A phase I/II trial of topotecan and radiation therapy for brain metastases in patients with solid tumors.

PURPOSE: Outcomes in patients with brain metastases undergoing whole-brain radiotherapy (WBRT) are hardly encouraging, and an improvement in results is therefore needed. One possible approach is the addition of chemotherapeutics. However the data presented thus far are also disappointing. A promising substance in this setting could become topotecan, which is known to cross the blood-brain barrier and additionally offers radiosensitizing effects. Therefore we performed a phase I/II trial to evaluate the feasibility of a concurrent radiochemotherapy regimen. METHODS AND MATERIALS: From January 1999 to July 2001, a total of 75 patients (10 in phase I and 65 in phase II) were included. The WBRT was applied with a fraction size of 2 Gy/day for a total of 40 Gy. Topotecan was administered as a 30-min infusion with 0.2 to 0.5 mg/m(2)/day for 5 days over 4 weeks within 2 h to radiation therapy. RESULTS: Because of the higher toxic rates seen in patients receiving 0.5 mg/m(2)/day, the recommended dosage for phase II was 0.4 mg/m(2)/day. In this group Grade 3/4 hematologic and nonhematologic side effects occurred in 19% and 21% of the patients, respectively. The overall response rate was 72% with an overall survival of 17 weeks and 30 weeks among the responders. CONCLUSIONS: Based on the moderate toxicity profile presented here we recommend to perform a phase III trial to confirm the promising phase I/II data.

[Atypical headache and facial pain as a result of hypertrophic pachymeningitis in C-ANCA-positive Wegener's granulomatosis]. / Atypischer Kopf- und Gesichtsschmerz infolge hypertropher Pachymeningitis bei c-ANCA positivem Morbus Wegener.

BACKGROUND: Wegener's granulomatosis (WG) is a systemic vasculitis involving the nervous system in 20-54% of cases; lesions of peripheral nerves are commonest, while manifestation in the central nervous system (CNS) is rarer. Focal hypertrophic pachymeningitis is a very rare complication of WG. This inflammatory thickening and fibrosis of the dura mater is always associated with headaches, whereas cranial nerve lesions, cerebellar symptoms or epileptic seizures occur more rarely. CASE REPORT: A 67-year-old patient, in whom WG had been diagnosed 2 years earlier and who had been treated with immunosuppressants since then, complained of continuous severe, mainly left-sided headache and facial pain for weeks. Cranial MRI showed thickening of the left tentorium cerebelli with obvious contrast enhancement and led to the diagnosis of hypertrophic pachymeningitis. The inflammatory parameters and the C-ANCA (antineutrophil cytoplasmic antibodies) in the serum were raised and CANCA were detectable in the cerebrospinal fluid. The headaches subsided with several days of intravenous high-dose corticosteroids and a simultaneous increase in the immunosuppressive basic medication. On a follow-up MRI after 3 months, the magnetic resonance changes were less apparent, i. e., the hypertrophic pachymeningitis was resolving; C-ANCA were now no longer detectable in the cerebrospinal fluid. CONCLUSION: With newly occurring, unusually severe and persistent headaches in the presence of WG, the very rare complication of hypertrophic pachymeningitis should be considered.