Rathmann J, Leopold K A, Rigas J R
Thoracic Oncology Program, Norris Cotton Cancer Center, Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756-0001, USA.
Semin Radiat Oncol. 1999 Apr;9(2 Suppl 1):130-5.
Platinum-based combination chemotherapy plus thoracic radiation prolongs survival for patients with stage III non-small cell lung cancer. Paclitaxel demonstrates significant clinical antitumor activity in this disease and potentiates the effects of ionizing radiation by arresting cells at the sensitive G2/M cell cycle phase. The optimal schedule of paclitaxel administered concomitantly with thoracic radiation has not been established. The preliminary results of this phase I trial, which was designed to define the dose-limiting adverse event and the maximum tolerated dose of paclitaxel administered daily before each fraction of thoracic radiation, are being presented. Twenty-nine patients with inoperable clinical stage II to IIIB non-small cell lung cancer received two 21-day cycles of primary chemotherapy with carboplatin and paclitaxel. Six weeks from the initiation of therapy, daily paclitaxel was administered intravenously over 1 hour without premedication before 68 Gy of thoracic radiation in 34 fractions. Twenty-six patients completed concomitant daily paclitaxel with radiation and are evaluable for toxicity. Early radiation esophagitis was the dose-limiting toxicity at the 15 mg dose level. A daily paclitaxel dose of 10 mg or 6 mg/m2 and 68 Gy of thoracic radiotherapy are recommended for further study. Preliminary data from this dose-escalation trial suggest that this combined modality treatment with concurrent radiation and daily paclitaxel following primary induction therapy for stage II to III non-small cell lung cancer is feasible. The observed adverse effects within the radiation field suggest active radiosensitization by low-dose daily paclitaxel.
铂类联合化疗加胸部放疗可延长Ⅲ期非小细胞肺癌患者的生存期。紫杉醇在该疾病中显示出显著的临床抗肿瘤活性，并通过将细胞阻滞在敏感的G2/M细胞周期阶段增强电离辐射的效果。紫杉醇与胸部放疗同时给药的最佳方案尚未确定。本Ⅰ期试验的初步结果正在公布，该试验旨在确定胸部放疗每次分割前每日给予紫杉醇的剂量限制性不良事件和最大耐受剂量。29例无法手术的临床Ⅱ期至ⅢB期非小细胞肺癌患者接受了两个21天周期的卡铂和紫杉醇一线化疗。从治疗开始6周后，在34次分割给予68 Gy胸部放疗前，每日紫杉醇静脉输注1小时，不进行预处理。26例患者完成了紫杉醇与放疗同步治疗，可评估毒性。15 mg剂量水平时，早期放射性食管炎是剂量限制性毒性。推荐进一步研究每日紫杉醇剂量为10 mg或6 mg/m²及68 Gy胸部放疗。该剂量递增试验的初步数据表明，对Ⅱ期至Ⅲ期非小细胞肺癌进行诱导治疗后，同步放疗和每日紫杉醇的这种联合治疗方式是可行的。在放疗区域内观察到的不良反应提示低剂量每日紫杉醇具有有效的放射增敏作用。
