Phase Ii Trial Of Bevacizumab, Irinotecan, And Cetuximab In Recurrent Glioblastoma Multiforme: Efficacy, Safety And Clinical Outcomes

Abstract

The glioblastoma multiforme (GBM) is an aggressive and lethal to some extent of the most primary brain cancer that is not so responsive to conventional therapy and with a median survival time of approximately 15 months on patients with diagnosed cases of GBM. Things are even worse when it comes to the situation with the recurrent GBM when survival rates are in the range of 3 to 9 months despite conventional chemotherapy. Some piecemeal combination of angiogenesis and EGFR has shown some hint of therapeutic promise in preclinical and early clinical experiments. It is a phase II trial which is to verify the safety and the efficacy of a three drugs combination- bevacizumab (anti-VEGF), irinotecan (topoisomerase I inhibitor) and cetuximab (anti-EGFR monoclonal antibody) in patients who have recurrent primary GBM. Big patients: one hundred adults of recurrent primary GBM that was histologically confirmed were recruited. One needed to be eligible and have radiologically documented relapse of the disease within the first six months of the regular chemoradiotherapy using temozolomide. They received bevacizumab (5-10 mg / kg on alternate weeks), dose-adjusted irinotecan (depending upon antiepileptic use), and cetuximab (400 mg / m 2 if loading dose and 250 mg / m 2 as a continuing dose on a weekly basis.). The main outcome measure is the objective response rate (ORR), whereas progression-free survival (PFS), disease control rate (DCR), and safety were the secondary outcome measures. The population involved was males: 58 per cent having a median age of 54 years. The performance status according to the WHO (0-2) was exhibited in all the patients. The ORR was 26 percent of which 5 and 21 percent are complete response (CR) and partial response (PR), respectively. The DCR was 66 percent with the patients maintaining stable disease (SD) on a 40 percent basis. The proportions who experienced disease progression were 9 percent and those not analyzable was 25 percent as they could not complete it as they dropped off prematurely. Median PFS was 16 and 6-month PFS was 33 percent. At 6 months PFS was 73 percent in responders (CR or PR). The treatment process as a whole was not difficult; the dose reductions as well as the termination of the treatment occurred according to the determined pre-decided criteria of toxicity. The given study is the first phase II study which examines the combination therapy usage of cetuximab-bevacizumab-irinotecan, in the recurrent GBM. Quantifiable antitumor activity and clinical significance was lawful in a small subset of patients, as shown by the recorded ORR and DCR. Overexpression of EGFR was identified in 27 percent of total number of patients who could be assessable though the presence of an identifiable trend was not identified as far as the response to the treatment was concerned. An evidence-based line of argument must be VEGF-EGFR-mediated path across-the-board owing and the said effect is fairly safe with promising benefit in regard to efficacy and, subsequently, requires being researched in greater trails. The essence of an intervention of bevacizumab, irinotecan and cetuximab, as treatment approach of recurrent GBM, proves to have a great potential with a fair toxicity profile and a 66 percent disease control rate. There is a necessary need to do more research to determine the superior way of patient selection and follow-up these findings.