METHODS: This was a real-world study of a fixed-dose combination of netupitant and palonosetron (NEPA) to inhibit CINV in adult patients receiving moderately (MEC) or highly emetogenic chemotherapy (HEC) for solid/hematological malignancies at eight Malaysian centers. Each HEC/MEC cycle received one dose of NEPA + dexamethasone for CINV prevention. Complete response (no emesis, no rescue medication) (CR), no more than mild nausea (severity score ≤ 2.5), and complete control (CR) (no more than mild nausea) during the acute (0-24 h), delayed (25-120 h), and overall (0-120 h) phases post-chemotherapy were measured. Treatment-related adverse events (AEs) were recorded.
RESULTS: During March 2016-April 2018 (NMRR-17-3286-38282), NEPA + dexamethasone was administered to 54 patients (77.8% solid, 22.2% hematological malignancies). Note that 59.3% received HEC, while 40.7% received MEC regimen. During the overall phase of the first cycle, the majority had CR (77.8%), no more than mild nausea (74.1%), and complete control (61.1%). Seventeen patients received two consecutive cycles at any point of chemotherapy cycles. During the overall phases across two consecutive cycles, all patients achieved CR, and the majority reported no more than mild nausea and complete control. No grades 3-4 AEs were reported.
CONCLUSIONS: NEPA had sustained efficacy and tolerability at first administration and across two cycles of MEC/HEC for CINV prevention.
MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases to identify original studies reporting toxicity outcomes following PBT of primary NPC. Quality assessment was performed using NIH's Quality Assessment Tool. Reports were extracted for information on demographics, main results, and clinical and dose factors correlates. Meta-analysis was performed using the random-effects model.
RESULTS: Twelve studies were selected (six using mixed particle-photon beams, five performed comparisons to photon-based therapy). The pooled event rates for acute grade ≥2 toxicities mucositis, dermatitis, xerostomia weight loss are 46% (95% confidence interval [95% CI]-29%-64%, I2 = 87%), 47% (95% CI-28%-67%, I2 = 87%), 16% (95% CI-9%-29%, I2 = 76%), and 36% (95% CI-27%-47%, I2 = 45%), respectively. Only one late endpoint (xerostomia grade ≥2) has sufficient data for analysis with pooled event rate of 9% (95% CI-3%-29%, I2 = 77%), lower than intensity-modulated radiotherapy 27% (95% CI-10%-54%, I2 = 95%). For most endpoints with significant differences between the PBT and photon-based therapies, PBT resulted in better outcomes. In two studies where dose distribution was studied, doses to the organs at risk were independent risk factors for toxicities.
CONCLUSION: PBT may reduce the risk of acute toxicities for patients treated for primary NPC, likely due to dose reduction to critical structures. The pooled event rate for toxicities derived in this study can be a guide for patient counseling.