Skip to main content
Article thumbnail
Location of Repository

Gemcitabine twice weekly as a radiosensitiser for the treatment of brain metastases in patients with carcinoma: a phase I study

By A Maraveyas, J Sgouros, S Upadhyay, A-H Abdel-Hamid, M Holmes and M Lind


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 ⩾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

Topics: Clinical Studies
Publisher: Nature Publishing Group
OAI identifier:
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    1. (1992). Difluorodeoxycytidine (dFdC)-gemcitabine: a phase I study.
    2. (2005). Oncol 20: 804–810 Van den Bent MJ (2003) The role of chemotherapy in brain metastases.
    3. (1999). Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer.
    4. (2001). Radiation concurrent with gemcitabine for locally advanced head and neck cancer: a phase I study and intracellular drug incorporation study. J Clin Oncol 19: 792–799 Folstein MF, Folstein SE, McHugh PR
    5. (2001). Recent advances in the use of radiosensitizing nucleosides. Semin Radiat Oncol 11: 270–280

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.