Center of Radiation-Oncology, Gröpelinger Heerstr. 406-408, 28239 Bremen, Germany.
J Cancer Res Clin Oncol. 2012 Jul;138(7):1113-20. doi: 10.1007/s00432-012-1185-3. Epub 2012 Mar 10.
Fludarabine is an adenine nucleoside analogue that has significant activity in hematological malignancies and has shown promising activity in combination with radiation in preclinical solid tumor models. We designed a phase I trial exploring concurrent fludarabine and radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) to determine the maximum tolerated dose (MTD) of fludarabine given with concurrent irradiation.
Thirteen patients with stage IIIB NSCLC received thoracic irradiation of 60 Gy. Fludarabine was administered during the 5th and 6th week of radiotherapy. Doses started at 10 mg/m(2) per day and increased by steps of 3 mg/m(2) per day.
At a daily dose of 16 mg/m(2), one out of six patients developed a grade 4 leukopenia, and one a grad 3 pneumonitis. Further grade III toxicity was not observed. The dose of 13 mg/m(2) was identified as the MTD. All patients developed a fludarabine dose-dependent lymphocytopenia.
Fludarabine can be safely administered concurrently with radiation at a daily dose of 13 mg/m(2) during the final 2 weeks of radiotherapy. Further prospective clinical studies are required to establish the potential role of concurrent fludarabine and radiotherapy in the treatment of locally advanced inoperable NSCLC.
氟达拉滨是一种腺嘌呤核苷类似物，在血液系统恶性肿瘤中有显著的活性，并在临床前实体瘤模型中与放射治疗联合显示出有前途的活性。我们设计了一项Ⅰ期临床试验，旨在探索氟达拉滨与放疗联合用于晚期非小细胞肺癌（NSCLC）患者，以确定氟达拉滨与同期放疗联合应用的最大耐受剂量（MTD）。
13 例ⅢB 期 NSCLC 患者接受 60 Gy 的胸部放疗。氟达拉滨在放疗的第 5 周和第 6 周给予。剂量从每天 10mg/m2开始，每天增加 3mg/m2。
在每天 16mg/m2的剂量下，6 例患者中有 1 例出现 4 级白细胞减少症，1 例出现 3 级肺炎。未观察到进一步的 3 级毒性。确定 13mg/m2为 MTD。所有患者均出现氟达拉滨剂量依赖性淋巴细胞减少症。
氟达拉滨可以在放疗的最后 2 周内，每天 13mg/m2的剂量与放疗安全联合应用。需要进一步的前瞻性临床研究来确定氟达拉滨与放疗同期治疗局部晚期不可手术 NSCLC 的潜在作用。
