title: Gemcitabine twice weekly as a radiosensitiser for the treatment of brain metastases in patients with carcinoma: a phase I study.
abstract: 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.
authors.affiliation: Department of Academic Oncology and University of Hull, Saltshouse Road, Hull HU8 9HE, UK. A.Maraveyas@hull.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Maraveyas
authors.forename: J
authors.initials: J
authors.lastname: Sgouros
authors.forename: S
authors.initials: S
authors.lastname: Upadhyay
authors.forename: A-H
authors.initials: AH
authors.lastname: Abdel-Hamid
authors.forename: M
authors.initials: M
authors.lastname: Holmes
authors.forename: M
authors.initials: M
authors.lastname: Lind
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000556:secondary*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D012074:Remission Induction / Q000379:methods; D000093542:Gemcitabine
chemical_list: D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine