困难（68%）为主。2.5年的精算局部控制率为87.5%，无病生存率为75%。在最后一次随访时，23例患者存活，2例死于癌症。未观察到远处转移。
在局部晚期头颈癌患者中，本研究确定多西他赛与74.4 Gy超分割放疗及每周15 mg/m²顺铂联合应用时，最大耐受剂量为每周一次10 mg/m²。毒性特征和令人鼓舞的结果表明，这种新的联合方案值得在多机构II期试验中进一步研究。
