Molecularly Targeted Drugs Plus Radiotherapy and Temozolomide Treatment for Newly Diagnosed Glioblastoma: A Meta-Analysis and Systematic Review

Abstract

Glioblastoma (GBM) is the most common primary malignant brain tumor that nearly always results in a bad prognosis. Temozolomide plus radiotherapy (TEM+RAD) is the most common treatment for newly diagnosed GBM. With the development of molecularly targeted drugs, several clinical trials were reported; however, the efficacy of the treatment remains controversial. So we attempted to measure the dose of the molecularly targeted drug that could improve the prognosis of those patients. The appropriate electronic databases (PubMed, MEDLINE, EMBASE, and the Cochrane Library) were searched for relevant studies. A meta-analysis was performed after determining which studies met the inclusion criteria. Six randomized, controlled trials (RCTs) were identified for this meta-analysis, comprising 2,637 GBM patients. The benefit of overall survival (OS) was hazard ratio (HZ), 0.936 [95% confidence interval (CI), 0.852-1.028]. The benefit with respect to progression-free survival (PFS) rate was HZ of 0.796 (95% CI, 0.701-0.903). OS benefit of cilengitide was HZ of 0.792 (95% CI, 0.642-0.977). The adverse effects higher than grade 3 were 57.7% in the experimental group and 44.1% in the placebo group (odds ratio, 1.679; 95% CI, 1.434-1.967). The addition of molecularly targeted drugs to TEM + RAD did not improve the OS of patients with GBM; however, it did improve PFS in patients treated by cilengitide who could not get improvement in OS. The rate of adverse effects was higher in the experimental group than in the placebo group.

Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43‑mediated gap junction intercellular communication

“…The typical therapies for GBM involves surgery, chemotherapy, radiotherapy or combination therapy. TMZ is a front-line chemo-alkylating agent used to treat glioblastoma (16). TMZ causes DNA damage through the DNA alkylation, which induces mismatches in the DNA repair pathway and finally leads to cell death.…”

Targeting Angiogenesis in Prostate Cancer

“…The direct anti-angiogenic effect of targeting integrins (cellular adhesion receptors), has also been demonstrated [32]; an integrin inhibitor—cilentigide—has been shown to inhibit tumor cell invasion [33]. Unfortunately, even though cilentigide acts both on tumor cells and endothelial cells and could be a prime example of multifactorial treatment, results of clinical trials have proved disappointing so far [34].…”

Comparative effect of immunotherapy and standard therapy in patients with high grade glioma: a meta-analysis of published clinical trials

“…While some treatment protocols such as bevacizumab alongside irinotecan have been established as being viable salvage options for the treatment of recurrent GBM, no new treatments for newly diagnosed tumors have been included into standard practice. However, a few recent meta-analysis and systematic reviews on targeted treatment for newly diagnosed GBM have indicated that combination between standard of care treatment and targeted agents could prove superior to standard of care treatments alone 35 , 36 . Both these studies present major limitations and the data presented is not sufficient for the combinations to be considered as strong candidates for inclusion into mainstay protocols.…”