Temozolomide and Radiotherapy versus Radiotherapy Alone in High Grade Gliomas: A Very Long Term Comparative Study and Literature Review

Abstract

Temozolomide (TMZ) is the first line drug in the care of high grade gliomas. The combined treatment of TMZ plus radiotherapy is more effective in the care of brain gliomas then radiotherapy alone. Aim of this report is a survival comparison, on a long time (>10 years) span, of glioma patients treated with radiotherapy alone and with radiotherapy + TMZ. Materials and Methods. In this report we retrospectively reviewed the outcome of 128 consecutive pts with diagnosis of high grade gliomas referred to our institutions from April 1994 to November 2001. The first 64 pts were treated with RT alone and the other 64 with a combination of RT and adjuvant or concomitant TMZ. Results. Grade 3 (G3) haematological toxicity was recorded in 6 (9%) of 64 pts treated with RT and TMZ. No G4 haematological toxicity was observed. Age, histology, and administration of TMZ were statistically significant prognostic factors associated with 2 years overall survival (OS). PFS was for GBM 9 months, for AA 11. Conclusions. The combination of RT and TMZ improves long term survival in glioma patients. Our results confirm the superiority of the combination on a long time basis.

GADD45A plays a protective role against temozolomide treatment in glioblastoma cells

“…Therefore, it is essential to develop more effective therapeutic regimens for GBM treatment. To identify novel targets to improve the current chemotherapeutic regimens, we performed expression profiling of chemo-sensitive (U87) and resistant (T98) GBM cell lines treated with TMZ, the first-line treatment for GBM 19 . Among the fourteen genes found to be substantially regulated in TMZ-treated U87 cells, GADD45A was identified in both the cell cycle and apoptosis arrays.…”

The Side Effects of Chemotherapy in Glioma

“…The previous study revealed that TMZ administration combined with radiotherapy has good efficacy for a patient with glioblastoma multiforme. 5…”

“…During DNA replication, methylated guanine will couple with thymidine (which should be coupled with cytidine) thus cause mismatch repair and induce apoptosis. 5,7 These cellular repair mechanisms are dysfunctional and lead to apoptosis. 8 Bioavailability of oral TMZ is 100% and possesses good penetration through blood-brain barrier as well as brain tumor tissue.…”

“…3,4 The role of chemotherapy as an essential step for management of glioma in the context of scientific development in last several years was increased because of two reasons: sensitivity of 1p/19q on oligodendroglioma toward chemotherapy and availability of temozolomide, novel alkylating agents which has good penetration on the central nervous system. 5 Relatively significant differences on the survival rate of a patient with glioblastoma multiforme after diagnosis were correlated with administration of chemotherapeutic agent Temodar (temozolomide) that could increase average survival rate in combined treatment (radiation therapy and chemotherapy) for 2.5 months compared to radiation therapy alone (14,6 months vs. 12,1 months, respectively). Furthermore, at the end of the second year, the survival rate in the radiotherapi+chemotherapy group was higher as compared to radiotherapy alone (26,5% vs. 10,4%, respectively).…”

Hippocampal sparing in brain radiotherapy

“…It should however be stressed that using combination therapy in patients with brain tumours increases the chances of an ever longer survival. An example is afforded by patients suffering from glioblastoma multiforme (glioblastoma), where the combination of surgical treatment with adjuvant chemoradiotherapy improves local control (LC) and extends overall survival (OS) [2]. At the same time, patients undergoing antineoplastic therapy are more likely to suffer from worsening psychomotor dysfunction.…”