Maraveyas A, Sgouros J, Upadhyay S, Abdel-Hamid A-H, Holmes M, Lind M
Department of Academic Oncology and University of Hull, Saltshouse Road, Hull HU8 9HE, UK.
Br J Cancer. 2005 Mar 14;92(5):815-9. doi: 10.1038/sj.bjc.6602444.
Conventional treatment for brain metastases (BM) is whole-brain radiotherapy (WBRT). Efficacy is poor. It might be increased by a potent radiosensitiser such as gemcitabine which is believed to cross the disrupted blood-brain barrier. Primary objective of this study was to determine the maximum tolerated dose (MTD) of twice weekly gemcitabine given concurrently with WBRT. Patients with BM from carcinoma were included. The dose of WBRT was 30 Gys (10 daily fractions). Gemcitabine was given 2-4 h prior to WBRT on days 1 and 8 for the first cohort of patients and then on days 1, 4, 8 and 11. Starting dose was 25 mg m(-2), escalated by 12.5 mg m(-2) increments. At least three patients were included per level. Dose limiting toxicity (DLT) was defined as grade 4 haematological or grade > or =3 nonhaematological toxicity. A total of 25 patients were included; 74% had a PS 1 (ECOG). In all, 23 had non-small-cell lung cancer, six colorectal, four breast, two renal cell and one oesophageal carcinoma. A total of 92% had concurrent extracranial disease. Six had single BM, 13 had two or three BM and six multiple. Up to 50 mg m(-2) (level 4) no DLT was observed. At 62.5 mg m(-2), one out of six patients developed DLT (thrombocytopenia-bleeding). The next dose level (75 mg m(-2)) was abandoned after grade 4 bone marrow toxicity (fatal neutropenic sepsis) was seen in one out of two patients. So that the dose of 50 mg m(-2) will be taken forward for further study.
脑转移瘤（BM）的传统治疗方法是全脑放疗（WBRT）。其疗效较差。使用如吉西他滨这样的强效放射增敏剂可能会提高疗效，据信吉西他滨能够穿过被破坏的血脑屏障。本研究的主要目的是确定与WBRT同时使用的每周两次吉西他滨的最大耐受剂量（MTD）。纳入了患有癌性脑转移瘤的患者。WBRT的剂量为30 Gy（每日10次分割）。对于第一组患者，在第1天和第8天的WBRT前2 - 4小时给予吉西他滨，随后在第1、4、8和11天给药。起始剂量为25 mg/m²，以12.5 mg/m²的增量递增。每个剂量水平至少纳入3名患者。剂量限制毒性（DLT）定义为4级血液学毒性或≥3级非血液学毒性。总共纳入了25名患者；74%的患者体力状况评分为1（东部肿瘤协作组）。其中，23例为非小细胞肺癌，6例为结直肠癌，4例为乳腺癌，2例为肾细胞癌，1例为食管癌。总共92%的患者同时患有颅外疾病。6例为单发脑转移瘤，13例为2 - 3个脑转移瘤，6例为多发脑转移瘤。在高达50 mg/m²（第4级水平）时未观察到DLT。在62.5 mg/m²时，6例患者中有1例出现DLT（血小板减少伴出血）。在2例患者中有1例出现4级骨髓毒性（致命性中性粒细胞减少性败血症）后，放弃了下一个剂量水平（75 mg/m²）。因此，50 mg/m²的剂量将用于进一步研究。
