The prognosis of patients with brain metastases is very poor. In this phase I/II study we tested the feasibility, dosage, toxicity and tumour efficacy of a concurrent radiochemotherapy regimen including topotecan. Twenty patients were recruited between July 1998 and February 2000 (9 women, 11 men) and treated with a whole-brain irradiation of 40 Gy (some patients were also given a boost) in combination with topotecan given as a 21-day continuous infusion in a dosage of 0.4 to 0.6 mg/m2/day. The median survival was five months (95% Confidence Interval (CI): 2-8 months). In 13 of 20 patients, it was possible to evaluate the remission with computed tomography (CT) scans or magnetic resonance scans. We detected four complete responders (CRs), two partial responders (PRs), and one progressive disease (PD). 6 patients had stable disease (SD). An intracerebral recurrence was experienced in 3 patients, 3 patients experienced spinal lesions. Systemic progression of cancer outside the central nervous system (CNS) was dominant in 9 of 20 patients. A reversible, non-cumulative haematological toxicity mainly occurring from a dose of 0.5 mg/m2/day and above was dose-limiting for this type of therapy. Combined concurrent radiochemotherapy with topotecan is feasible in spite of various pretreatments. Myelosuppression was the dominant toxicity, which was reversible and manageable. We recommend a dose of 0.4 mg/m2/day of topotecan as a 21-day continuous infusion therapy in combination with radiotherapy.