Havemann K, Wolf M, Goerg C, Faoro C, Pfab R, Diergarten K
Department of Internal Medicine, Phillips-University Hospitals, Marburg, Germany.
Semin Oncol. 1995 Dec;22(6 Suppl 14):19-22.
In a clinical phase II trial, radiotherapy and escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) were given concurrently to patients with stage IIIA/B non-small cell lung cancer. Radiotherapy was given in daily doses of 2 Gy, 5 days a week, in weeks 1 to 3 and 6 to 8 for a total dose of 56 Gy. Paclitaxel was given in 3-hour infusions on day 1, also in weeks 1 to 3 and 6 to 8. The starting dose level was 50 mg/m2; the subsequent dose levels were 60, 72, 86, and 103 mg/m2. Cohorts of three to six patients were assigned to each dose level until intolerable toxicity (eg, World Health Organization grade 3 or 4 leukopenia) occurred in three of the six patients. Currently, 15 patients have entered the study. Twelve patients have finished the treatment protocol and are evaluable for toxicity and response. Hematologic toxicity was mild, and even at 86 mg/m2, the highest evaluable dose level, no severe myelosuppression was noticed. The main clinical toxicity was the occurrence of pulmonary infections, which were seen in five patients. One of these patients had a Pneumocystis carinii infection, but no pathogens were isolated from the four others with interstitial infections. Mild to moderate esophagitis was seen in five patients. All patients showed a decrease of tumor size. Four patients had a major response with nearly complete disappearance of radiologic tumor signs, five patients had a partial remission, and three patients experienced a minor response. Thus, the overall response rate was 75%. In summary, the maximum tolerated dose of paclitaxel has not yet been achieved, the occurrence of pulmonary infections represents the major clinical toxicity, and the extremely high response rate merits further clinical evaluation of this regimen.
在一项临床II期试验中，对IIIA/B期非小细胞肺癌患者同时给予放射治疗和递增剂量的紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）。放射治疗在第1至3周和第6至8周每周5天，每天剂量为2 Gy，总剂量为56 Gy。紫杉醇在第1天进行3小时静脉输注，同样在第1至3周和第6至8周。起始剂量水平为50 mg/m²；随后的剂量水平为60、72、86和103 mg/m²。每个剂量水平分配3至6名患者组成队列，直到6名患者中有3名出现不可耐受的毒性（如世界卫生组织3级或4级白细胞减少）。目前，已有15名患者进入该研究。12名患者完成了治疗方案，可对毒性和反应进行评估。血液学毒性较轻，即使在最高可评估剂量水平86 mg/m²时，也未发现严重的骨髓抑制。主要临床毒性是肺部感染的发生，有5名患者出现。其中1名患者发生卡氏肺孢子虫感染，但另外4名间质性感染患者未分离出病原体。5名患者出现轻度至中度食管炎。所有患者肿瘤大小均减小。4名患者有主要反应，放射学肿瘤征象几乎完全消失，5名患者部分缓解，3名患者有轻微反应。因此，总体反应率为75%。总之，尚未达到紫杉醇的最大耐受剂量，肺部感染的发生是主要临床毒性，极高的反应率值得对该方案进行进一步临床评估。
