Use of long term aprepitant as a treatment for refractory nausea following oesophageal stent insertion – a case report

Background: Aprepitant, a substance P neurokinin-1 receptor antagonist, is licenced for the prevention of acute and delayed nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy. Case: A 33 year-old male with metastatic gastro-oesophageal cancer had multiple admissions for refractory nausea and vomiting following insertion of an oesophageal stent. Action: Mechanical issues with the stent, stent removal and central causes were excluded. Multiple anti-emetic agents were trialled in combination and with varying routes of administration without significant symptomatic improvement. Formulation: A trial of aprepitant was proposed as an off-licence therapy. Outcome: One hundred sixty-five milligrammes of aprepitant was given orally every 3 days and then up titrated to once daily with significant symptomatic improvement enabling the patient to tolerate an oral diet. The patient remained stable at 12 weeks and has been accepted into two clinical trials for potential further cancer treatment. Lessons: Aprepitant can be effective in refractory nausea and vomiting outside of emetogenic chemotherapy and safely used as a chronic treatment. The prevalence of refractory nausea and vomiting as a rare adverse outcome post-oesophageal stent insertion should be studied. What now? Further research of neurokinin-1 inhibitors for indications other than chemotherapy-induced nausea and vomiting is indicated.

Pooled analysis of combination antiemetic therapy for chemotherapy-induced nausea and vomiting in patients with colorectal cancer treated with oxaliplatin-based chemotherapy of moderate emetic risk

Background Among patients with colorectal cancer (CRC) treated with oxaliplatin (L-OHP)-based chemotherapy, delayed chemotherapy-induced nausea and vomiting (CINV) have not been well controlled. Methods We pooled data from two prospective observational studies in Japan and one phase III clinical trial to assess whether delayed CINV could be controlled with a combination of three antiemetics adding a neurokinin-1 receptor antagonist and identified individual risk factors, using an inverse probability treatment-weighted analysis. Results A total of 661 patients were evaluable in this study (median age: 64 years; 391 male, and 270 female). 3 antiemetics controlled delayed nausea (33.18% vs. 42.25%; p = 0.0510) and vomiting (4.15% vs. 16.08%; p < 0.0001) better than with 2 antiemetics. Female and 2 antiemetics were risk factors for both delayed nausea (female—odds ratio [OR]: 1.918; 95% confidence interval [CI]: 1.292–2.848; p = 0.0012; 2 antiemetics—OR: 1.485; 95% CI: 1.000–2.204; p = 0.0498) and delayed vomiting (female—OR: 2.735; 95% CI: 1.410–5.304; p = 0.0029; 2 antiemetics—OR: 4.551; 95% CI: 2.116–9.785; p = 0.0001). Conclusions Identifying individual risk factors can facilitate personalized treatments for delayed CINV. We recommend a 3-antiemetic combination prophylaxis for CRC patients treated with L-OHP-based chemotherapy, especially for female patients.

Efficacy of Auricular Acupressure in Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting in Patients with Cancer: A Systematic Review and Meta-Analysis

Background. More than 40% of patients with cancer have reported that chemotherapy-induced nausea and vomiting (CINV) remained the most debilitating side effects of treatment even in the era of new antiemetics. Objective. The purpose of this review was to systematically evaluate the clinical effect of auricular acupressure (AA) in prevention and treatment of chemotherapy-induced nausea and vomiting. Methods. The following databases were searched: PubMed, Cochrane Library, EMBASE, the Web of Science, Chinese Biological Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang, and VIP (from database inception to April 2020). Eligible randomized controlled trials of auricular acupressure in treating CINV were collected, including crossover randomized design study. The meta-analysis was carried out by RevMan software (5.3). Results. Totally 19 RCTs with 1449 patients met the inclusion criteria. Compared with control groups, the relief efficiency of overall CINV was enhanced by AA combined with antiemetics (RR = 1.31, CI 1.22 to 1.41, p ≤ 0.001). Although the therapeutic effect on acute nausea and vomiting was not obvious, AA still played an important role in reducing delayed nausea and vomiting (delayed nausea frequency: RR = 0.68, CI −1.01 to −1.35, p ≤ 0.001; delayed vomiting frequency: RR = 0.91, CI −1.22 to −0.61, p ≤ 0.001). The likelihood of adverse reactions related to antiemetics was reduced by AA combined with antiemetics (RR = 0.62, CI 0.53 to 0.74, p ≤ 0.001). Statistically significant association was found between AA and incidence of constipation, diarrhea, and tiredness, while there was no statistically significant association between AA and abdominal distension or headache. Conclusion. Auricular acupressure supplementation benefited delayed chemotherapy-induced nausea and vomiting as well as constipation, diarrhea, and tiredness. AA alone or AA supplementation has little effect on acute nausea and acute vomiting. There is no conclusion on whether AA alone is superior to antiemetics in the management of delayed CINV. Further studies are needed to confirm the efficacy of auricular acupressure alone in delayed CINV and anticipatory CINV. The results of this review provided the basis for further research with more rigorous study designs, adequate sample sizes, and standardized implementation to confirm the efficacy of auricular acupressure.

ICES (International Carboplatin Emesis Survey) for the evaluation of the emetogenicity of continuous cycles of carboplatin-based chemotherapy with focus on nausea: A MASCC emesis study group, prospective, observational, real-world multi-centric study.

e24086 Background: Chemotherapy induced nausea and vomiting (CINV) following carboplatin containing chemotherapy regimen remains a considerable problem for cancer patients (pts) despite standard antiemetic prophylaxis. This study was undertaken to prospectively evaluate the incidence of CINV in pts undergoing carboplatin-based chemotherapy receiving guidelines consistent CINV prophylaxis (GCCP). All sites did not prescribe NK1-RA as it is not included in all institutional guidelines. Methods: The study enrolled 207 pts undergoing carboplatin-based chemotherapy, the final analysis evaluated cycle 1 - 6 with a total of 183 evaluable pts from 6 countries. Pt diaries were used to collect data from day 1-10 beginning with cycle 1. Nausea was reported by the pts using a visual analog scale (VAS) with the end-point being no nausea. Vomiting episodes were recorded in the pts’ diaries. Demographic, occurrence and severity of emesis, numbers of emetic episodes and time to the onset of emesis, were summarized using descriptive statistics. Results: There were 129 females and 54 males. The overall incidence of acute and delayed nausea for was 17% and 25% respectively. The incidence of nausea of entire population was significantly higher than vomiting (58% vs. 14%; Chi2 22.271 p<0.000). The use of NK1-RA was associated with a significant decrease in time to first vomiting for cycle 1 (p<0.041) and subsequent cycle 2-6 (p<0.0075). Additional results are reported in the Table. In a logistic regression model factors associated with acute nausea in cycle 1 included history of motion sickness (p< 0.0090), comorbidities (p< 0.0084), history of morning sickness (p< 0.0090), previous chemotherapy (p< 0.0096), anemia (p< 0.0209). A separate logistic regression analysis for delayed nausea in cycle 1 showed that prior radiotherapy (p<0.0093) and a history of morning sickness (p<0.0195) were also significant. During subsequent cycles (1 – 6), the incidence of nausea remained higher than vomiting and was documented in the acute and delayed phases ranging from 6% to 25%. The use of NK1-RA was associated with a lower incidence of vomiting during cycle 1-6 with 91% patient receiving NK1-RA experiencing no vomiting vs 78% of patients not receiving NK1-RA with no vomiting (log rank = 0.0287). Conclusions: Despite GCCP and the usage of NK1-RA, carboplatin induced nausea remains a major unmet medical need in cancer pts. Further research should focus on management of nausea, risk factors and the impact of nausea on quality of life and in pts undergoing carboplatin-based treatment.[Table: see text]

Single-dose netupitant/palonosetron versus 3-day aprepitant for preventing chemotherapy-induced nausea and vomiting: a pooled analysis

Aim: In the absence of comparative studies, guidelines consider neurokinin 1 receptor antagonists (RAs) as interchangeable. We evaluated the pooled efficacy from three cisplatin registration trials, each with arms containing netupitant/palonosetron (NEPA), a fixed neurokinin 1 RA (netupitant)/serotonin Type 3 (5-HT3) RA (palonosetron) combination, and an aprepitant (APR) regimen. Materials & methods: Efficacy data were pooled for rates of complete response (CR: no emesis/no rescue medication), complete protection (CR + no significant nausea), total control (CR + no nausea) and no significant nausea during acute (0–24 h), delayed (>24–120 h) and overall (0–120 h) phases post chemotherapy. Results: Among 621 NEPA and 576 APR patients, response rates were similar for the acute phase, and generally favored NEPA during delayed and overall phases. CR rates for NEPA versus APR were 88.4 versus 89.2%, 81.8 versus 76.9% (p < 0.05) and 78.4 versus 75.0% during the acute, delayed and overall phases, respectively. Conclusion: Oral NEPA administered on day 1 was more effective than a 3-day APR regimen in preventing delayed nausea and vomiting associated with cisplatin.

The Emesis Trial: Depressive Patients with Brain Tumors are more Affected by Chemotherapy-induced Nausea and Vomiting

Purpose: Patients with malignant brain tumors face a limited life expectancy and at the same time, they suffer from afflicting symptoms and undesired effects of tumor treatment. Apart from bone marrow suppression, standard chemotherapy with temozolomide causes nausea, emesis and loss of appetite. In this pilot study, we investigated how chemotherapy-induced nausea and vomiting (CINV) affects the patients’ levels of depression and their quality of life. Methods: In this prospective observational multicentre study (n = 87), nausea, emesis and loss of appetite were evaluated with an expanded MASCC questionnaire, covering ten days during the first and the second cycle of chemotherapy. Quality of life was assessed with the EORTC QLQ-C30 and BN 20 questionnaire and levels of depression with the PHQ-9 inventory before and after the first and second cycle of chemotherapy. Results: CINV affected a minor part of patients. If present, it reached its maximum at day 3 and decreased to baseline level not before day 8. Levels of depression increased significantly after the first cycle of chemotherapy, but decreased during the further course of treatment. Patients with higher levels of depression were more severely affected by CINV and showed a lower quality of life through all time-points. Conclusion: We conclude that symptoms of depression should be perceived in advance and treated in order to avoid more severe side effects of tumor treatment. Additionally, in affected patients, delayed nausea was most prominent, pointing towards an activation of the NK1 receptor. We conclude that long acting antiemetics are necessary to treat temozolomide-induced nausea.

Chemotherapy-induced nausea and vomiting (CINV) with carboplatin plus pemetrexed or carboplatin plus paclitaxel in patients with lung cancer: a propensity score-matched analysis

Background Patients with lung cancer who are treated with carboplatin-based chemotherapy regimens often experience chemotherapy-induced nausea and vomiting (CINV). However, knowledge on the effect of regimen and cofactors on the risk of CINV is limited. This study aimed to analyze and compare the incidence of CINV between lung cancer patients undergoing carboplatin plus pemetrexed (CBDCA+PEM) and those undergoing carboplatin plus paclitaxel (CBDCA+PTX) chemotherapy. Methods Pooled data of 240 patients from two prospective observational studies were compared using propensity score matching. Separate multivariate logistic regression analyses were used to identify risk factors for nausea and vomiting following chemotherapy. Results Delayed nausea was significantly more common in patients treated with CBDCA+PEM than in those treated with CBDCA+PTX (51.1% vs. 36.2%, P = 0.04), but the incidence of vomiting did not significantly differ between the two groups (23.4% vs. 14.9%, P = 0.14). The occurrence of CINV peaked on day 4 in the CBDCA+PTX group and on day 5 in the CBDCA+PEM group. Multivariate analysis showed that female sex, younger age, and CBDCA+PEM regimen were independent risk factors for delayed nausea, while female sex was an independent risk factor for delayed vomiting. Conclusions The CBDCA + PEM regimen has a higher risk of causing delayed nausea than the CBDCA + PTX regimen, and aggressive antiemetic prophylaxis should be offered to patients treated with CBDCA + PEM.

Analysis of Antiemetic Premedication Administration Timing on Nausea and Vomiting Incidence among Breast Cancer Patients Receiving Chemotherapy

The risk factors affecting chemotherapy-induced nausea and vomiting (CINV) includes antiemetic premedication time pattern, and this study investigates the capability of enhancing this in breast cancer patients receiving high emetogenic chemotherapy (HEC). Furthermore, this observational research was implemented at the oncology unit of Dr. Soetomo General Hospital Surabaya over a three-month period involving 69 female patients. The results showed unspecific antiemetic premedication timing in comparison to those with recommended timeframes, was connected with greater occurrence of both acute nausea in all cycles of chemotherapy (p<0.05), and acute vomiting in second and third cycles (p<0.05) but not in the first cycle (p=0.49). However, specific time administration of antiemetic treatment was linked with lower incidence of delayed nausea in all cycles (p<0.05), and less delayed vomiting in second and third cycles (p<0.05) but not in first cycle (p=0.10). These findings indicate specific time administration of antiemetic drugs causes significant advantages in mitigating CINV among breast cancer patients treated with emetogenic chemotherapy, and significantly lessened the occurrence of acute and delayed nausea and vomiting.Keywords: Antiemetic premedication timing, breast cancer, CINV, nausea and vomiting Analisis Waktu Pemberian Premedikasi Antiemetik terhadap Kejadian Mual Muntah pada Pasien Kanker Payudara yang Mendapatkan Kemoterapi AbstrakKemoterapi dapat menginduksi mual muntah (chemotherapy-induced nausea and vomiting, CINV) yang dipengaruhi oleh beberapa faktor. Salah satu faktornya adalah waktu pemberian premedikasi antiemetik yang dapat meningkatkan kejadian CINV pada pasien kanker payudara yang menerima kemoterapi. Studi ini menganalisis waktu pemberian premedikasi antiemetik terhadap kejadian mual dan muntah yang terjadi pada pasien kanker payudara yang mendapatkan kemoterapi dengan tingkat emetogenik yang tinggi. Penelitian ini merupakan penelitian observasional prospektif dilakukan di Poli Onkologi Satu Atap RSUD Dr. Soetomo Surabaya selama periode pengambilan data tiga bulan dan melibatkan 69 wanita kanker payudara yang mendapat kemoterapi dengan tingkat emetogenik yang tinggi. Pemberian premedikasi antiemetik dengan waktu yang tidak spesifik, meningkatkan kejadian mual akut pada semua siklus dengan p<0,05 dan pada kejadian muntah akut pada siklus kedua dan ketiga (p<0,05), namun tidak pada siklus pertama kemoterapi (p=0,49). Pemberian premedikasi antiemetik dengan waktu spesifik dapat menurunkan kejadian mual tertunda di siklus pertama hingga ketiga (p<0,05) dan pada kejadian muntah tertunda pada siklus kedua dan ketiga (p<0,05), namun tidak pada siklus pertama (p=0,10). Penelitian ini memberikan bukti bahwa premedikasi antiemetik yang diberikan dengan waktu spesifik memberikan manfaat dalam mengurangi kejadian CINV yang berpotensi pada pasien kanker payudara yang mendapatkan kemoterapi dengan tingkat emetogenik tinggi. Kata kunci: CINV, kanker payudara, mual dan muntah, waktu pemberian premedikasi antiemetik

The effect of foot reflexology on chemotherapy-induced nausea and vomiting in digestive or lung cancer patients: a randomized controlled trial (Preprint)

BACKGROUND Cancer is a chronic disease with an incident worldwide had been 24.5 million and 9.6 million deaths in 2017. Lung and colorectal cancer are the most common cancer for both sexes and according to national and international recommendations platinum-based chemotherapy is the reference adjuvant treatment. This chemotherapy can be moderately to highly emetogenic. Despite antiemetic therapy, chemotherapy-induced nausea and vomiting may persist. Moreover, cancer patient are increasingly interested in alternative and complementary medicines and express the desire that non-pharmacological treatments be used in hospitals. Among alternative and complementary medicines, foot reflexology decreases significantly the severity of chemotherapy-induced nausea and vomiting in breast cancer patients. OBJECTIVE The primary objective of the present study was to assess the benefits of foot reflexology as a complement to conventional treatments on severity of acute chemotherapy-induced nausea and vomiting in digestive or lung cancer patients. The secondary objectives assessed were the frequency and severity of delayed chemotherapy-induced nausea and vomiting, quality of life, anxiety, and self-esteem. METHODS The present study was conducted between April 2018 and April 2020 in French University Hospital. This is an open-label randomized controlled trial. Participants are randomized into two groups: 40 to interventional group (conventional care with foot reflexology) and 40 to control group (conventional care without foot reflexology). Foot reflexology sessions (30 minutes) are performed on an outpatient or inpatient. Eligible participants are patients with a lung or digestive cancer with indication for platinum-based chemotherapy. RESULTS The severity of acute nausea and vomiting was assessed with a visual analogue scale during the second cycle of chemotherapy. A significant increase of at least 2 points was observed for control group (20.6%, P = 0.01). Across all cycle, the foot reflexology group showed a trend towards less frequent delayed nausea (P=0.28), a significantly less frequent consumption of antiemetic drugs (P=0.04), and no significant difference for vomiting (P=0.99); there was a trend towards a perception of stronger severity for delayed nausea in the control group (P=0.39). According to quality of life and anxiety, there was no significant difference between the interventional group and the control group (P=0.32 and P=0.53 respectively). CONCLUSIONS In conclusion, the present study results indicated that foot reflexology decreased significantly the severity of acute nausea and consumption of antiemetic drugs in lung and digestive cancer patients. No side effects from foot reflexology have been noted. In order to better respond to a desire of patients for non-pharmacological treatments and CAMs to be used in hospitals to improve their care, the results of this study showed that foot reflexology seems to be a promising complement to conventional antiemetic drugs. To assess the performance of this intervention in routine practice, a larger study with several health care centers would be relevant with a cluster RCT. CLINICALTRIAL The present study registered with clinicaltrials.gov: NCT03508180 (28/06/2018) INTERNATIONAL REGISTERED REPORT RR2-10.2196/17232

Chemotherapy-Induced Nausea and Vomiting (CINV) with GI Cancer Chemotherapy: Do We Need CINV Risk Score Over and Above Antiemetic Guidelines in Prescribing Antiemetic Regime?

Background Various predictive models have been developed which incorporates patient risk factors into the selection of optimal antiemetic therapy, one of which is chemotherapy-induced nausea and vomiting (CINV) risk scoring system developed by Multinational Association of Supportive Care in Cancer (MASCC). Patients and Methods Consecutive patients with gastrointestinal malignancy who had not received previous chemotherapy were eligible for enrollment in the study if they were scheduled to receive at least one cycle of chemotherapy. The CINV risk assessment tool was used to collect the study data and to assess CINV risk score. Results Ninety-eight patients fulfilling the eligibility criteria were included in this study, out of which 57% were males, median age was 48 years (range: 28–77). Colorectal cancer (32.7%) was the most common diagnosis followed by gastric cancer (27.6%). Gemcitabine/cisplatin and CAPOX regimen were the most common regimen being administered in 19.4% each. As per MASCC guidelines, 19.4% patients received highly emetogenic chemotherapy, 69.4% moderately emetogenic chemotherapy, while 11.2% received regimen with low emetogenicity. CINV risk module characterized 52% patients to have high risk for CINV, while 48% to have low risk of CINV, thus, 52% had the discrepancy in risk assigned by two methods, and this was statistically significant (p = 0.025). In subgroup analysis, although patient cohort with acute nausea had no statistically significant discrepancy (p = 0.123), but statistically significant discrepancy was found in patient cohort with delayed nausea (p = 0.001), acute (p = 0.038), and delayed (p < 0.001) vomiting. Conclusion A significant percentage of patients who receive chemotherapy continue to experience nausea and vomiting despite receiving antiemetic treatment as per standard guidelines. The study generates a hypothesis for future large randomized studies looking at change in antiemetic prophylaxis based on CINV risk tool, leading to improvement in complete response rates of acute and delayed CINV.