Thema: Glioblastome mit Contergan+BCNU erfolgreich therapieren
Glioblastome mit Contergan+BCNU erfolgreich therapieren
Pascal
22.05.2001 14:06:07
Phase II Trial of Thalidomide and BCNU in Recurrent High-Grade Gliomas.
Howard Alan Fine, Elizabeth A Maher, Patrick Y Wen, Tracy Batchelor, Elene Viscosi, William Figg, National Cancer Institute, Bethesda, MD; Dana-Farber Cancer Institute, Boston, MA; Massachusetts General Hospital, Boston, MA; National Institutes of Health, Bethesda, MD.
We have previously demonstrated that thalidomide, a putative anti-angiogenic agent, has modest anti-tumor activity in recurrent high-grade gliomas. We undertook a phase II study of thalidomide in combination with BCNU to determine whether we could increase the anti-tumor effect. Patients with a histologic diagnosis of glioblastoma, anaplastic astrocytoma or mixed glioma who had radiographic demonstration of tumor progression after external beam XRT were eligible. Eighteen patients had received at least 1 prior chemotherapy regimen. Thalidomide treatment was initiated at 800 mg po qd for 2 weeks prior to treatment with BCNU (200 mg/m2 every 6 wks) and increased by 200 mg every 2 weeks to 1200 mg. Patients were evaluated every 6 weeks for clinical and radiographic response. Forty patients were enrolled, 38 GBM and 2 AA. There were 26 males and 14 females with a median age of 52 yrs. (range 26-71yrs). Thirty-nine patients were assessable for toxicity and 38 patients evaluable for response. Combination therapy was well tolerated. Grade 4 neutropenia was seen in 5 patients, grade 3 thrombocytopenia in 2 patients. Eleven patients had a DVT, complicated by PE in 6 patients. Rash resulting in cessation of therapy in 3 patients and grade 3 somnolence was seen in 3 patients. The overall response rate (CR+PR+SD) was 58%. One patient achieved a CR (3%), 4 patients achieved a PR (10%), one patient had a minimal response (3%) and 16 patients (42%) had stable disease. The median time to tumor progression was 13 weeks and median overall survival was 26 weeks. The 6 month progression free survival of the patients with recurrent GBM was 25% (9 of 36 patients). Pharmacokinetic analysis of thalidomide and BCNU will be presented. We conclude that the combination of thalidomide and BCNU was safe, well tolerated and resulted in response rates and survival time above what might have been expected with BCNU alone. When compared to our previous data using thalidomide alone in a similar group of patients, the combination of BCNU and thalidomide resulted in a higher overall response rate and improved 6 month progression free survival.
Howard Alan Fine, Elizabeth A Maher, Patrick Y Wen, Tracy Batchelor, Elene Viscosi, William Figg, National Cancer Institute, Bethesda, MD; Dana-Farber Cancer Institute, Boston, MA; Massachusetts General Hospital, Boston, MA; National Institutes of Health, Bethesda, MD.
We have previously demonstrated that thalidomide, a putative anti-angiogenic agent, has modest anti-tumor activity in recurrent high-grade gliomas. We undertook a phase II study of thalidomide in combination with BCNU to determine whether we could increase the anti-tumor effect. Patients with a histologic diagnosis of glioblastoma, anaplastic astrocytoma or mixed glioma who had radiographic demonstration of tumor progression after external beam XRT were eligible. Eighteen patients had received at least 1 prior chemotherapy regimen. Thalidomide treatment was initiated at 800 mg po qd for 2 weeks prior to treatment with BCNU (200 mg/m2 every 6 wks) and increased by 200 mg every 2 weeks to 1200 mg. Patients were evaluated every 6 weeks for clinical and radiographic response. Forty patients were enrolled, 38 GBM and 2 AA. There were 26 males and 14 females with a median age of 52 yrs. (range 26-71yrs). Thirty-nine patients were assessable for toxicity and 38 patients evaluable for response. Combination therapy was well tolerated. Grade 4 neutropenia was seen in 5 patients, grade 3 thrombocytopenia in 2 patients. Eleven patients had a DVT, complicated by PE in 6 patients. Rash resulting in cessation of therapy in 3 patients and grade 3 somnolence was seen in 3 patients. The overall response rate (CR+PR+SD) was 58%. One patient achieved a CR (3%), 4 patients achieved a PR (10%), one patient had a minimal response (3%) and 16 patients (42%) had stable disease. The median time to tumor progression was 13 weeks and median overall survival was 26 weeks. The 6 month progression free survival of the patients with recurrent GBM was 25% (9 of 36 patients). Pharmacokinetic analysis of thalidomide and BCNU will be presented. We conclude that the combination of thalidomide and BCNU was safe, well tolerated and resulted in response rates and survival time above what might have been expected with BCNU alone. When compared to our previous data using thalidomide alone in a similar group of patients, the combination of BCNU and thalidomide resulted in a higher overall response rate and improved 6 month progression free survival.
Pascal
