Belani C P, Aisner J, Bahri S, Jett J, Day R, Capazolli M J, Hiponia D, Engstrom C
Department of Medicine, University of Pittsburgh School of Medicine and the University of Pittsburgh Cancer Institute, PA 15213, USA.
Semin Oncol. 1996 Dec;23(6 Suppl 16):113-6.
Based on superior results observed with combined-modality therapy over radiotherapy alone and on the authors' previous work with carboplatin and standard daily thoracic radiotherapy in patients with advanced, unresectable non-small cell lung cancer, a phase II study was designed to incorporate radiosensitizing doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) into the carboplatin/radiotherapy regimen, to improve the therapeutic index and define the toxicities. Thirty-two patients have been entered. Paclitaxel 45 mg/m2/wk was administered over 3 hours prior to carboplatin (100 mg/m2/wk) and thoracic radiotherapy (1.8 Gy/d 5 days a week; total dose, 60 to 65 Gy). No grade 4 toxicities occurred. Seven patients had chemotherapy doses delayed because of grade 3 neutropenia, and one patient had grade 3 mucositis/esophagitis that required hospitalization. Median survival has not yet been reached, and all patients are being followed. These preliminary data demonstrate the feasibility of combined concurrent chemoradiotherapy, with acceptable toxicities. Further investigation is needed to optimize carboplatin dosage with adaptive control using formulas based on pharmacokinetics and pharmacodynamics. Full-dose induction chemotherapy regimens to maximize the systemic effects of chemotherapy should precede concurrent chemoradiotherapy in future studies.
基于联合治疗相对于单纯放疗所观察到的更好结果，以及作者之前在晚期不可切除非小细胞肺癌患者中使用卡铂和标准每日胸部放疗的研究工作，设计了一项II期研究，将具有放射增敏剂量的紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）纳入卡铂/放疗方案，以提高治疗指数并明确毒性。已纳入32例患者。在给予卡铂（100mg/m²/周）和胸部放疗（1.8Gy/天，每周5天；总剂量60至65Gy）之前3小时，给予紫杉醇45mg/m²/周，持续3小时。未发生4级毒性反应。7例患者因3级中性粒细胞减少而化疗剂量延迟，1例患者出现3级粘膜炎/食管炎，需要住院治疗。中位生存期尚未达到，所有患者均在随访中。这些初步数据证明了同步放化疗联合应用的可行性，且毒性可接受。需要进一步研究，通过基于药代动力学和药效学的公式进行适应性控制来优化卡铂剂量。在未来的研究中，同步放化疗之前应采用全剂量诱导化疗方案，以最大化化疗的全身效应。
