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.
Authors: Yaacov Richard Lawrence; Bhadrasain Vikram; James J Dignam; Arnab Chakravarti; Mitchell Machtay; Boris Freidlin; Naoko Takebe; Walter J Curran; Soren M Bentzen; Paul Okunieff; C Norman Coleman; Adam P Dicker Journal: J Natl Cancer Inst Date: 2012-12-10 Impact factor: 13.506
Authors: Maikel Verduin; Jaap D Zindler; Hanneke M A Martinussen; Rob L H Jansen; Sander Croes; Lizza E L Hendriks; Danielle B P Eekers; Ann Hoeben Journal: Oncologist Date: 2017-02-06