Oshita F, Kato Y, Yamada K, Nomura I, Sugiyama M, Yamashita K, Kitamura T, Noda K
Division of Thoracic Disease, Kanagawa Cancer Center, Asahi-ku, Yokohama 241-0815, Japan.
Oncol Rep. 1999 Mar-Apr;6(2):263-8. doi: 10.3892/or.6.2.263.
We conducted a feasibility study of continuous etoposide infusion, which was expected to suppress DNA repair after radiation, combined with radiation in patients with advanced non-small cell lung cancer (NSCLC). Between July 1995 and January 1997, 10 patients with NSCLC were registered. Thirty-six mg/m2/day etoposide was infused continuously for a mean of 19 days (range 14-26). Patients tolerated a mean total dose of accelerated hyperfractionated thoracic radiotherapy (1.5 Gy twice per day) of 52.6 Gy (range 33-60). The primary tumors of 7 patients showed partial responses and distant metastasis progression occurred before primary tumor progression in all 7 responders. The hematological adverse effects of chemoradiotherapy were grade 3 or 4 leukopenia in all 10 patients, grade 3 anemia developed in 3, and 2 had grade 3 thrombocytopenia. Six patients contracted infections and one of them died of pneumonia. The major non-hematological adverse effect was esophagitis, which was grade 3 in 3 patients, one of whom died of renal dysfunction. The serum etoposide concentrations were 1.6-2.0 microgram/ml, except in one patient, who had liver dysfunction due to B-type hepatitis. DNA repair gene XRCC1 mRNA expression in peripheral blood mononuclear cells was analyzed, using the reverse transcriptase-polymerase chain reaction, in 8 patients and was suppressed during etoposide infusion in 2. No relationship was observed between serum etoposide concentration and XRCC1 expression and clinical outcome. In conclusion, continuous etoposide infusion combined with thoracic radiation induces severe toxicity and should be given only after careful consideration.
我们对依托泊苷持续输注进行了一项可行性研究，该研究预期可抑制放疗后的DNA修复，并将其与晚期非小细胞肺癌（NSCLC）患者的放疗相结合。1995年7月至1997年1月期间，登记了10例NSCLC患者。依托泊苷以36mg/m²/天的剂量持续输注，平均持续19天（范围为14 - 26天）。患者耐受的加速超分割胸部放疗（每天两次，每次1.5Gy）的平均总剂量为52.6Gy（范围为33 - 60Gy）。7例患者的原发肿瘤出现部分缓解，且所有7例缓解者均在原发肿瘤进展前发生远处转移进展。放化疗的血液学不良反应在所有10例患者中均为3级或4级白细胞减少，3例出现3级贫血，2例出现3级血小板减少。6例患者发生感染，其中1例死于肺炎。主要的非血液学不良反应是食管炎，3例患者为3级，其中1例死于肾功能不全。除1例因乙型肝炎导致肝功能不全的患者外，血清依托泊苷浓度为1.6 - 2.0微克/毫升。使用逆转录聚合酶链反应对外周血单个核细胞中的DNA修复基因XRCC1 mRNA表达进行了分析，8例患者中有2例在依托泊苷输注期间表达受到抑制。未观察到血清依托泊苷浓度与XRCC1表达及临床结局之间的关系。总之，依托泊苷持续输注联合胸部放疗会引发严重毒性，仅应在仔细考虑后给予。
