Discussion
nausea, oral mucositis, emesis, nausea and vomiting, gastrointestinal toxic, vomiting, CINV, HNSCC, nausea and vomiting symptoms
ORAL MUCOSITIS
To our knowledge, this randomized clinical trial is the first study to assess the efficacy and safety of fosaprepitant during combined radiotherapy-HEC. Although there was no statistically significant difference in the complete response primary end point, we found that weekly fosaprepitant was more effective in providing sustained protection against emesis and significant nausea than fosaprepitant every 3 weeks. The interactions between treatment effects and mean brainstem dose of 36 Gy or more indicated the benefit of intensified weekly fosaprepitant was more evident in the subgroup with a mean brainstem dose of at least 36 Gy. The tolerability profile, quality-of-life data, and survival outcomes showed that weekly fosaprepitant was well tolerated and improved quality of life of patients without compromising survival.To our knowledge, there has been no evidence for the best antiemetic prophylaxis during combined radiotherapy-HEC. Several studies established a 3-drug combination regimen to prevent the nausea and vomiting in patients receiving HEC or moderately emetogenic chemotherapy during the first 120 hours after initiation of chemotherapy.In this study, the weekly fosaprepitant regimen provided no significant improvements in sustained no emesis and no significant nausea during CCRT, except before day 1 and days 1 to 7 postcisplatin in cycle 1. This finding suggests that the weekly administration of fosaprepitant was effective for the prevention of emesis and significant nausea after days 1 through 7 and during CCRT. Furthermore, there is now a consensus that the prevention of CINV should be assessed during the acute (day 1), delayed (days 2-5), and overall (days 1-5) phases, especially when considering that the time to first emesis rarely exceeds 5 days. In this study, the mean time to first emesis was 26.5 days in the weekly fosaprepitant group and 15.6 days in the fosaprepitant every 3 weeks group. These results highlight the value of weekly administration of fosaprepitant during combined radiotherapy-HEC due to the increased risk of emesis beyond the first 7 days of the first cycle of cisplatin.Currently, prevention and control of nausea are more challenging than prevention and control of vomiting.The tolerability profiles in both groups were similar and were mostly associated with the chemotherapeutic agents. We observed a significant improvement in most of the quality-of-life scales in the weekly group owing to the reduction in gastrointestinal toxic effects. Moreover, the adherence rate of weekly fosaprepitant was satisfactory, probably because the IV administration of fosaprepitant provided greater treatment flexibility and convenience for patients with oral mucositis who could not tolerate oral medications.A possible treatment interaction effect on sustained complete response and sustained no emesis in the mean brainstem dose subgroups was observed. The benefit of weekly fosaprepitant was more evident in patients with a mean brainstem dose of 36 Gy or greater. It is interesting to note that areas connected to the development of emesis also exist in the brainstem. Multiple studies have reported a radiation dose–response association of brainstem dose with nausea and vomiting symptoms, which may contribute to a higher incidence of nausea and vomiting in patients with HNSCC treated with IMRT; these results suggest that radiation dose to the brainstem outside of the target volume influences the incidence of vomiting during IMRT for HNSCC, including NPC.