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Aprepitant in weekly cisplatin with radiation in head and neck cancer: Is it required?
Abstract
e24122
Background: Weekly cisplatin below 50 mg/m2 has lower emetogenic potential than 100 mg/m2 3weekly regimen. There is limited data on the utility of Aprepitant with weekly cisplatin used in radiation in head and neck squamous cell cancer (HNSCC). Methods: We conducted a phase 3 randomized trial in locally advanced HNSCC patients who were treated with definitive chemoradiation either with cisplatin or cisplatin-nimotuzumab. 5HT3 inhibitor and steroids +/- aprepitant were used as antiemetic prophylaxis as per physician discretion. The current analysis is focussed on studying the impact of aprepitant on nausea and vomiting. Fischer’s exact test was used to compare the chemotherapy induced nausea vomiting (CINV) rates between aprepitant and non-aprepitant groups. Binary logistic regression analysis was used to calculate the odds of CINV with the use of aprepitant. Results: Data on CINV is available for 524/536 patients. Nausea was present in 251 (47.9%) patients while vomiting was seen in 155 (29.6%) patients. Aprepitant, 5HT3 antagonist and dexamethasone were administered to 265 (50.86%), while 256 received 5HT3 antagonist and dexamethasone. Among patients receiving aprepitant, nausea was present in 112 (42.3%), while there was no nausea in 153 (57.7%) patients (p = 0.011). Vomiting with aprepitant was seen in 71 (26.8%) patients while 194 (73.2%) had no vomiting (p = 0.151). Adjusted odds ratio for use of aprepitant containing antiemetic prophylaxis in prevention of CINV were 1.585 (1.116-2.249;p = 0.010) and 1.328 (0.904-1.951;p = 0.149) as depicted in the table. Conclusions: Use of aprepitant significantly decreases nausea and is needed for weekly cisplatin regimens used in radiation in head and neck cancers. [Table: see text]
... However, this issue is underexplored in head and neck cancer patients. Only five prospective studies have investigated the efficacy and safety of NK1 RAs in the prophylaxis of CINV, which were focused on multiplesite tumors [25][26][27][28][29][30][31]. These studies showed that NK1 RAs are superior to other treatments in preventing nausea and vomiting, and are well tolerated. ...
... This study investigated the rate of CINV in head and neck cancer patients undergoing prophylaxis with triple agents for CRT. We resumed the main data available from the literature in Table 3 [25,27,[30][31][32]. ...
... According to data of a recent phase III trial, the use of aprepitant significantly decreases nausea and should be adopted for weekly cisplatin regimens used in HNSCC RT. Indeed, after the comparison of two schedules for CINV control with or without aprepitant combined with 5HT3 antagonist and dexamethasone, D'souza et al. [31] reported a rate of nausea of 42.3% in the aprepitant group vs 47.9% in the control group. Stinson et al. [32] evaluated two strategies of prophylaxis of acute and late CINV in a retrospective cohort of HNSSC patients undergoing CRT collecting a nausea rate of 38.5%. ...
Cisplatin-based chemoradiotherapy (CRT) is standard treatment for head and neck squamous cell carcinoma (HNSCC). However, IMRT may increase chemotherapy-induced nausea and vomiting (CINV). The purpose of this study is to investigate the effect of fosaprepitant in preventing CINV.
An infusion of 150 mg fosaprepitant was given through a 30 min. We assessed acute toxicity using CTCAE v.4 and the incidence of CINV using the FLIE questionnaire. The evaluation of CINV was done at the second and fifth weeks of CRT and 1 week after the end. The EORTC QLQ-HN 43 questionnaire was administered before treatment beginning (baseline), at second (T1) and fifth (T2) weeks. A dosimetric analysis was performed on dorsal nucleus of vagus (DVC) and area postrema (AP).
Between March and November 2020, 24 patients were enrolled. No correlation was found between nausea and DVC mean dose (p = 0.573), and AP mean dose (p = 0.869). Based on the FLIE questionnaire, patients reported a mean score of 30.5 for nausea and 30 for vomiting during week 2 and 29.8 for nausea and 29.2 for vomiting during week 5. After treatment ended, the mean scores were 27.4 for nausea and 27.7 for vomiting. All patients completed the EORTC QLQ-HN 43. Significantly higher scores at T2 assessment than baseline were observed.
The use of fosaprepitant in preventing CINV reduced incidence of moderate to severe nausea and vomiting. No correlation has been found between nausea and median dose to DVC and AP.
... Conversely, "no vomiting" and "no nausea" are relatively objective indicators, being adopted as secondary endpoints in our study. In the overall phase, 88.4% of patients developed no emesis, higher than the 66-73% reported in previous studies on NK1RAs for prevention of C-RINV [15,17,18,31]. Although the overall nausea-free response rate was only 60.5%, this is approximately consistent with the 40-61.5% reported in preceding research on NK1RAs for prevention of C-RINV [16,18,31]. ...
... In the overall phase, 88.4% of patients developed no emesis, higher than the 66-73% reported in previous studies on NK1RAs for prevention of C-RINV [15,17,18,31]. Although the overall nausea-free response rate was only 60.5%, this is approximately consistent with the 40-61.5% reported in preceding research on NK1RAs for prevention of C-RINV [16,18,31]. ...
... Recently, another prospective study evaluating the antiemetic efficacy of aprepitant in patients with LA-HNSCC receiving radiotherapy and concurrent weekly cisplatin (50 mg/m 2 ) chemotherapy was exhibited at the 2020 Annual Meeting of the American Society of Clinical Oncology (ASCO) [31]. The incidences of no nausea and no vomiting were 57.7 and 73.2%, respectively, in patients receiving aprepitant, 5-HT3RA, and steroids. ...
Background
There is sparse research reporting effective interventions for preventing nausea and emesis caused by concurrent chemoradiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC).
Methods
Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concomitant cisplatin 100 mg/m² (33 mg/m²/days [d]1–3) every 3 weeks for two cycles. All patients were given oral aprepitant 125 mg once on d1, then 80 mg once on d2–5; ondansetron 8 mg once on d1; and dexamethasone 12 mg once on d1, then 8 mg on d2–5. The primary endpoint was complete response (CR). Pursuant to δ = 0.2 and α = 0.05, the expected CR rate was 80%.
Results
A total of 43 patients with LA-HNSCC were enrolled. The median age was 53 years, and 86.0% were male. All patients received radiotherapy and 86.0% of patients completed both cycles as planned. The overall CR rate was 86.0% (95% confidence interval [CI]: 72.1–94.7). The CR rates for cycles 1 and 2 were 88.4% (95% CI: 74.9–96.1) and 89.2% (95% CI: 74.6–97.0). The complete protection rate in the overall phase was 72.1% (95% CI: 56.3–84.7). The emesis-free and nausea-free responses in the overall phase were 88.4% (95% CI: 74.9–96.1) and 60.5% (95% CI: 44.4–75.0), respectively. The adverse events related to antiemetics were constipation (65.1%) and hiccups (16.3%), but both were grade 1–2. There was no grade 4 or 5 treatment-related toxicity with antiemetic usage.
Conclusion
The addition of aprepitant into ondansetron and dexamethasone provided effective protection from nausea and emesis in patients with LA-HNSCC receiving radiotherapy and concomitant high-dose cisplatin chemotherapy.
... Conversely, "no vomiting" and "no nausea" are relatively objective indicators, being adopted as secondary endpoints in our study. In the overall phase, 88.4% of patients developed no emesis, higher than the 66%-73% reported in previous studies on NK 1 RAs for prevention of C-RINV [1,5,13,27]. Although the overall nausea-free response rate was only 60.5%, this is approximately consistent with the 40%-61.5% reported in preceding research on NK 1 RAs for prevention of C-RINV [1,5,21]. ...
... In the overall phase, 88.4% of patients developed no emesis, higher than the 66%-73% reported in previous studies on NK 1 RAs for prevention of C-RINV [1,5,13,27]. Although the overall nausea-free response rate was only 60.5%, this is approximately consistent with the 40%-61.5% reported in preceding research on NK 1 RAs for prevention of C-RINV [1,5,21]. ...
... Recently, another prospective study evaluating the antiemetic e cacy of aprepitant in patients with LA-HNSCC receiving radiotherapy and concurrent weekly cisplatin (50 mg/m 2 ) chemotherapy was exhibited at the 2020 Annual Meeting of the American Society of Clinical Oncology (ASCO) [5]. The incidences of no nausea and no vomiting were 57.7% and 73.2% in patients receiving aprepitant, 5-HT 3 RA and steroids. ...
Purpose To provide a direct evidence for the current practice of prescribing antiemetic with aprepitant, dexamethasone and ondansetron in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) receiving concurrent chemoradiotherapy (CCRT).
Methods Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concomitant cisplatin 100 mg/m² every 3 weeks for two cycles. All patients were given orally aprepitant 125 mg once on d1, then 80mg once on d2-5; ondansetron 8 mg once on d1; and dexamethasone 12 mg once on d1, then 8mg on d2-5. The primary endpoint was complete response (CR). Pursuant to δ=0.2 and α=0.05, the expected CR rate was 80%.
Results A total of 43 patients with LA-HNSCC were enrolled. The median age was 53 years old, and 86.0% were male. All patients received radiotherapy and 86.0% of patients completed both cycles as planned. The overall CR rate was 86.0% (95% CI: 72.1-94.7). The CR rates for cycles 1 and 2 were 88.4% (95% CI: 74.9-96.1) and 89.2% (95% CI: 74.6-97.0). The complete protection rate in the overall phase was 72.1% (95% CI: 56.3-84.7). The emesis-free response and nausea-free response in overall phase were 88.4% (95% CI: 74.9-96.1) and 60.5% (95% CI: 44.4-75.0), respectively. The adverse events related to antiemetics were constipation (65.1%) and hiccups (16.3%), but both were grade 1-2. There was no grade 4 or 5 treatment-related adverse event with antiemetic usage.
Conclusion The addition of aprepitant into ondansetron and dexamethasone provided effective protection from nausea and emesis in patients with LA-HNSCC receiving CCRT.
Trial registration ID: NCT03572829.
... Conversely, "no vomiting" and "no nausea" are relatively objective indicators, being adopted as secondary endpoints in our study. In the overall phase, 88.4% of patients developed no emesis, higher than the 66%-73% reported in previous studies on NK 1 RAs for prevention of C-RINV 15,17,18,27 . Although the overall nausea-free response rate was only 60.5%, this is approximately consistent with the 40%-61.5% reported in preceding research on NK 1 RAs for prevention of C-RINV 16, 18, 27 . ...
... Conversely, the majority of patients with nausea presented mainly mild and moderate levels in the present study. Despite the determination of the degree of nausea being subjective, only one patient required rescue antiemetics, and no patient discontinued treatment due to nausea or vomiting, thereby objectively illustrating that the triple regimen containing aprepitant could effectively control the occurrence of severe nausea and vomiting.Recently, another prospective study evaluating the antiemetic e cacy of aprepitant in patients with LA-HNSCC receiving radiotherapy and concurrent weekly cisplatin (50 mg/m 2 ) chemotherapy was exhibited at the 2020 Annual Meeting of the American Society of Clinical Oncology (ASCO)27 . The incidences of no nausea and no vomiting were 57.7% and 73.2% in patients receiving aprepitant, 5-HT 3 RA and steroids. ...
Background There is sparse research reporting effective interventions for preventing nausea and emesis caused by concurrent chemoradiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This phase Ⅱ trial was conducted to provide the direct evidence for the current practice of prescribing antiemetic in patients with LA-HNSCC receiving CCRT.
Methods Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concomitant cisplatin 100 mg/m² every 3 weeks for two cycles. All patients were given orally aprepitant 125 mg once on d1, then 80mg once on d2-5; ondansetron 8 mg once on d1; and dexamethasone 12 mg once on d1, then 8mg on d2-5. The primary endpoint was complete response (CR). Pursuant to δ=0.2 and α=0.05, the expected CR rate was 80%.
Results A total of 43 patients with LA-HNSCC were enrolled. The median age was 53 years old, and 86.0% were male. All patients received radiotherapy and 86.0% of patients completed both cycles as planned. The overall CR rate was 86.0% (95% CI: 72.1-94.7). The CR rates for cycles 1 and 2 were 88.4% (95% CI: 74.9-96.1) and 89.2% (95% CI: 74.6-97.0). The complete protection rate in the overall phase was 72.1% (95% CI: 56.3-84.7). The emesis-free response and nausea-free response in overall phase were 88.4% (95% CI: 74.9-96.1) and 60.5% (95% CI: 44.4-75.0), respectively. The adverse events related to antiemetics were constipation (65.1%) and hiccups (16.3%), but both were grade 1-2. There was no grade 4 or 5 treatment-related adverse event with antiemetic usage.
Conclusion The addition of aprepitant into ondansetron and dexamethasone provided effective protection from nausea and emesis in patients with LA-HNSCC receiving radiotherapy and concomitant high-dose cisplatin chemotherapy. Randomised phase 3 studies are required to further define the potential role of NK1RA in chemoradiotherapy setting.
Trial registration: ClinicalTrials.gov, number NCT03572829. Registered 28 June 2018, https://clinicaltrials.gov/ct2/show/NCT03572829?term=NCT03572829&draw=2&rank=1.
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