A Phase II single-arm trial of palonosetron for the prevention of acute and delayed chemotherapy-induced nausea and vomiting in malignant glioma patients receiving multidose irinotecan in combination with bevacizumab

Abstract

PurposeGiven that the prognosis of recurrent malignant glioma (MG) remains poor, improving quality of life (QoL) through symptom management is important. Meta-analyses establishing antiemetic guidelines have demonstrated the superiority of palonosetron (PAL) over older 5-hydroxytryptamine 3-receptor antagonists in chemotherapy-induced nausea and vomiting (CINV) prevention, but excluded patients with gliomas. Irinotecan plus bevacizumab is a treatment frequently used in MG, but is associated with low (55%) CINV complete response (CR; no emesis or use of rescue antiemetic) with commonly prescribed ondansetron. A single-arm Phase II trial was conducted in MG patients to determine the efficacy of intravenous PAL (0.25 mg) and dexamethasone (DEX; 10 mg) received in conjunction with biweekly irinotecan–bevacizumab treatment. The primary end point was the proportion of subjects achieving acute CINV CR (no emesis or antiemetic ≤24 hours postchemotherapy). Secondary end points included delayed CINV CR (days 2–5), overall CINV CR (days 1–5), and QoL, fatigue, and toxicity.Materials and methodsA two-stage design of 160 patients was planned to differentiate between CINV CR of 55% and 65% after each dose of PAL–DEX. Validated surveys assessed fatigue and QoL.ResultsA total of 63 patients were enrolled, after which enrollment was terminated due to slow accrual; 52 patients were evaluable for the primary outcome of acute CINV CR. Following PAL–DEX dose administrations 1–3, acute CINV CR rates were 62%, 68%, and 70%; delayed CINV CR rates were 62%, 66%, and 70%, and overall CINV CR rates were 47%, 57%, and 62%, respectively. Compared to baseline, there was a clinically meaningful increase in fatigue during acute and overall phases, but not in the delayed phase. There were no grade ≥3 PAL–DEX treatment-related toxicities.ConclusionData suggest that PAL–DEX is effective in preventing CINV in MG patients, which ultimately maintains the QoL of patients with glioma.

Treatment efficacy and safety of regorafenib plus drug-eluting beads-transarterial chemoembolization versus regorafenib monotherapy in colorectal cancer liver metastasis patients who fail standard treatment regimens

“…Partly in line with previous studies (Fiorentini et al 2008(Fiorentini et al , 2009, we found that the most commonly occurred adverse events related to regorafenib were hand-food-skin reaction and fatigue, while those related to DEB-TACE was upper abdominal distending pain in CRLM patients who fail standard treatment regimens. Notably, regorafenib plus DEB-TACE treatment induced more upper abdominal distending pain, nausea, and vomiting, as well as fever compared with regorafenib monotherapy in CRLM patients who fail standard treatment regimens, among which upper abdominal distending pain and fever might be related to the necrosis and inflammation in tumor tissues induced by the hypoxia effect of embolization of DEB-TACE (Fiorentini et al 2008;Fiorentini et al 2009), and nausea and vomiting could be induced by irinotecan loaded by DEB-TACE, which is wellillustrated by previous studies (Affronti 2017;Suzuki et al 2016). Besides, regorafenib plus DEB-TACE treatment did not induce additional grade ≥ 3 adverse events or abnormality in liver function compared with regorafenib treatment monotherapy, which implied that regorafenib plus DEB-TACE treatment was generally tolerable in CRLM patients who failed standard treatment regimens.…”

WZY-321 triggers glioma cell apoptosis via XAF1 up-regulation caused by MTM-mediated miR-873 down-regulation

“…Gliomas account for the majority of primary malignant brain tumors around the world and are highly aggressive [1][2][3][4]. Gliomas usually originate from glial, choroid plexus epithelium, ependymal, neurons, etc., accounting for about 45% of all intracranial tumors.…”

Efficacy and safety of long-term therapy for high-grade glioma with temozolomide: A meta-analysis

“…Glioma is the most common primary tumor in the central nervous system (CNS). It accounts for nearly 80% [ 1 , 2 ]. The HGG patients have a median survival of 15 months [ 3 ].…”