摘要
Background Conventional treatment for non-small cell lung cancer （NSCLC） brain metastases （BM） is whole-brain radiotherapy （WBRT）. The efficacy is limited. It might be increased by a potent radiosensitizer such as gemcitabine, which is believed to cross the disrupted blood-brain barrier. The primary objective of this study was to determine the maximum tolerated dose （MTD） of weekly gemcitabine given concurrently with WBRT. Methods Patients with BM from NSCLC were included. The dose of WBRT was 3750 cGy （total 15 times, 3 weeks）. Gemcitabine was given concurrently with WBRT on days 1, 8 and 15. The starting dose was 400 mg/m^2, escalated by 100 mg/m^2 increments. At least three patients were included per level. Dose limiting toxicity （DLT） was defined as grade 4 hematological or grade 2 neurological toxicity. When two or more patients experience DLT, the MTD was reached. Results A total of 16 patients were included; 69% had a performance status （PS） 1 （Eastern Cooperative Oncology Group, ECOG）. A total of 69% had concurrent active extra cranial diseases. All had more than 3 BM. Up to 600 mg/m^2 （level 3） no neurology toxicity was observed. At 600 mg/m^2 two out of 9 patients developed grade 4 thrombocytopenia. One of the two patients＇ thrombocytopenia was confused with disseminated intravascular coagulation （DIC）. At 700 mg/m^2 two out of 4 patients developed neurotoxicities. One developed grade 3 seizure and cognitive disorder. Another patient developed suspected grade 2 muscle weakness. Conclusions The MTD was reached at a dose of 700 mg/m^2. The dose of 600 mg/m^2 would be considered for further study.
Background Conventional treatment for non-small cell lung cancer （NSCLC） brain metastases （BM） is whole-brain radiotherapy （WBRT）. The efficacy is limited. It might be increased by a potent radiosensitizer such as gemcitabine, which is believed to cross the disrupted blood-brain barrier. The primary objective of this study was to determine the maximum tolerated dose （MTD） of weekly gemcitabine given concurrently with WBRT. Methods Patients with BM from NSCLC were included. The dose of WBRT was 3750 cGy （total 15 times, 3 weeks）. Gemcitabine was given concurrently with WBRT on days 1, 8 and 15. The starting dose was 400 mg/m^2, escalated by 100 mg/m^2 increments. At least three patients were included per level. Dose limiting toxicity （DLT） was defined as grade 4 hematological or grade 2 neurological toxicity. When two or more patients experience DLT, the MTD was reached. Results A total of 16 patients were included; 69% had a performance status （PS） 1 （Eastern Cooperative Oncology Group, ECOG）. A total of 69% had concurrent active extra cranial diseases. All had more than 3 BM. Up to 600 mg/m^2 （level 3） no neurology toxicity was observed. At 600 mg/m^2 two out of 9 patients developed grade 4 thrombocytopenia. One of the two patients＇ thrombocytopenia was confused with disseminated intravascular coagulation （DIC）. At 700 mg/m^2 two out of 4 patients developed neurotoxicities. One developed grade 3 seizure and cognitive disorder. Another patient developed suspected grade 2 muscle weakness. Conclusions The MTD was reached at a dose of 700 mg/m^2. The dose of 600 mg/m^2 would be considered for further study.
基金
This study was supported by the China Society of Clinical Oncology Foundation(No.Y-2005-0010)
