Triple-drug Therapy With Bevacizumab, Irinotecan, and Temozolomide Plus Tumor Treating Fields for Recurrent Glioblastoma: A Retrospective Study

Abstract

Clinical studies treating pediatric and adult solid tumors, such as glioblastoma (GBM), with a triple-drug regimen of temozolomide (TMZ), bevacizumab (BEV), and irinotecan (IRI) [TBI] have demonstrated various efficacies, but with no unexpected toxicities. The TBI regimen has never been studied in recurrent GBM (rGBM) patients. In this retrospective study, we investigated the outcomes and side effects of rGBM patients who had received the TBI regimen. We identified 48 adult rGBM patients with a median age of 56 years (range: 26–76), who received Tumor Treating Fields (TTFields) treatment for 30 days or longer, and concurrent salvage chemotherapies. The patients were classified into two groups based on chemotherapies received: TBI with TTFields (TBI+T, N = 18) vs. bevacizumab (BEV)-based chemotherapies with TTFields (BBC+T, N = 30). BBC regimens were either BEV monotherapy, BEV+IRI or BEV+CCNU. Patients in TBI+T group received on average 19 cycles of TMZ, 26 and 21 times infusions with BEV and IRI, respectively. Median overall survival (OS) and progression-free survival (PFS) for rGBM (OS-R and PFS-R) patients who received TBI+T were 18.9 and 10.7 months, respectively. In comparison, patients who received BBC+T treatment had OS-R and PFS-R of 11.8 (P > 0.05) and 4.7 (P < 0.05) months, respectively. Although the median PFS results were significantly different by 1.5 months (6.6 vs. 5.1) between TBI+T and BBC+T groups, the median OS difference of 14.7 months (32.5 vs. 17.8) was more pronounced, P < 0.05. Patients tolerated TBI+T or BBC+T treatments well and there were no unexpected toxicities. The most common side effects from TBI+T treatment included grade III hypertension (38.9%) and leukopenia (22.2%). In conclusion, the TBI regimen might play a role in the improvement of PFS-R and OS-R among rGBM patients. Prospective studies with a larger sample size are warranted to study the efficacy and toxicity of TBI+T regimen for rGBM.

Tumor treating fields cause replication stress and interfere with DNA replication fork maintenance: Implications for cancer therapy

“…However, the results herein could be considered as an explanation for clinical trial results where replication stress inducing agents were combined with TTFields. 70,72 Finally, TTFields are now applied either alone, postsurgery and/or radiation, and often concomitantly with chemotherapy agents. The data herein suggest that other therapeutic strategies should be considered so as to take advantage of the vulnerabilities generated by prior or concomitant TTFields exposure.…”

The Value of Tumor Treating Fields in Glioblastoma

“…It can be seen that the treatment plan has great potential for GBM patients. Hypertension (38.9%) were the most common side effects without unexpected severe toxicities in this study 18) .…”

“…Another retrospective study showed that the OS and PFS of 18 GBM patients receiving TMZ, BEV, and irinotecan in combination with TTFields were 18.9 and 10.7 months, respectively 18) . It can be seen that the treatment plan has great potential for GBM patients.…”

Identification of potential biomarkers and candidate small molecule drugs in glioblastoma

“…Previous study indicated that genes such as estrogen receptor 2 (ESR2), ELOVL fatty acid elongase 6 (ELOVL6), iroquois homeobox 3 (IRX3), PDZ binding kinase (PBK), centromere protein A (CENPA), and kinesin family member 15 (KIF15) were signi cantly associated with the prognosis of GBM, suggesting that these genes might be potential targets for GBM treatment [4,5]. Additionally, drugs like triple-drug therapy (bevacizumab, irinotecan, and temozolomide) had bene t effect on recurrent GBM [6]. However, different studies often yield diverse results and the molecular mechanism of GBM pathogenesis has not been entirely elucidated.…”