Chemotherapy in malignant brain tumors

Transcription

1 Chemotherapy in malignant brain tumors Frank Zimmermann Institut für Radioonkologie Universitätsspital Basel Petersgraben 4 CH 4031 Basel zimmermannf@uhbs.ch

2 Tumor types Neuro-epithelial tumors - Glioblastoma - Astrocytoma Oligodendroglioma Ependymal tumors Embryonal tumors - Medulloepithelioma - Neuroblastoma - Medulloblastoma Meningeoma a.o.

3 Neuroepithelial tumors

4 Temozolomide-based trial Overall median survival (16 months, n.s.) and quality of life (s.) (German trial: 65 pts., 11 centers) Kocher et al. Strahlenther Onkol 2008

5 Glioblastoma Overall median survival (14.6 vs months, s.) > CHF more than RT alone (s.) CHF more per gained year (European and Canadian trial: 573 pts., 85 centers) Stupp et al. N Engl J Med 2005 Lamers et al. Cancer 2008

6 Temozolomide-based treatment Overall median survival (13.4 vs. 7.7 months, s.) (Greek trial: 110/130 pts., in 36 months, 5 centers) Athanassiou et al. J Clin Oncol 2005

7 Temozolamide treatment Wolf et al. J Neurooncol 2008

8 MGMT - Resistance to alkylating agents O 6 -methylguanine methyltransferase (MGMT) is a cellular DNA repair protein that rapidly reverses alkylation (including methylation) at the O 6 position of guanine, thereby neutralizing the cytotoxic effects of alkylating agents such as temozolomide or nitrosoureas. Guanine Gerson et al., J Clin Oncol 2002 Hegi et al. J Clin Oncol 2008

9 MGMT - Resistance to alkylating agents Methylation of the MGMT promoter has been observed in a variety of tumor types and results in a decreased MGMT expression in tumor cells thus leading to reduced resistance to alkylating agents. At present not used to exclude initiation of chemotherapy! acc. to Hegi et al. J Clin Oncol 2008

10 MGMT-Methylation and outcome Hegi et al. J Clin Oncol 2008

11 ACNU-based treatment Overall median survival (17.3 vs months, n.s.) 3000 CHF more than RT alone (s.) (German trial: 375 pts., 16 centers) Weller et al. J Clin Oncol 2003

12 Nitrosoureas-based treatment Based on patients Wolf et al. J Neurooncol 2008

13 Neuro-epithelial tumors NOA-1 EORTC Pats. 362 / / 573 Glioblastoma 83.1 % 92.5 % Median OS in Glioblastoma Toxicity > II Conclusion 17.3 / 15.7 months 14.6 / 12.1 months 20 % leukopenia 13 % thrombopenia 2 % anemia RT + ACNU + VM26 (teniposide) 14 % leukopenia 12 % thrombopenia 1 % anemia RT + Temozolomide

14 Concepts and costs Concepts in Glioblastoma in Astrocytoma? Temozolomide: 5 x 75 mg/sqm weekly during RT 5 x mg/sqm weekly every 4 weeks for 6 cycles (30.000,00 CHF) ACNU / tenoposide: 1 x 90 mg/qm and 3 x 60 mg/sqm every 6 weeks (3.000,00 CHF) Anti-angiogenesis (bevacizumab, sorafinib) in studies (in recurrent tumors)

15 Oligodendroglioma and -astrocytoma Treatment with PCV (procarbazine, lomustine, vincristin) Progression-free survival (23.0 vs months, s) 65 % toxicity III-IV Van den Bent et al. J Clin Oncol 2006

16 Systemic treatment Treatment with PCV (procarbazine, lomustine, vincristin) or temozolamide (response rate about 75 %) Taliansky-Aronov et al. J Neurooncol 2006 Mohile et al. J Neurooncol 2008

17 Brain metastases Concepts Small cell lung cancer: Response rates % chemotherapy when no neurol. symptoms Breast cancer: Response rates % Non-small cell lung cancer: Response rates % No survival benefit for simultaneous application of radioand chemotherapy (topotecan? targeted therapies?) Soffietti et al. Curr Opin Oncol 2008

18 Conclusion Chemotherapy in glioblastoma is an individual decision driven by There is not 1 standard Chemotherapy in astrocytoma and oligodendroglioma is open In low-grade gliomas chemotherapy should not be offered Children should be treated within protocols only