Vogt H G, Kolotas C, Martin T, Schneider L V, Goes-Schmieder R, Mitrou P S, Diergarten K, Kober B, Zamboglou N
Department of Radiation Medicine, Städtische Kliniken Offenbach, Germany.
Semin Oncol. 1996 Dec;23(6 Suppl 16):120-3.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most active single agents for the treatment of non-small cell lung cancer, with response rates of 21% to 24%. We present a phase I study with paclitaxel and simultaneous radiation in previously untreated, locally advanced, inoperable, stage IIIA/B non-small cell lung cancer. The aims of the study were to determine the maximum tolerated dose, define the safety and toxicity, and obtain preliminary data about the activity of the combined modality. Patients received a fixed dose of radiotherapy (1.8 Gy/d, 5 days a week for 6.5 weeks, for a total dose of 59.4 Gy) and concomitant chemotherapy with paclitaxel 45 mg/m2 days 1, 8, and 15 in level 1; days 1, 8, 15, 22, and 29 in level 2; and days 1, 8, 15, 22, 29, 36, and 43 in level 3. The paclitaxel dosage was increased to 55 mg/m2 on days 1, 8, 15, 22, 29, 36, and 43 in level 4. Paclitaxel was administered as a 3-hour continuous intravenous infusion. Dexamethasone, clemastine, and ranitidine were given for hypersensitivity prophylaxis. Twenty-two patients (18 men and four women) entered the study; their median age was 66.5 years (age range, 38 to 74 years). Disease stage was IIIA in six of 22 patients and stage IIIB in 16. Six patients were treated at level 1, five at level 2, five at level 3, and six at level 4. There were 18 patients evaluable for toxicity and response. Side effects generally were moderate during the treatment period. One patient withdrew by request after the first course, one patient died of tumor bleeding after five courses, one patient died of progressive disease (lymphangiosis carcinomatosa of both lungs) after the sixth course, and one patient is too early for evaluation. Among the 18 patients evaluable for response, there were one complete and 10 partial remissions; seven patients reached a minor response. It is concluded that the therapy was well tolerated in these patients. Importantly, no severe adverse events were observed that could be associated with paclitaxel or radiotherapy. This combined modality appears to be a practicable and effective treatment of non-small cell lung cancer. The maximum tolerated dose has not yet been reached, and dose escalation is planned.
紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）是治疗非小细胞肺癌最有效的单一药物之一，缓解率为21%至24%。我们开展了一项针对先前未接受过治疗、局部晚期、无法手术的IIIA/B期非小细胞肺癌患者的I期研究，采用紫杉醇与同步放疗联合治疗。该研究的目的是确定最大耐受剂量，明确安全性和毒性，并获取有关联合治疗方案活性的初步数据。患者接受固定剂量的放疗（1.8 Gy/天，每周5天，共6.5周，总剂量59.4 Gy），并在第1阶段于第1、8和15天同时接受45 mg/m²的紫杉醇化疗；第2阶段于第1、8、15、22和29天；第3阶段于第1、8、15、22、29、36和43天。在第4阶段，第1、8、15、22、29、36和43天的紫杉醇剂量增加至55 mg/m²。紫杉醇采用3小时持续静脉输注给药。给予地塞米松、氯马斯汀和雷尼替丁预防过敏反应。22例患者（18例男性和4例女性）进入研究；他们的中位年龄为66.5岁（年龄范围38至74岁）。22例患者中6例为IIIA期，16例为IIIB期。6例患者在第1阶段接受治疗，5例在第2阶段，5例在第3阶段，6例在第4阶段。有18例患者可评估毒性和疗效。治疗期间副作用一般为中度。1例患者在第一疗程后请求退出，1例患者在五个疗程后死于肿瘤出血，1例患者在第六疗程后死于疾病进展（双肺淋巴管癌病），1例患者评估过早。在18例可评估疗效的患者中，有1例完全缓解，10例部分缓解；7例患者达到轻微缓解。结论是这些患者对该治疗耐受性良好。重要的是，未观察到与紫杉醇或放疗相关的严重不良事件。这种联合治疗方案似乎是一种可行且有效的非小细胞肺癌治疗方法。尚未达到最大耐受剂量，计划进行剂量递增。
