Aim: To determine whether or not brain radiotherapy and concomitant three-drug chemotherapy is feasible and yields anti-tumour activity in patients with non-small cell lung cancer and brain metastases at time of presentation. Patients and methods: Twenty-three previously untreated patients suffering from non-small cell lung cancer and brain metastasis were prospectively included in this feasibility study. Most of the patients had neurological symptoms and an Eastern Collaborative Oncology Group (ECOG) performance index over 2. Treatment consisted of three courses of whole brain radiotherapy (18 Gy in 10 fractions) and vinorelbine, 30 mg/m(2) on days 1 and 8, ifosfamide, 1.5 g/m(2) daily from day 1 through day 3 with uromitexan uroprotection, and cisplatin, 100 mg/m(2) on day 2. A cycle restarted every 28 days. Results: Eighteen patients completed the three-cycle programme. All patients were affected by a grade 4 neutropenia and 14 of them experienced a febrile episode. Other toxicities were mild to moderate and manageable. Received-dose intensities of vinorelbine, ifosfamide and cisplatin were 80, 90 and 90%, respectively. Overall response rate was 30%. Specific evaluation of brain response demonstrated complete response for seven patients, and partial response in six (objective brain response rate, 56%). All responders benefited by a remission of symptoms and improvement of performance index. Median survival from start of protocol was 7.6 months. Conclusion: Although the high rate of toxicity requiring re-admission, concomitant brain radiotherapy plus vinorelbine, ifosfamide and cisplatin chemotherapy is feasible in patients suffering from brain metastasis, and demonstrates an anti-tumour activity for this particular subset of stage IV non-small cell lung cancer. The development of such an aggressive approach needs further comparative evaluation. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
