Graham M V, Jahanzeb M, Dresler C M, Cooper J D, Emami B, Mortimer J E
Radiation Oncology Center, Washington University Medical School, St. Louis, MO 63110, USA.
Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):1215-20. doi: 10.1016/s0360-3016(96)00367-7.
To conduct a dose escalation clinical study with topotecan and concurrent standard dose thoracic irradiation to assess its feasibility and toxicity in the treatment of patients with locally advanced, inoperable nonsmall cell lung cancer (NSCLCA).
Between April 1993 and August 1994, 12 patients with inoperable, loco-regionally advanced NSCLCA were entered in a prospective dose escalation trial and assigned to receive concurrent thoracic radiotherapy and topotecan. Patients received thoracic irradiation to a total tumor dose of 60 Gy in 30 fractions. Initial fields were to encompass the gross disease plus the mediastinum. Topotecan was delivered by bolus injection days 1 through 5, and days 22 through 26, beginning on the same day as the radiation therapy. The initial dose level was 0.5 mg/m2. Two additional dose levels of 0.75 mg/m2 and 1.0 mg/m2 were tested.
Six patients were accessioned to the 0.5 mg/m2 dose level, three patients to the 0.75 mg/m2 dose level, and three patients to the 1.0 mg/m2 dose level. At the 0.5 mg/m2 dose level, zero of six patients had > or = Grade 4 hematologic toxicity. One of the six had Grade 3 esophagitis. At the 0.75 mg/m2 dose level, two of three patients had > or = Grade 3 nonhematologic toxicity including anorexia, fatigue, nausea, vomiting, and weakness; zero patients experienced > or = Grade 4 hematologic toxicity. At the 1.0 mg/m2 dose level one of three patients had > or = Grade 3 esophagitis, and two of three patients experienced Grade 4 neutropenia. With a follow-up of 12 to 24 months, two patients are alive and free of disease, three patients are alive with disease (two with distant metastasis, one with local disease and distant metastasis), and the remaining seven patients are dead of disease.
The combination of topotecan and thoracic radiotherapy for nonsmall lung cancer, in the manner given by this protocol, could be safely given at a dose level of only 0.5 mg/m2 days 1 to 5 and 22 to 26 with 60 Gy of external beam radiotherapy. Higher doses of topotecan were associated with high hematologic and gastrointestinal toxicity. Distant metastasis was the primary pattern of failure.
开展一项拓扑替康与标准剂量同期胸部放疗的剂量递增临床研究，以评估其治疗局部晚期、无法手术切除的非小细胞肺癌（NSCLCA）患者的可行性和毒性。
1993年4月至1994年8月期间，12例无法手术切除、局部区域晚期的NSCLCA患者进入一项前瞻性剂量递增试验，被分配接受同期胸部放疗和拓扑替康治疗。患者接受胸部放疗，总肿瘤剂量60 Gy，分30次给予。初始野包括大体肿瘤及纵隔。拓扑替康在放疗开始当天第1至5天及第22至26天通过静脉推注给药。初始剂量水平为0.5 mg/m²。另外测试了0.75 mg/m²和1.0 mg/m²两个剂量水平。
6例患者进入0.5 mg/m²剂量水平组，3例患者进入0.75 mg/m²剂量水平组，3例患者进入1.0 mg/m²剂量水平组。在0.5 mg/m²剂量水平组，6例患者中无1例出现≥4级血液学毒性。6例中有1例出现3级食管炎。在0.75 mg/m²剂量水平组，3例患者中有2例出现≥3级非血液学毒性，包括厌食、疲劳、恶心、呕吐和虚弱；无患者出现≥4级血液学毒性。在1.0 mg/m²剂量水平组，3例患者中有1例出现≥3级食管炎，3例中有2例出现4级中性粒细胞减少。随访12至24个月，2例患者存活且无疾病，3例患者存活但有疾病（2例有远处转移，1例有局部疾病和远处转移），其余7例患者死于疾病。
按照本方案给予拓扑替康与胸部放疗联合治疗非小细胞肺癌，在仅0.5 mg/m²第1至5天及第22至26天并联合60 Gy外照射放疗的剂量水平下可安全给药。更高剂量的拓扑替康与高血液学和胃肠道毒性相关。远处转移是主要的失败模式。
