Tailored chemotherapy of malignant gliomas

Introduction: We developed a concept of an individualized multi-drug-chemotherapy on the basis of in-vitro-testing with the mirotiter-tetrazolium-assay (MTT-assay) to improve the grim prognosis of patients with malignant gliomas. Methods: 77 out of 110 consecutive patients with a malignant glioma WHO III and IV were tested by means of the MTT-assay for 8 different chemotherapeutic agents. In the clinical protocol, the full chemotherapy schedule consisted of twelve cycles in one year. Every 4 months or in cases of a suspected tumor progression, CT, MRI, as well as IMT-SPECTR to monitor for biological activity performed. Results: 21 out of 77 tested cell cultures (24%) were resistant against all cytotoxic agents. 75 out of 77 (97%) showed primary chemoresistance against ACNU. The remaining cell cultures showed an individual response pattern against several chemotherapeutic agents. 23 patients agreed to the postoperative protocol. In spite of the positive response in-vitro, 14 patients (60%) showed tumor progression during chemotherapy. Six patients (26%) showed partial remission after 2 to 10 cycles. The remaining three patients have already finished the complete therapy cycle. All have a proven complete tumor remission without any signs of a new tumor progression 17, 27 respectively 40 months after surgery. Discussion and conclusions: The ongoing clinical trials using mono-chemotherapy, particularly using ACNU, should be critically revised. Amongst the heterogenous group of malignant gliomas, there is a group with a clear clinical benefit from adjuvant chemotherapy. After identification of in-vitro chemosensitivity, the chance for complete remission or at least partial remission seems to be 40%.