Weekly gemcitabine as a radiosensitiser for the treatment of brain metastases in patients with non-small cell lung cancer: phase I trial.
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.
Huang
Yu-juan
YJ
Department of Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangzhou 510080, China.
Wu
Yi-long
YL
Xie
Song-xi
SX
Yang
Jing-ji
JJ
Huang
Yi-sheng
YS
Liao
Ri-qiang
RQ
D000368:Aged; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D016371:Cranial Irradiation; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D000093542:Gemcitabine
D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine