Gagel Bernd, Piroth Marc, Pinkawa Michael, Reinartz Patrick, Krohn Thomas, Kaiser Hans J, Stanzel Sven, Breuer Christian, Asadpour Branka, Schmachtenberg Axel, Eble Michael J
Department of Radiotherapy, RWTH Aachen University, Germany.
BMC Cancer. 2007 Jun 28;7:112. doi: 10.1186/1471-2407-7-112.
The aim of the study was to determine the maximal tolerated dose (MTD) of gemcitabine every two weeks concurrent to radiotherapy, administered during an aggressive program of sequential and simultaneous radiochemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC) and to evaluate the efficacy of this regime in a phase II study.
33 patients with histologically confirmed NSCLC were enrolled in a combined radiochemotherapy protocol. 29 patients were assessable for evaluation of toxicity and tumor response. Treatment included two cycles of induction chemotherapy with gemcitabine (1200 mg/m2) and vinorelbine (30 mg/m2) at day 1, 8 and 22, 29 followed by concurrent radiotherapy (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every two weeks at day 43, 57 and 71. Radiotherapy planning included [18F] fluorodeoxyglucose positron emission tomography (FDG PET) based target volume definition. 10 patients were included in the phase I study with an initial gemcitabine dose of 300 mg/m2. The dose of gemcitabine was increased in steps of 100 mg/m2 until the MTD was realized.
MTD was defined for the patient group receiving gemcitabine 500 mg/m2 due to grade 2 (next to grade 3) esophagitis in all patients resulting in a mean body weight loss of 5 kg (SD = 1.4 kg), representing 8% of the initial weight. These patients showed persisting dysphagia 3 to 4 weeks after completing radiotherapy. In accordance with expected complications as esophagitis, dysphagia and odynophagia, we defined the MTD at this dose level, although no dose limiting toxicity (DLT) grade 3 was reached. In the phase I/II median follow-up was 15.7 months (4.1 to 42.6 months). The overall response rate after completion of therapy was 64%. The median overall survival was 19.9 (95% CI: [10.1; 29.7]) months for all eligible patients. The median disease-free survival for all patients was 8.7 (95% CI: [2.7; 14.6]) months.
After induction chemotherapy, the maximum tolerated dose and frequency of gemcitabine was defined at 500 mg/m2 every two weeks in three cycles during a maximum of 7 weeks of thoracic radiotherapy for the phase II study. This regimen represents an effective and tolerable therapy in the treatment of NSCLC.
本研究的目的是确定在局部晚期、不可切除的非小细胞肺癌（NSCLC）的序贯和同步放化疗积极方案中，每两周一次与放疗同步使用的吉西他滨的最大耐受剂量（MTD），并在一项II期研究中评估该方案的疗效。
33例经组织学确诊的NSCLC患者纳入联合放化疗方案。29例患者可评估毒性和肿瘤反应。治疗包括在第1、8、22和29天进行两个周期的诱导化疗，使用吉西他滨（1200 mg/m²）和长春瑞滨（30 mg/m²），随后进行同步放疗（2.0 Gy/天；总剂量66.0 Gy），并在第43、57和71天每两周使用吉西他滨进行化疗。放疗计划包括基于[18F]氟脱氧葡萄糖正电子发射断层扫描（FDG PET）的靶区定义。10例患者纳入I期研究，初始吉西他滨剂量为300 mg/m²。吉西他滨剂量以100 mg/m²的步长增加，直至达到MTD。
接受吉西他滨500 mg/m²的患者组确定了MTD，因为所有患者均出现2级（仅次于3级）食管炎，导致平均体重减轻5 kg（标准差 = 1.4 kg），占初始体重的8%。这些患者在完成放疗后3至4周仍有吞咽困难。按照食管炎、吞咽困难和吞咽痛等预期并发症，我们在该剂量水平确定了MTD，尽管未达到3级剂量限制毒性（DLT）。在I/II期，中位随访时间为15.7个月（4.1至42.6个月）。治疗完成后的总体缓解率为64%。所有符合条件患者的中位总生存期为19.9（95%CI：[10.1；29.7]）个月。所有患者的中位无病生存期为8.7（95%CI：[2.7；14.6]）个月。
在II期研究中，诱导化疗后，吉西他滨的最大耐受剂量和频率确定为每两周500 mg/m²，共三个周期，在最多7周的胸部放疗期间使用。该方案是治疗NSCLC的一种有效且可耐受的疗法。
