Comparative effectiveness of netupitant-palonosetron plus dexamethasone versus aprepitant-based regimens in mitigating chemotherapy-induced nausea and vomiting: a meta-analysis of randomized controlled trials.

BACKGROUND: Despite guidelines for managing chemotherapy-induced nausea and vomiting (CINV), there remains a need to clarify the optimal use of neurokinin-1 (NK1) receptor antagonists. Comparing the effectiveness of NEPA (netupitant-palonosetron) plus dexamethasone with other NK1 antagonist-based regimens combined with a 5HT3 receptor antagonist and dexamethasone is crucial for informed decision-making and improving patient outcomes. METHODS: We conducted a systematic review of the literature to assess randomized controlled trials (RCTs) comparing the efficacy, safety, and cost-effectiveness of NEPA plus dexamethasone and other NK1 antagonist-based regimens combined with a 5HT3 receptor antagonist and dexamethasone. PubMed, Embase, and the Cochrane Library databases were systematically searched, with the latest update performed in December 2023. Data on patient demographics, chemotherapy regimen characteristics, and outcomes were extracted for meta-analysis using a random-effects model. RESULTS: Seven RCTs were analyzed. NEPA plus dexamethasone showed superior efficacy in achieving complete response in the overall (risk ratio [RR], 1.15; 95% CI, 1.02--1.30) and delayed phases (RR, 1.20; 95% CI, 1.03-1.41) of chemotherapy. It was more effective in controlling nausea (overall phase RR, 1.20; 95% CI, 1.05-1.36; delayed phase RR, 1.21; 95% CI, 1.05-1.40) and reducing rescue therapy use (overall phase RR, 1.45; 95% CI, 1.07-1.95; delayed phase RR, 1.75; 95% CI, 1.10-2.78). Adverse event rates were comparable (RR, 1.03; 95% CI, 0.96-1.10). Subgroup analysis indicated NEPA's particular efficacy in patients receiving moderately emetogenic chemotherapy (RR, 1.31; 95% CI, 1.07-1.60). CONCLUSION: NEPA plus dexamethasone regimens exhibit superior efficacy in preventing CINV, supporting their preferential inclusion in prophylactic treatment protocols. Its effective symptom control, safety profile, and cost-effectiveness endorse NEPA-based regimens as a beneficial option in CINV management.

NHS-Reimbursed Cannabis Flowers for Cancer Palliative Care and the Management of Chemotherapy-Induced Nausea and Vomiting: An Autobiographical Case Report.

Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of cancer treatment, affecting many patients. Cannabinoid agonists, such as nabilone and Δ9-tetrahydrocannabinol (THC), the main psychoactive component of Cannabis sativa L., have shown efficacy as antiemetics. Here, we report the case of Michael Roberts (MR), who we believe is the first British patient reimbursed by the National Health Service (NHS) England for the cost of medicinal cannabis flowers to manage CINV. Medical data were obtained from NHS records and individual funding request (IFR) forms. Patient-reported outcome measures (PROMs) were collected using validated questionnaires as part of the standard of care at the specialized private clinics where the prescription of medicinal cannabis was initiated. The patient presented with rectosigmoid adenocarcinoma with lung metastases. He received FOLFIRI (folinic acid, fluorouracil, and irinotecan) chemotherapy and underwent an emergency Hartmann's procedure with subsequent second-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy and lung ablation. MR reported severe nausea and vomiting associated with the initial FOLFIRI treatment. Antiemetics metoclopramide and aprepitant demonstrated moderated efficacy. Antiemetics ondansetron, levomepromazine, and nabilone were associated with intolerable side effects. Inhalation of THC-predominant cannabis flowers in association with standard medication improved CINV, anxiety, sleep quality, appetite, overall mood, and quality of life. Our results add to the available evidence suggesting that medicinal cannabis flowers may offer valuable support in cancer palliative care integrated with standard-of-care oncology treatment. The successful individual funding request in this case demonstrates a pathway for other patients to gain access to these treatments, advocating for broader awareness and integration of cannabis-based medicinal products in national healthcare services.

Gene polymorphisms of TACR1 serve as the potential pharmacogenetic predictors of response to the neurokinin-1 receptor antagonist-based antiemetic regimens: a candidate-gene association study in breast cancer patients.

PURPOSE: The current candidate gene association study aims to investigate tag SNPs from the TACR1 gene as pharmacogenetic predictors of response to the antiemetic guidelines-recommended, NK-1 receptor antagonist-based, triple antiemetic regimens. METHODS: A set of eighteen tag SNPs of TACR1 were genotyped in breast cancer patients receiving anthracycline and cyclophosphamide (with/without docetaxel) applying real-time PCR-HRMA. Data analysis for 121 ultimately enrolled patients was initiated by defining haplotype blocks using PHASE v.2.1. The association of each tag SNP and haplotype alleles with failure to achieve the defined antiemetic regimen efficacy endpoints was tested using PLINK (v.1.9 and v.1.07, respectively) based on the logistic regression, adjusting for the previously known chemotherapy-induced nausea and vomiting (CINV) prognostic factors. All reported p-values were corrected using the permutation test (n = 100,000). RESULTS: Four variants of rs881, rs17010730, rs727156, and rs3755462, as well as haplotypes containing the mentioned variants, were significantly associated with failure to achieve at least one of the defined efficacy endpoints. Variant annotation via in-silico studies revealed that the non-seed sequence variant, rs881, is located in the miRNA (hsa-miR-613) binding site. The other three variants or a variant in complete linkage disequilibrium with them overlap a region of high H3K9ac-promoter-like signature or regions of high enhancer-like signature in the brain or gastrointestinal tissue. CONCLUSION: Playing an essential role in regulating TACR1 expression, gene polymorphisms of TACR1 serve as the potential pharmacogenetic predictors of response to the NK-1 receptor antagonist-based, triple antiemetic regimens. If clinically approved, modifying the NK-1 receptor antagonist dose leads to better management of CINV in risk-allele carriers.

Comparison of oral aprepitant and intravenous fosaprepitant for prevention of chemotherapy-induced nausea and vomiting in pediatric oncology patients: a randomized phase III trial.

Background: Neurokinin-1 receptor antagonists have improved the management of chemotherapy-induced nausea and vomiting (CINV), but to date there has been no prospective comparison between oral aprepitant and intravenous fosaprepitant in pediatric oncology patients. Methods: Our study was a double-parallel study, and the distribution ratio was 1:1. Children aged 2-12 years who were undergoing moderate or highly emetogenic chemotherapy (MEC or HEC) were randomly assigned to receive ondansetron and dexamethasone combined with either a single dose of intravenous fosaprepitant (arm A), or 3 days of oral aprepitant (arm B). The primary outcome measure was the rate of complete response (CR) of CINV within the acute phase, defined as from the start through 24 hours after the last chemotherapy dose. Response during the delayed phase, overall response, and use of rescue antiemetics were also assessed. Results: We prospectively evaluated 108 eligible patients, including 55 receiving fosaprepitant. Study observations were made during a single cycle for each patient. The occurrence of CR in the acute phase was statistically higher for patients receiving fosaprepitant (95% vs. 79%, P=0.018<0.05). Modest differences were seen in CR rates during the delayed phase (71% vs. 66%, P=0.586), and overall response rate (69% vs. 57%, P=0.179). The use of antiemetic rescue medicines was similar between arms A (11%) and B (7%). Conclusions: Fosaprepitant produced more CRs of CINV in the acute phase than did aprepitant, although there were no statistical differences in delayed phase response, overall response, or use of rescue antiemetics. This study confirms the safety, efficacy, and potential advantages of fosaprepitant in reducing CINV in pediatric oncology patients. Trial Registration: ClinicalTrials.gov identifier: NCT04873284.

Adherence to antiemetic guidelines in solid cancer patients receiving highly emetogenic chemotherapy in Korea.

BACKGROUND: Highly emetogenic chemotherapy (HEC) is known to induce nausea and vomiting (CINV) in approximately 90% of cancer patients undergoing this regimen unless proper prophylactic antiemetics are administered. This study aimed to analyze the use of a three-drug prophylactic antiemetic regimen during the first cycle of chemotherapy and assess the compliance rate with the National Comprehensive Cancer Network (NCCN) guidelines. METHODS: This retrospective study utilized data from the National Inpatient Sample database from 2016 to 2020 provided by the Health Insurance Review and Assessment Service. The claims data encompassed 10 to 13% of inpatients admitted at least once each year. Patients with solid cancers treated with two HEC regimens, namely anthracycline + cyclophosphamide (AC) and cisplatin-based regimens, were selected as the study population. We evaluated the use of a three-drug prophylactic antiemetic regimen, including a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone and compliance with the NCCN guidelines. Multiple logistic regression was conducted to estimate the influence of variables on guideline adherence. RESULTS: A total of 3119 patients were included in the analysis. The overall compliance rate with the NCCN guidelines for prophylactic antiemetics was 74.3%, with higher rates observed in the AC group (87.9%) and lower rates in the cisplatin group (60.4%). The AC group had a 6.37 times higher likelihood of receiving guideline-adherent antiemetics than the cisplatin group. Further analysis revealed that, compared to 2016, the probability of complying with the guidelines in 2019 and 2020 was 0.72 times and 0.76 times lower, respectively. CONCLUSION: This study showed that a considerable proportion of HEC-treated patients received guideline-adherent antiemetic therapies. However, given the variations in adherence rates between different chemotherapy regimens (AC vs. cisplatin), efforts to improve adherence and optimize antiemetic treatment remain essential for providing the best possible care for patients experiencing CINV.

Chemotherapy induced nausea and vomiting may cause anxiety and depression in the family caregivers of patients with cancer.

Objective: To investigate the impact of chemotherapy induced nausea and vomiting (CINV) on the anxiety and depression of the primary family caregivers of patients with cancer. Methods: This study screened family caregivers of patients with cancer undergoing highly emetogenic chemotherapy (HEC) containing a 3-day cisplatin regime. Caregivers who did not experience anxiety or depression at baseline screening were enrolled in this study. Based on the patients' CINV status during chemotherapy, their family caregivers were divided into two groups: patients who experienced CINV (CINV group) and patients who did not experience CINV (No-CINV group). All enrolled family caregivers completed the Hospital Anxiety and Depression Scale (HADS) questionnaire on the fourth and 8 days of chemotherapy. Results: A total of 256 family caregivers were screened for this study, of which 195 caregivers without anxiety or depression at baseline were included. A total of 150 (76.9%) patients undergoing chemotherapy experienced acute CINV; 63 (42%) of their family caregivers experienced anxiety, and 65 (43.3%) developed depression. This was significantly higher than the experiences of the No-CINV group (2.2%, P < 0.001; 0%, P < 0.001, respectively). Among the patients undergoing chemotherapy, 86 (44.1%) experienced delayed CINV. The incidence of anxiety and depression in the family caregivers of patients with delayed CINV were 27.9 and 36%, respectively, both of which were significantly higher than that in the family caregivers of the No-CINV group (0.9%, P < 0.001; and 0.9%, P < 0.001, respectively). Conclusion: Acute and delayed CINV occurring in patients during chemotherapy may induce anxiety and depression in their family caregivers.

Retrospective Evaluation of a Dexamethasone Sparing Antiemetic Regimen: An Antiemetic Prophylaxis Study on NEPA (Netupitant Plus Palonosetron) for Preventing Chemotherapy-Induced Nausea and Vomiting (CINV) in Cancer Patients.

Background Corticosteroids, specifically dexamethasone (DEX), have been extensively utilized for the prevention of chemotherapy-induced nausea and vomiting (CINV). However, their usage is associated with a range of adverse events. In contrast, the combination of Netupitant Plus Palonosetron (NEPA) with a single dose of DEX provides comparable efficacy in preventing CINV over a five-day period following chemotherapy administration. This regimen offers the advantage of reducing the need for additional doses of DEX, particularly in the high-risk setting of HEC (Highly emetic chemotherapy). Objective To evaluate dexamethasone sparing anti-emetic regimen (single dose dexamethasone with NEPA) for prophylaxis of CINV in patients receiving HEC. Methodology This is a retrospective, observational, real-world, single-center study including data of 69 patients who received high-dose emetogenic chemotherapy and were administered DEX (8 or 12 mg) on day 1, with no dose of DEX on days 2, 3, and 4, combined with an oral combination of tablet netupitant 300 mg and palonosetron 0.5 mg. NEPA was taken orally an hour prior to the start of the HEC cycle. The primary efficacy endpoint was complete response (CR) which is defined as no nausea, emesis, or no rescue medication during the Acute (< 24 hours) and Delayed Phase (25-120 hours) of chemotherapy. Results The overall CR achieved in the acute and delayed phase for vomiting is 100% at all four follow-ups. The CR achieved in the acute phase is 95.7% whereas 98.6% of patients showed CR in the delayed phase respectively. No patient required any rescue medication. No acute and delayed phase of vomiting was reported. Conclusion A simplified regimen of NEPA plus single-dose DEX offers effective CINV prevention throughout five days post-chemotherapy with the advantage of sparing patients additional doses of DEX in the high-emetic-risk setting chemotherapy.

Megestrol acetate dispersible tablets with a 5-HT3 receptor antagonist and dexamethasone vs. 5-HT3 receptor antagonist plus dexamethasone, can better control chemotherapy-induced nausea and vomiting: a randomized controlled study.

Background: A reasonable and effective control of chemotherapy-induced nausea and vomiting (CINV) plays an important role in the comprehensive treatment of cancer. Megestrol belongs to the 17α-hydroxyprogesterone derivative and is a highly effective synthetic progesterone. Recorded in the instructions may improve appetite and cachexia in patients with advanced tumors. In recent years, clinical practice and small sample studies have shown that megestrol combined with chemotherapy can improve CINV. This randomized controlled trial aimed to evaluate the clinical efficacy and safety of megestrol acetate combined with a 5-Hydroxytryptamine (5-HT3) receptor antagonist and dexamethasone in patients with CINV. Methods: Patients with malignant tumors who were treated with cisplatin-containing chemotherapy in our hospital from September 2018 to December 2019 were enrolled. A total of 120 patients were selected and randomly assigned to receive either megestrol acetate dispersible tablets with a 5-HT3 receptor antagonist and dexamethasone (megestrol group) or a 5-HT3 receptor antagonist plus dexamethasone (control group). Megestrol acetate dispersible tablets: 160 mg orally every morning from the day of chemotherapy until it lasts for ten days. Abstract IV of the quality-of-life scale for cancer patients in China was used to assess the quality of life (QOL) of the participants. All adverse reactions during chemotherapy were assessed according to the CTCAE 4.03 evaluation standard issued by the National Cancer Institute and divided into five grades according to severity. Results: For the control of nausea, the rates of complete prevention were significantly higher in the megestrol group than in the control patients during the delayed [53.3% (31/60) vs. 30.0% (18/60), P=0.012] and overall [40.0% (24/60) vs. 15.0% (9/60), P=0.002] observation periods. Moreover, the megestrol combination treatment group also achieved markedly higher rates of complete remission of vomiting than the control group during the delayed observation period [76.7% (46/60) vs. 51.7% (31/60), P=0.001], achieving an overall higher proportion of remission during the study period [68.3% (41/60) vs. 46.6% (28/60), P=0.0016]. Conclusions: The triple antiemetic protocol using megestrol acetate with a 5-HT3 receptor antagonist plus dexamethasone can improve CINV symptoms caused by highly emetogenic chemotherapy (HEC) with cisplatin, with an excellent control effect and few adverse reactions, especially for delayed CINV. Trial Registration: Chinese Clinical Trial Registry ChiCTR1800017953.

Dietary strategies for chemotherapy-induced nausea and vomiting: A systematic review.

BACKGROUND & AIMS: Chemotherapy-induced nausea and vomiting (CINV) is one of the most distressing cancer treatment side effects, affecting 20-70% of patients despite routine antiemetic prescription. Although dietary modifications are routinely recommended in clinical practice, there is lack of data synthesis to determine which dietary strategies for managing CINV are supported by quality evidence. This systematic review was conducted to examine the effect of dietary strategies on incidence and severity of CINV in adults compared with no intervention, usual care, or alternative strategies. METHODS: Five electronic databases were searched from inception to 15th July 2021 for original research studies of interventional or observational design assessing dietary strategies for CINV. The quality of evidence was appraised, data were synthesized narratively, and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment of the certainty of the evidence was applied. RESULTS: Twenty-one studies were included, 10 (48%) interventional studies and 11 (52%) observational studies. Most interventional and observational studies had a high or neutral risk of bias (70% and 72%, respectively). Of the interventions studied, strongest evidence with highest certainty was found for the very large positive effect of CINV-specific education and support with a personalized meal plan from a dietician, implemented in person or in writing, for reducing the severity of nausea and overall CINV (effect size: very large; GRADE: high). A statistically significant very large positive effect of ginger tea consumption was also found on overall CINV severity; however, certainty in this effect was very low. Although confidence in the findings from observational studies was very low to low, a statistically significant positive association was also found between a moderate intake of alcohol and incidence of nausea, vomiting, or overall CINV as well as nausea severity; the Mediterranean diet and nausea incidence and severity; and adequate intake of energy, protein, fat, or carbohydrate and nausea or vomiting incidence. CONCLUSION: Improved CINV was associated with CINV-specific nutrition education and support from health professionals. Non-restrictive dietary patterns that include adequate energy and macronutrient intakes, particularly protein, and include ginger, and Mediterranean diet concepts may benefit CINV; however, the confidence in the body of evidence to inform these conclusions is mostly very low to moderate. Future rigorous trials with adequate sample sizes, clearly defined dietary strategies, and valid outcome measures are warranted prior to dietary strategies being routinely prescribed alongside antiemetic regimens.

Evaluating the impact of chemotherapy-induced nausea and vomiting on daily functioning in patients receiving dexamethasone-sparing antiemetic regimens with NEPA (netupitant/palonosetron) in the cisplatin setting: results from a randomized phase 3 study.

BACKGROUND: The non-inferiority of dexamethasone (DEX) on day 1, with or without low-dose DEX on days 2 and 3, combined with oral NEPA (netupitant/palonosetron), compared with the guideline-consistent use of DEX was demonstrated in cisplatin. Here, we complete the analysis by assessing the impact of emesis on daily lives of patients receiving DEX-sparing regimens using the Functional Living Index-Emesis (FLIE). METHODS: Chemotherapy-naïve patients undergoing cisplatin (≥70 mg/m2), were given NEPA and DEX (12 mg) on day 1 and randomized to receive either 1) no further DEX (DEX1), 2) oral DEX (4 mg daily) on days 2-3 (DEX3), or 3) DEX (4 mg twice daily) on days 2-4 (DEX4; control). Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included the FLIE nausea domain, vomiting domain, and overall combined domain scores, as well as the proportion of patients with no impact on daily life (NIDL; overall score > 108). This was a protocol-planned analysis. RESULTS: In the DEX1 group, no significant differences were observed in the FLIE nausea score (48.9 [±1.8; SE] vs. 53.7 [±1.5]), vomiting score (56.6 [±1.4] vs. 58.7 [±0.8]) and overall score (105.6 [±2.8] vs.112.4 [±1.9]) versus DEX4 control; similar results were observed in the DEX3 group for nausea score (49.6 [±1.7]), vomiting score (58.2 [±1]) and overall score (107.8 [±2.4]) versus control. There were no significant between-group differences in the proportion of patients reporting NIDL. CONCLUSION: Reducing DEX, when administered with NEPA, does not seem to adversely impact the daily functioning in patients undergoing cisplatin. TRIAL REGISTRATION: ClinicalTrials.gov NCT04201769 . Registration date: 17/12/2019 - Retrospectively registered.

Olanzapine enhances the effect of conventional drugs in chemotherapy inducing nausea and vomiting: A randomized clinical trial.

Background: Chemotherapy inducing nausea and vomiting (CINV) is one of the significant side effects of anti-cancer treatment, and its full prevention is a potential challenge. This study was done to specify the effect of olanzapine in this setting. Methods: In this randomized, double-blind, clinical trial study, olanzapine was compared with a placebo in combination with dexamethasone and granisetrone in patients with cancer. Patients in the intervention group received dexamethasone , granisetron and olanzapine. Patients in the control group received a placebo instead of olanzapine. Overall, acute nausea and vomiting prevention were the primary and secondary end points; complete response (no nausea,no vomiting) in the delayed period of chemotherapy was the third end point. Response to treatment was evaluated by the Functional Living Index Emesis (FLIE) questionnaire completion in the first, the third and the fifth of chemotherapy. Results: Percentage reduction in mean±SD nausea and vomiting in the overall phase (0-120 hours) of intervention group compared to the control group respectively were 29.94±2.06, 69.75±2.32 [(57.93% reduction (p<0.001)]. For the acute phase (0-24 hours) were 26.08±2.36, 51.85±2.24 [(47.21% reduction (p<0.001)], for the delayed phase (24-120 hours), were 31.26±2.57, 67.91±2.12 ,[(55.11% reduction;(p<0.001)] respectively. Conclusion: Olanzapine, along with dexamethasone and granisetron, significantly reduced vomiting and nausea in patients undergoing chemotherapy. No adverse event of olanzapine was observed in the patients.

Netupitant-palonosetron (NEPA) for Preventing Chemotherapy-induced Nausea and Vomiting: From Clinical Trials to Daily Practice.

Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event associated with many anticancer therapies and can negatively impact patients' quality of life and potentially limit the effectiveness of chemotherapy. Currently, CINV can be prevented in most patients with guideline-recommended antiemetic regimens. However, clinicians do not always follow guidelines, and patients often face difficulties adhering to their prescribed treatments. Therefore, approaches to increase guideline adherence need to be implemented. NEPA is the first and only fixed combination antiemetic, composed of netupitant (oral)/fosnetupitant (intravenous) and palonosetron, which, together with dexamethasone, constitute a triple antiemetic combination recommended for the prevention of CINV for patients receiving highly emetogenic chemotherapy and for certain patients receiving moderately emetogenic chemotherapy. Thus, NEPA offers a convenient and straightforward antiemetic treatment that could improve adherence to guidelines. This review provides an overview of CINV, evaluates the accumulated evidence of NEPA's antiemetic activity and safety from clinical trials and real-world practice, and examines the preliminary evidence of antiemetic control with NEPA in daily clinical settings beyond those described in pivotal trials. Moreover, we review the utility of NEPA in controlling nausea and preserving patients' quality of life during chemotherapy, two major concerns in managing patients with cancer.

Complementary and alternative medicine modalities used to treat adverse effects of anti-cancer treatment among children and young adults: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Dealing with the symptom burden of cancer diagnosis and treatment has led parents to seek different self-management strategies including Alternative and Complementary Medicine (CAM). The aim of this study was to perform a systematic review and meta-analysis about the use and effect of CAM modalities to treat adverse effects of conventional cancer treatment among children and young adults. METHODS: Six scientific research databases were used to identify randomized controlled trials (RCTs) from 1990 to September 2020. Included studies investigated the use of CAM to treat cancer treatment related adverse effects in children and young adults compared to controls. RESULTS: Twenty RCTs comprising 1,069 participants were included in this review. The included studies investigated acupuncture, mind-body therapies, supplements, and vitamins for chemotherapy-induced nausea and vomiting (CINV), oral mucositis, and anxiety among children and young adults who underwent conventional cancer treatment. Seven studies (315 participants) were included in the meta-analysis. The overall effect of CAM (including acupuncture and hypnosis only) on chemotherapy-induced nausea and/or vomiting and controls was statistically significant with a standard mean difference of -0.54, 95% CI [-0.77, -0.31] I2 = 0% (p < 0.00001). There was a significant difference between acupuncture and controls (n = 5) for intensity and/or episodes of CINV with an SMD -0.59, 95% CI [-0.85, -0.33] (p < 0.00001). No significant difference was found between hypnosis and controls (n = 2) for severity or episodes of CINV with an SMD -0.41, 95% CI [-1.09, 0.27] I2 = 41% (p = 0.19). CONCLUSION: Current evidence from this meta-analysis of randomized controlled trials shows that CAM, including acupuncture and hypnosis only, is effective in reducing chemotherapy-induced nausea and vomiting in children and young adults. More rigorous trials and long-term effects should be investigated if acupuncture and hypnosis are to be recommended for clinical use.

Mechanisms of Chemotherapy-Induced Neurotoxicity.

Since the first clinical trials conducted after World War II, chemotherapeutic drugs have been extensively used in the clinic as the main cancer treatment either alone or as an adjuvant therapy before and after surgery. Although the use of chemotherapeutic drugs improved the survival of cancer patients, these drugs are notorious for causing many severe side effects that significantly reduce the efficacy of anti-cancer treatment and patients' quality of life. Many widely used chemotherapy drugs including platinum-based agents, taxanes, vinca alkaloids, proteasome inhibitors, and thalidomide analogs may cause direct and indirect neurotoxicity. In this review we discuss the main effects of chemotherapy on the peripheral and central nervous systems, including neuropathic pain, chemobrain, enteric neuropathy, as well as nausea and emesis. Understanding mechanisms involved in chemotherapy-induced neurotoxicity is crucial for the development of drugs that can protect the nervous system, reduce symptoms experienced by millions of patients, and improve the outcome of the treatment and patients' quality of life.

Netupitant/palonosetron without dexamethasone for preventing nausea and vomiting in patients with multiple myeloma receiving high-dose melphalan for autologous stem cell transplantation: a single-center experience.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent adverse events compromising quality of life (QoL) in patients undergoing autologous stem cell transplantation (ASCT). However, CINV prophylaxis is still lacking uniformity for high-dose melphalan (HDM), which is used to condition patients with multiple myeloma (MM). Netupitant/palonosetron (NEPA) is administered with dexamethasone (DEXA) for CINV prevention in several chemotherapy regimens. Our study aims to assess the efficacy of NEPA, without DEXA, in preventing CINV in 106 adult patients with MM receiving HDM and ASCT. All patients had antiemetic prophylaxis with multiple doses of NEPA 1 h before the start of conditioning and after 72 h and 120 h. A complete response (CR) was observed in 99 (93%) patients at 120 h (overall phase). The percentage of patients with complete control was 93%. The CR rate during the acute phase was 94% (n = 100). During the delayed phase, the CR rate was 95% (n = 101). Grade 1 nausea and vomiting were experienced by 82% and 12% of the patients, respectively. Grade 2 nausea was reported in 18% and vomiting in 10% of patients. Our results showed, for the first time, that NEPA, without DEXA, was a well-tolerated and effective antiemetic option for MM patients receiving HDM followed by ASCT.

Implementation of a clinical pharmacist-led service to optimize management of refractory chemotherapy-induced nausea and vomiting in adult hematology/oncology clinic.

OBJECTIVE: Chemotherapy-induced nausea and vomiting (CINV) is a common and potentially debilitating adverse effect of chemotherapy. Refractory CINV can be particularly difficult to control. This report provides details on the implementation and evaluation of a pharmacist-led program for the management of refractory CINV in hematology and oncology clinics. METHODS: A pharmacist-led program open to adult outpatients with refractory CINV was implemented at University of Wisconsin. Pharmacists conducted baseline and follow-up assessments, provided patient education, and started, discontinued, and/or adjusted antiemetics as clinically necessary for all enrolled patients. Retrospective chart review was used to describe the proportion of patients whose CINV improved through pharmacist intervention, effect of the program on antiemetic adherence, categorization of pharmacist interventions, and duration of patient enrollment. RESULTS: Forty-six patients were enrolled between February 2019 and January 2020. Forty-one patients (89.1%) had an overall reduction in their nausea and vomiting from baseline. Eleven patients (23.9%) met criteria for nonadherence to prescribed antiemetics at baseline; all patients were adherent at unenrollment. A total of 111 pharmacist interventions were made. The most common intervention was addition of new breakthrough antiemetic. The least common intervention was dose escalation of a previously prescribed antiemetic. The average number of interventions made per patient was 2.5. On average, patients were enrolled in the program for 16.6 days and met with a pharmacist three times. CONCLUSION: Implementation of this program standardized and streamlined pharmacist involvement with refractory CINV. Enrollment resulted in a measurable reduction in nausea and/or vomiting for patients with refractory CINV.

Is area under the curve the best parameter for carboplatin induced emetic risk stratification?

Carboplatin (CBDCA)-induced emetic risk is currently classified on the basis of CBDCA-area under the curve (CBDCA-AUC). We investigated the utility of three CBDCA dosage parameters for predicting emesis by CBDCA. Patients with thoracic cancer treated with CBDCA were included. The endpoints were complete response (CR) and total control (TC). CR was defined as no vomiting and no use of rescue medication during the overall assessment period, whereas TC was defined as no vomiting, nausea, nor use of rescue medication during the overall assessment period. The parameters of CBDCA were defined as follows: (1) CBDCA-AUC; (2) CBDCA/body surface area (BSA): the administered dose of CBDCA per body surface area (mg/m2); and (3) total CBDCA/body: the total administered dose of CBDCA (mg). Eighty-five patients were evaluated. The median CBDCA/BSA but not CBDCA-AUC was higher in patients with non-CR compared to those with CR. Receiver operating characteristic curve analysis revealed that the AUC of CBDCA/BSA for predicting non-CR was higher than that of CBDCA-AUC. CBDCA/BSA shows greater potential for predicting CBDCA-induced emetic risk compared with CBDCA-AUC, which is the parameter in current antiemetic guidelines.

Medical Cannabis as Adjunctive Therapy for Head and Neck Cancer Patients.

The goal of this systematic review was to define a consensus within the current literature regarding the impact/effect of cannabis or cannabinoids on the treatment of patients with head and neck cancer. We conducted a review of PubMed, Embase, and Web of Science databases, using a comprehensive search strategy, focusing on articles relating to head & neck cancer and cannabis/cannabinoids without a time limit for publication. Two, independent reviewers screened articles based on title/abstract and included the ones selected by both. We then conducted a full-text review and excluded all articles which did not meet inclusion criteria. A single reviewer then assessed studies for methodological quality and extracted relevant data using a premade data collection tool. We identified five studies that met inclusion criteria. Studies were of varying quality and the majority investigated recreational cannabis use with only one study reporting dosing across participants. Lack of standardized cannabis exposure presents a wide array of potential confounding variables across the remaining studies. Meta-analysis was not attempted due to variability in reported outcomes. It is impossible to draw any conclusions regarding the benefit or adverse effects of current medical cannabis products in this patient population. The literature regarding the effect of cannabis/cannabinoids on head & neck cancer patients is limited. However, the current lack of evidence does not definitively disprove the efficacy of cannabis. High-quality studies are necessary for physicians to provide advice to patients who are either using or interested in cannabis as an adjunctive treatment.

Nomogram for Predicting Chemotherapy-Induced Nausea and Vomiting for Breast Cancer Patients.

Chemotherapy-induced nausea and vomiting (CINV) is a common side effect of cancer treatment. The factors influencing CINV in breast cancer patients remain unclear. In this study, we developed a nomogram for predicting the occurrence of CINV in this group using prospective clinical data. We pooled data from multiple studies which focused on the emetogenic chemotherapy. Then, we collected 334 breast cancer patients at Hunan Cancer Hospital (training set) to analyze the demographic and clinical variables. Using multivariate logistic regression, we identified the five significant factors that were associated with CINV: history of CINV, chemotherapy regimen, chemotherapy cycle, metastasis, and symptoms of distress. Then, we construct a prediction nomogram. The external validation set comprised an additional 66 patients. The reliability of the nomogram was assessed by bootstrap resampling. The C-index was 0.78 (95% confidence interval [CI], 0.73-0.85) for the training set and 0.74 (95% CI, 0.62-0.85) for the validation set. Calibration curves showed good concordance between predicted and actual occurrence of CINV. In conclusions, our nomogram model can reliably predict the occurrence of CINV in breast cancer patients based on five significant variables, which might be useful in clinical decision-making.

Single daily dosing versus divided dosing intravenous ondansetron to prevent chemotherapy-induced nausea and vomiting among children: A comparative randomized double-blind controlled trial.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is a common complication in cancer treatment. Ondansetron is an effective antiemetic drug widely used to prevent CINV; however, the effective administrative dosing strategies among pediatrics remain unclear. The study aimed to investigate clinical effectiveness of single daily dosing versus divided dosing ondansetron. METHODS: In all, 194 children undergoing chemotherapy were randomized to receive either single daily dosing (0.3 mg/kg/dose) or divided dosing (0.15 mg/kg/dose every 8 hours) intravenous ondansetron for 24 hours. Clinical parameters including number of emesis episodes, nausea scores, appetite levels, parent's satisfaction, and adverse effects within 24 hours were analyzed. RESULTS: No significant differences were found between the two dosing strategies concerning number of emesis episodes and parent's satisfaction. However, nonleukemic hematologic malignancies and concurrent administration of intrathecal methotrexate-hydrocortisone-cytarabine (IT-MHA) were associated with increased risk of acute-phase vomiting. Interestingly, none of the patients aged under 7 years, receiving divided dosing ondansetron, presented nausea symptoms compared with those receiving single daily dosing (p-value .034). No significant differences regarding headache were observed between the two dosing strategies and none of the patients experienced QTc prolongation. CONCLUSION: Ondansetron administered as divided dosing should be considered among children aged under 7 years to prevent chemotherapy-induced nausea and among patients receiving low emetogenic chemotherapy to maintain their appetite. Both administrative dosing strategies were well tolerated with no significant adverse effects.