Phases Of Chemotherapy-induced Nausea And Vomiting Research Articles

Prevention of CINV in Patients with Multiple Myeloma or Lymphoma Undergoing Hematopoietic Stem Cell Transplantation: NEPA Versus Ondansetron. a Monocentric Real-Life Experience

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) are adverse events that compromise quality of life and treatment compliance in patients undergoing autologous hematopoietic stem cell transplantation (ASCT). Polychemotherapy regimens, used as conditioning regimens for ASCT in lymphomas, and high-dose melphalan (≥140 mg/mq), used in multiple myeloma (MM), have high emetogenic risk. Control of CINV is difficult and there is no uniformity for its prophylaxis. Antiemetic guidelines recommend, for prophylaxis, co-administration of a triplet regimen of a serotonine (5-HT3) receptor antagonist (RA), as Ondansetron, a neurokinin-1 RA, and dexamethasone. Netupitant-Palonosetron (NEPA), an oral formulation derived from the combination of Netupitant (NK1-RA) and Palonsetron, has been approved as prophylaxis of CINV but its experience in the stem cell transplant setting is still limited. AIMS: The primary aim of this study was to compare the efficacy of Ondansetron versus NEPA in terms of reduction of CINV in patients affected by lymphoma or MM who undergone ASCT. The secondary aims included comparing the duration of CINV, based on the use of Ondansetron or NEPA, and their safety profile in terms of reduction of extrahaematological toxicity (as mucositis or diarrhea). METHODS: In this retrospective monocentric study, we enrolled 76 patients (48 with MM and 28 with lymphoma), who underwent ASCT between March 2021 and March 2022. All patients with MM received high dose of melphalan, those with lymphoma received FEAM. Regarding antiemetics patients were divided according to whether they received NEPA or Ondansetron .Patients' characteristics are in Table 1. RESULTS: Among all, fifty patients (65%) reported CINV of any grade. In particular, the group experiencing CINV included about half of patients treated with NEPA (56%) and almost all those treated with Ondansetron (91%). Among the 26 patients who didn't report CINV (35%), the majority received NEPA (92%) (P = 0.0032)(Fig. 1a). Focusing on patients with MM, 33 experienced CINV (68%), and they were 59% of MM patients treated with NEPA and 93% of those treated with Ondansetron. Fifteen patients did not experience CINV (32%) and almost all of them (93%) had been treated with NEPA (P = 0.037)(Fig. 1b). Sixty-one percent of the 28 patients with lymphoma reported CINV (P= 0.1914) (Fig. 1c). Mean duration of CINV was significantly shorter for patients treated with NEPA than for those treated with Ondansetron (4.8 days vs 9.2 days) (P= 0.002) (Fig. 1d). Regarding extraematological toxicity of chemotherapy, as mucositis and diarrhea, we didn't find any significant difference between the two groups of patients. Regarding the outcome to NEPA, complete response rate (no emesis, no rescue medication) was 37% during overall phases of CINV, 28% of patients had complete control (complete response with no more than mild nausea) and 31% had uncontrolled nausea. Conversely, in the Ondansetron group, only 5% of patients had complete response and 95% had uncontrolled nausea (Fig. 1e). All patients with uncontrolled nausea required a rescue therapy. According to CTCAE, 69% of patients receiving NEPA had grade 1 nausea and 6% had none, while all patients receiving Ondansetron had CINV and 85% of them had grade 2 nausea. CONCLUSIONS: In our experience, NEPA has shown superiority in the prevention of CINV, in highly emetogenic regimens in both patients with myeloma or lymphoma, with advantages on the severity and the duration of CINV. Given the high burden of CINV in the whole population analyzed in the study, regardless of the antiemetic used, it would be useful to identify patients at greatest risk and standardize CINV prophylaxis and treatment protocols depending on the different chemotherapy regimens and their emetogenic risk.

Management of Chemotherapy-Induced Nausea and Vomitting in Breast Cancer Patients: A Prospective Cohort Study

Through a prospective cohort study we aimed to optimize prevention and management of chemotherapy-induced nausea and vomiting (CINV) in the emergence of new therapies for breast cancer patients. We included breast cancer patients treated with moderate emetogenic (MEC) or highly emetogenic chemotherapy (HEC) all stages combined, from April 2021 to November 2021. Patients were required to answer a survey of 32 questions in order to analyze the potential involvement of known and unknown risk factors in the occurrence of CINV. The acute phase of CINV was defined as nausea and vomiting that developed ≤ 24 hours after the start of chemotherapy. Delayed phase of CINV was defined as nausea and vomiting that developed > 24 hours after the start of chemotherapy. The severity of nausea and vomiting was evaluated with common terminology criteria for adverse events (CTCAE) v5.0; publish to date: November 27, 2017. Analysis and results were performed using JAMOVI statistical software. In total, 177 patients received chemotherapy, 103 patients(58%) received (HEC), and 74 patients (42%) received (MEC). All patients were female (100%). Risk factors associated to occurrence of CINV included previously known factors: Younger age than 50 years (29,8%), history of pregnancy-related nausea and vomiting (74,7%), alcohol use (no patient reported previous alcohol consumption), failure to adhere to antiemetic treatment guidelines (9,6%). The compliance with treatment score (90,4%) showed a good commitment of the patients in the process of their medical healthcare. Other potential risk factors have been also explored to determine their involvement or not in the occurrence of CINV (cancer stage, performance status, education level, chemotherapy protocols, the use of traditional herbs known as an antibacterial agent and immunity booster in our context). In the acute phase, (78%) of patients experienced nausea and (47,8%) experienced vomiting. In the delayed phase, (37,1%) of patients experienced nausea and only (15,3%) experienced vomiting. The severity of nausea and vomiting was evaluated according to CTCAE v5.0 in both groups HEC and MEC. Only (8,7%) had to stop treatment for non-tolerance (table 1-2). The present study demonstrated that high compliance to treatment guidelines for CINV and individualized care could lead to more optimal management of CINV.

The Effectiveness of an Oral Fixed-Dose Combination of Netupitant and Palonosetron (NEPA) in Patients With Multiple Risk Factors for Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Observational Indian Study.

BackgroundFemale gender, young age, first chemotherapy cycle, and low alcohol intake have all been linked to an increased risk of nausea and vomiting from chemotherapy. We intended to see if netupitant and palonosetron (NEPA) could prevent chemotherapy-induced nausea and vomiting (CINV) in patients with risk factors such as age, gender, chemotherapy cycle number, and alcohol consumption history.MethodsIn this retrospective study, chemotherapy-naïve patients who were prescribed netupitant (300 mg) and palonosetron (0.50 mg) (NEPA) before the first cycle of chemotherapy were analyzed for overall, acute, and delayed phases of complete response (CR), complete protection (CP), and control.ResultsIn the acute phase (AP), delayed phase (DP), and overall phase (OP), complete response was 88.23%, 86.27%, and 86.27%, respectively; complete protection was 80.39%, 78.43%, and 76.47%, respectively; and complete control was 76.47%, 72.54%, and 70.58%, respectively, in the whole population (i.e., 51 patients). Complete response, protection, and control in the overall phase were achieved by 86.27%, 72.72%, and 68.18% of patients who received the highly emetogenic chemotherapy (HEC) regimen (i.e., 44 patients), respectively.ConclusionNEPA provided a consistent magnitude of benefit for patients who are at high risk, receiving HEC and moderately emetogenic chemotherapy (MEC), and having good control in the acute, delayed, and overall phases of CINV.

The Efficacy and Safety of Adding Olanzapine to Triple Drugs Regimen to Prevent Chemotherapy-induced Nausea and Vomiting: A systematic Review and Meta-analysis of RCTs

Chemotherapy-induced nausea and vomiting (CINV) is a complication of highly emetogenic chemotherapy (HEC) agents. The present meta-analysis was conducted to quantify and analyze the efficacy and safety of adding olanzapine to a Neurokinin Receptor Antagonist (NKRA) based triple-drug regimen in preventing HEC-induced CINV. Electronic database searches in PUBMED and Cochrane library was conducted using MeSH search terms “olanzapine” and “chemotherapy-induced nausea and vomiting.” Randomized or cross-over trials comparing the efficacy of “olanzapine + NKRA based triple-drug regimen” vs. “placebo + NKRA based triple-drug regimen” in patients of age > 18 years with any malignancy receiving HEC were considered under inclusion criteria. Complete Response (CR) for the delayed (25–120 h) phase of CINV in patients receiving HEC agents was the primary outcome measure analyzed. Outcome measures were estimated by calculating the Risk Difference (RD) values and their 95% Confidence Intervals (CI). The Mantel-Haenszel method and both fixed and random effect models were used in the analysis by Revman 5.4.1 soft- ware. An additional 14% (RD: 0.14, 95% CI: 0.09 to 0.19) of patients treated with olanzapine + triple-drug regimen had a statistically significant higher CR in the delayed phase when compared to placebo + NKRA-based triple-drug regimen. Adding olanzapine at 10mg to the triple-drug regimen significantly improves delayed phase CR rates by 16% and delayed phase ‘no significant nausea’ rates by 30%. Results need to be interpreted cautiously in the background of response variations and limited trials included in our analysis

Dexamethasone-sparing regimen is an effective and safe alternative in overall antiemetic protection: A systematic review and meta-analysis.

Objective:We performed a meta-analyisis to evaluate the efficacy of maintenance dexamethasone against acute or delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately or highly emetic risk chemotherapy regimen.Methods:PubMed, Embase, and Cochrane Library were searched for eligible studies. Data comparing maintenance dexamethasone with single-dose dexamethasone during the acute, delayed, and overall phase of CINV were extracted. Overall risk ratio (RR) was used to estimate the efficacy and adverse effects.Results:Nine studies were included. In delayed phase, maintenance dexamethasone has similar efficacy to single-dose dexamethasone for no emetic episodes (RR, 1.06; 95% confidence interval [CI], 1.00–1.14), complete response (RR, 1.04; 95% CI, 0.98–1.11), complete control (RR, 1.07; 95% CI, 0.98–1.16), and total control (RR, 1.06; 95% CI, 0.91–1.23). In overall phase, maintenance dexamethasone has similar efficacy to single-dose dexamethasone for no emetic episodes (RR, 1.02; 95% CI, 0.94–1.11), complete response (RR, 1.02; 95% CI, 0.95 -1.09), complete control (RR, 1.03; 95% CI, 0.94–1.13), total control (RR, 1.05; 95% CI, 0.90–1.23), and no rescue medication (RR, 1.07; 95% CI, 0.97–1.19). Maintenance dexamethasone was only superior to single-dose dexamethasone for no rescue medication during delayed phase (RR, 1.10; 95% CI, 1.01–1.21, P = .034). The incidence of hiccup was observed higher in maintenance dexamethasone group (RR = 3.16, 95% CI, 1.12–8.92).Conclusion:The single-dose dexamethasone regimen offers high and similar overall control of symptoms as the maintenance dexamethasone regimen in this population. Multiple-day dexamethasone was suitable for patients who used rescue medication during the delayed phase.

Granisetron in the treatment of chemotherapy-induced nausea and vomiting (CINV) – is there still a role after comparison with palonosetron?

ABSTRACTIntroduction: Chemotherapy-induced nausea and vomiting (CINV) has a negative impact on the lives of subjects receiving chemotherapy. In 2009, the second generation 5-HT3-receptor antagonist, palonosetron, which is longer-acting than granisetron, was shown, as part of dual therapy with dexamethasone, to be superior to intravenous granisetron in the delayed phase of CINV.Area covered: In an attempt to maintain plasma levels of granisetron during the delayed phase of CINV, longer-acting preparations of granisetron have been manufactured. In addition to comparing intravenous/oral granisetron with palonosetron, this review considers the new longer-acting preparations of granisetron (transdermal and subcutanous) with emphasis on whether they are effective in the delayed phase of CINV.Expert opinion: Comparison of intravenous/oral granisetron and palonosetron, as part of triple therapy against the delayed phase of CINV, do not give clear-cut results as to non-inferiority or superiority of either agent. Subcutaneous granisetron is more convenient to use than transdermal granisetron, and has been shown to be non-inferior to palonosetron, as part of dual therapy, in the treatment of the acute and delayed phases of CINV. At present, it seems likely that there will be ongoing roles for intravenous and subcutaneous granisetron in CINV, but further data is required to ascertain the future of transdermal granisetron.

Efficacy and safety of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis.

Olanzapine is an anti-psychotic drug that has been used for preventing and treating Chemotherapy-Induced Nausea and Vomiting (CINV). This study aimed to systematically review and meta-analyze the efficacy and safety of olanzapine for prophylaxis and treatment of CINV. We conducted a systematic literature search of MEDLINE, EMBASE, SCOPUS, and the Cochrane Central Register of Controlled Trials-CENTRAL up to July 15, 2016. All observational and intervention studies were included, but only the intervention studies were pooled for meta-analysis. The efficacy outcome was the proportion of patients achieving complete response (CR) - no emesis and no rescue therapy, in the acute, delayed, and overall phases. The safety outcomes were the adverse events associated with olanzapine according to Common Terminology Criteria for Adverse Events (CTCAE). Sixteen studies were eligible: 15 clinical trials and 1 observational study. Nine of the interventional studies were pooled for meta-analysis. The CR of olanzapine was superior to other anti-emetic regimens, in both the delayed and overall phases (RR=1.27, 95% CI 1.07-1.49, RR=1.32, 95% CI 1.08-1.62, respectively). However, olanzapine was not better than standard CINV prophylaxis of the nausea and emesis outcome in the acute phase. Drowsiness and constipation were the most reported adverse events. No grade 3 or 4 adverse events were reported. Olanzapine is effective and safe at reducing during the delayed and overall phase of the CINV prevention. Other regimens might be added, in cases of CINV during the acute phase of CINV.

Management of acute and delayed chemotherapy-induced nausea and vomiting: role of netupitant-palonosetron combination.

PurposeThe purpose of this review is to summarize and discuss the recently published data (both original studies and reviews) on the oral medication NEPA, consisting of netupitant (a neurokinin-1 receptor antagonist [NK1RA], 300 mg dose) and palonosetron (5-hydroxytryptamine [serotonin or 5HT] type 3 receptor antagonist [5HT3RA], 0.5 mg dose), in the prevention of the acute and delayed nausea and vomiting in patients receiving highly or moderately emetogenic chemotherapy.MethodsThis review was based on the very limited number of available published trials consisting of two Phase III studies and one Phase II dose-selecting trial.ResultsThese studies demonstrated some therapeutic benefits of NEPA over related chemotherapy-induced nausea and vomiting (CINV) prophylaxis management, as well as its beneficial safety profile. In particular, compared with single-dose 0.5 mg palonosetron, the complete response rates for all phases of CINV for the first cycle of highly emetogenic chemotherapy (with cisplatin), as well as anthracycline–cyclophosphamide-based moderately emetogenic chemotherapy, were significantly higher for single-dose NEPA. The high efficacy of NEPA in terms of prevention of CINV continued throughout repeated cycles of highly and moderately emetogenic therapies.ConclusionIt is currently recommended that patients who are administered highly emetogenic chemotherapy regimens should obtain a three-drug combination consisting of NK1RA, 5HT3RA, and dexamethasone. The recently available oral combination of NEPA plus dexamethasone provides an additional pharmacological management option that could be considered in this scenario.

Update on the management of chemotherapy-induced nausea and vomiting - focus on palonosetron.

PurposeNausea and vomiting are major adverse effects of chemotherapy and can greatly impact patients’ quality of life. Although chemotherapy-induced nausea and vomiting (CINV) prevalence is high, treatment remains difficult. Palonosetron is a 5-hydroxytryptamine receptor antagonist (5-HT3RA) approved for treatment of CINV. The purpose of this review is to discuss existing and emerging therapeutic options, and examine studies focusing on palonosetron with regards to efficacy, pharmacology, tolerability, safety, and patient-derived outcomes.MethodsA literature search was conducted using Ovid MEDLINE and EMBASE to identify relevant studies using palonosetron alone or in combination with other antiemetics. Studies were extracted if they included complete response (CR), complete control (CC), no nausea, no vomiting, and no rescue medications as an endpoint. Studies were also included if safety endpoints were examined.ResultsPalonosetron alone has been shown to improve CR and CC rates for patients receiving low, moderate, or high emetogenic chemotherapy. Rates were further improved with the addition of dexamethasone, a corticosteroid. Furthermore, the addition of neurokinin-1 receptor antagonists, such as netupitant markedly improved efficacy profiles compared to palonosetron alone. Aprepitant is an antiemetic that has exhibited positive results in combination with palonosetron. Recently, a new drug consisting of netupitant and palonosetron (NEPA) has demonstrated significantly more efficacious prevention of CINV. Regardless of the combination, palonosetron has been well tolerated. The most common adverse events were constipation, headache, fatigue, and dizziness, with the majority of patients describing them as only mild or moderate.ConclusionPalonosetron, alone or with other antiemetics, has improved CINV treatment due to its ability to significantly reduce delayed phases of CINV, compared to similar 5-HT3RAs. Palonosetron is both more effective than first generation 5-HT3RAs and safer, as it results in a smaller prolongation of the QTc interval, compared to other 5-HT3RAs.

Sustained antiemetic responses with APF530 (sustained-release granisetron) during multiple cycles of emetogenic chemotherapy.

A phase 3 trial in patients with cancer who received chemotherapy has shown that subcutaneous (SC) APF530, a sustained-delivery formulation of granisetron, is noninferior to palonosetron in preventing acute (0-24 hours) and delayed (>24-120 hours) chemotherapy-induced nausea and vomiting (CINV). To investigate the sustainability of APF530 antiemetic responses during multiple chemotherapy cycles. 1,395 patients receiving moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) were randomized either to APF530 250 or 500 mg SC (containing granisetron 5 or 10 mg, respectively) or palonosetron 0.25 mg intravenously before cycle 1 of chemotherapy. Patients who received palonosetron in cycle 1 were rerandomized in cycles 2-4 to APF530 250 or 500 mg; those who received APF530 in cycle 1 continued their APF530 dose. Between-group response rates were compared using the Fisher exact test. Complete response (CR; no emesis, no rescue medication) for APF530 500 mg with HEC increased from 81.3% to 87.8% over 4 cycles in the acute phase of CINV, and from 67.1% to 83.1% in the delayed phase. Rates were slightly lower with MEC. Within-cycle CR rates between APF530 doses showed no significant differences. With HEC, APF530 500 mg provided sustained CRs through 4 cycles of chemotherapy in 68.4% of patients in the acute phase and in 57.9% in the delayed phase; with MEC, corresponding CRs were 56.5% and 41.3%. Nausea prevention was nearly as effective as emesis prevention. Chemotherapy emetogenicity was classified according to Hesketh criteria during the time of this study. However, subsequent post hoc analyses indicate that reclassification according to newer ASCO emetogenicity guidelines did not alter the original study noninferiority conclusions. CR rates with APF530 during the acute and delayed phases of CINV in MEC and HEC were maintained over multiple cycles.

A meta-analysis of olanzapine for the prevention of chemotherapy-induced nausea and vomiting.

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life and is one of the reasons for the discontinuation of treatment. Olanzapine is known as an atypical antipsychotic agent, but it has been reported to be effective in treating refractory CINV due to its broad and potent inhibitory activity at multiple receptors involved in the nausea and vomiting pathways. This study was conducted to assess the efficacy of olanzapine for the prevention of CINV after moderately or highly emetogenic chemotherapy. After a search of Medline (Ovid), PubMed, CNKI, Wanfang and Weipu from 1990 to October 2013, all randomised controlled trials of olanzapine for the prevention of CINV were included in this study. The meta-analysis was performed using RevMan 5.0.19 software. 6 studies involving 726 total patients were included, of which 441 were Chinese oncology patients. We found that for both general populations and Chinese populations, antiemetic regimens including olanzapine are more effective at reducing CINV than regimens that do not include olanzapine, especially in the delayed phase of CINV.

Evaluation of Risk Factors Predicting Chemotherapy-Related Nausea and Vomiting: Results From a European Prospective Observational Study

ContextDemographic, personal, clinical, and behavioral factors predicting chemotherapy-induced nausea and vomiting (CINV) have been assessed in the past, but inconsistencies exist in the literature, studies have methodological shortcomings, and many risk factors have been examined in cross-sectional studies and univariate analyses. ObjectivesTo evaluate the predictive power of personal and treatment-related characteristics in the development of CINV, using a large and prospectively evaluated sample of a heterogeneous group of cancer patients receiving routine chemotherapy. MethodsThis was a multicountry, multisite prospective study over three cycles of chemotherapy. Adult patients from eight European countries about to receive highly and moderately emetogenic chemotherapy were recruited. Clinicians completed a case report form at or before the initial chemotherapy treatment, recording patient demographic and baseline clinical characteristics. Participants completed a daily patient diary for six days per chemotherapy cycle describing their CINV experience. Baseline patient data also included a history of nausea/vomiting (yes/no), patient expectation of nausea (0–100 mm visual analogue scale [VAS]), prechemotherapy anxiety (0–100 mm VAS), and prechemotherapy nausea (0–100 mm VAS) measured during the 24-hour period before chemotherapy initiation. ResultsThere were 991 evaluable patients with complete Cycle 1 data, 888 for Cycle 2 data, and 769 for Cycle 3 data. A complex picture of predictor variables was shown, with different contribution of variables to the acute, delayed, and overall phases of CINV. Key predictor variables included the use of antiemetics inconsistent with international guidelines, younger age, prechemotherapy nausea, and no CINV complete response in an earlier cycle (all at P < 0.05). Anxiety, history of nausea/vomiting, and expectations of nausea were important predictors for some phases and cycles but not consistently across the CINV pathway. ConclusionThe results of this study provide clarity for the relative contribution of a set of characteristics in the development of CINV. Following evidence-based clinical antiemetic guidelines is of paramount importance, alongside treating patients with increased risk for CINV more aggressively, which both could lead to more optimal CINV management. These data can assist clinicians in making decisions about the antiemetic management of their patients.

Sustainability of antiemetic responses with APF530 (sustained-release granisetron) during multiple cycles of moderately (MEC) and highly (HEC) emetogenic chemotherapy regimens: Results of a randomized phase III trial.

9626 Background: Patients receiving MEC or HEC were administered subcutaneous (SC) APF530 500 mg, a sustained delivery formulation of granisetron (10 mg). The complete antiemetic response rates (CR; no emetic episodes and no rescue medication) were non-inferior to those of palonosetron in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) (Grous et al. ASCO 2009, #9627). We report on sustainability of CR with APF530 (10 mg) during multiple chemotherapy cycles in this study. Methods: 1428 patients scheduled to receive single doses of MEC or HEC were randomized to APF530 SC (5 or 10 mg granisetron) or 0.25 mg palonosetron intravenously (IV) prior to cycle 1 (C1). In C2-4, patients who received palonosetron in C1 were randomized to APF530 5 or 10 mg; those who received APF530 continued with their C1 APF530 dose. Treatment cycles were separated by 7-28 days. CR rates were compared between cycles using McNemar’s test. Results: No significant differences in within-cycle CR occurred between APF530 doses during acute and delayed phases in C2-4 for MEC and HEC, but a trend toward higher CR rates was seen in successive cycles. For the 2 doses, CR was sustained across all 4 cycles in 56.5-62.6% and 68.4-71.7% in acute phase, and 41.8-42.4% and 57.5-57.9% in delayed phase with MEC and HEC, respectively. Examination of CR rates in C2, C3, or C4 compared with the rate in C1 showed that CR rates were sustained and that the proportion of patients with no CR in C1 but CR in later cycles was consistently higher than that of patients with CR in C1 but no CR later. For illustration, the table shows C4 CR and C1 CR for patients who received APF530 10 mg in C1 and C4. Conclusions: CR rates achieved with APF530 during acute and delayed phases of CINV in MEC and HEC were maintained over multiple cycles. Clinical trial information: NCT00343460. [Table: see text]

A Systematic Review and Meta-Analysis of Intravenous Palonosetron in the Prevention of Chemotherapy-Induced Nausea and Vomiting in Adults

We performed a systematic review and meta-analysis to compare treatment effectiveness and adverse effects in cancer patients receiving chemotherapy with palonosetron to prevent chemotherapy-induced nausea and vomiting (CINV). We identified randomized controlled clinical trials (RCT) comparing palonosetron with first-generation 5-HT3RA in the prevention of CINV in cancer patients. Meta-analyses were performed on homogeneous studies. Fixed or random-effects models were used to combine data. Eight eligible trials were identified, reporting outcomes on 3,592 patients. Meta-analyses showed statistically significant differences in favor of palonosetron compared with first-generation 5-HT3RA in prevention of acute CINV (p = .0003), delayed CINV (p < .00001), and overall phase of CINV (p < .00001). Subgroup analyses showed statistically significant differences in favor of both 0.25 mg and 0.75 mg of palonosetron in prevention of all phases of CINV. There were no statistically significant differences between 0.25 and 0.75 mg of palonosetron. Compared with the first-generation 5-HT3RA, 0.75 mg of palonosetron showed a statistically significant difference in the occurrence of constipation (p = .04). The use of palonosetron should be considered an integral part of adjuvant therapy for prevention of the acute, delayed, and overall phases of CINV. The 0.25 mg intravenous palonosetron dose is as effective as the 0.75 mg intravenous palonosetron dose. However, 0.75 mg intravenous palonosetron causes constipation more frequently than the first-generation 5-HT3RA.

Recommandations pour la prévention et le traitement des nausées et vomissements induits par la chimiothérapie

For the past two decades, significant developments have been made in supportive care for the management of chemotherapy-induced nausea and vomiting (CINV). A better understanding of the pathophysiology of vomiting and the introduction of two new classes of antiemetic agents with a high therapeutic index (serotonin type 3 receptor antagonists [anti-5HT3 or setrons] in the 1990s and neurokinin type 1 receptor antagonists [anti-NK1] in 2000), possibly combined with corticosteroids, have helped to improve the management of this distressing side effect, constantly feared by patients. It is essential to distinguish between the anticipatory, acute (first 24 hours) and delayed phases of CINV, to take into account the emetogenic potential of the different chemotherapy protocols (very low, low, moderate and high) together with individual risk factors. The authors would like to propose methodological and therapeutic recommendations for the primary and secondary prophylaxis of the acute and delayed phases of CINV, based on recent publications by international learned societies.

A daganatkezeléssel kapcsolatos hányinger és hányás csillapítása

Even today, nausea and vomiting are two of the most distressing adverse effects associated with tumor therapy. The authors give an overview of the mechanism and the trigger factors (emetogenic potential of the chemotherapies, the patient risk factors, and the used antiemetic drugs) of nausea and vomiting. A short summary will describe the antiemetic drugs focusing on metoclopramide, steroid and the currently widely used setron therapy which is effective only during the acute phase of chemotherapy-induced nausea and vomiting (CINV). In the treatment of CINV the latest improvement was the introduction of the neurokinin (NK1) receptor antagonist class. Currently the only available agent is aprepitant which is indicated to treat CINV in case of highly and moderately emetogenic chemotherapies. The pivotal phase III trials defined that aprepitant is the first drug that is able to protect against the delayed phase of CINV plus can improve the antiemetic therapy during the acute phase. Currently aprepitant is reimbursed in Hungary only after the failure of setron therapy in case of high dose (\>50 mg/m2) cisplatin protocols. The authors give a recommendation how to treat CINV based on the latest international antiemetic guidelines.The mechanism and the trigger factors of radiotherapy-induced nausea and vomiting (RINV) are different from CINV. For treatment of RINV metoclopramide (due to reimbursement regulation) and ondansetron can be used. In case of radio-chemotherapy the antiemetic treatment should follow the CINV guidelines.

Palonosetron Hydrochloride in the Treatment of Chemotherapy-Induced Nausea and Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is among the most unpleasant and stressful aspects of chemotherapy. Poorly controlled nausea and vomiting may have negative impacts on clinical treatment and quality of life. Clinical trials aimed at the prevention of CINV have focused on both acute and delayed phases of CINV. The use of first generation serotonin subtype 3 serotonin (5-HT3) receptor antagonists has significantly improved symptom control in acute CINV. However, they are less effective in controlling delayed CINV Palonosetron is a second generation 5-HT3 receptor antagonist with high potency, selectivity, prolonged half-life, and a unique allosteric binding mechanism. Previous trials which compared palonosetron to other first generation 5-HT3 antagonists had used the prevention of delayed CINV as a secondary end point. Recent data have demonstrated palonosetron, when used with a corticosteroid, was superior to granisetron in the prevention of delayed CINV as a primary end point. This article will review recently published literature focusing on mechanism of action, metabolism, pharmacokinetics, clinical efficacy, and safety of palonosetron in the treatment of CINV, specifically delayed CINV.

Aprepitant: A substance P antagonist for chemotherapy induced nausea and vomiting

The episodes of nausea and vomiting which follow each cycle of chemotherapy are the most troublesome side effect experienced by cancer patients. Introduction of ondansetron was a definite therapeutic advance in treating chemotherapy induced nausea and vomiting (CINV) with more effectiveness with corticosteroids. However, the protection remained largely limited to acute phase of CINV with little or no effect over delayed phase. Aprepitant, a drug that antagonizes the effect of substance P on neurokinin type 1 receptor showed promising results in controlling both phases of CINV. This drug is well absorbed orally with a t max of about four hours. The addition of aprepitant to ondansetron and dexamethasone was found to be superior to ondansetron and dexamethasone alone in clinical trials with patients taking high and moderate emetogenic chemotherapy. This drug also showed a good safety profile, but its inhibitory effect on CYP3A4 may result in clinically significant drug interactions needing dose modifications of co-administered drugs. The National Comprehensive Cancer Network guidelines for CINV recommends the use of aprepitant with high and moderately emetogenic anticancer drugs. Results of ongoing clinical trials with aprepitant and other agents of this new class of antiemetics are awaited and may alleviate the sufferings of cancer patients.

Chemotherapy-Induced Nausea and Vomiting

Chemotherapy-induced nausea and vomiting (CINV) impacts patient with cancer who are currently receiving chemotherapy. Risk factors identifying patients most likely to suffer from CINV are summarized. The pathophysiology of CINV is reviewed to provide rationale for recommending combination antiemetic therapy to optimally control CINV. The three phases of CINV, acute, delayed and anticipatory, are discussed including treatment recommendations for each phase. Studies assessing effective antiemetic regimen for control of acute CINV are summarized providing rationale for recommendations for the use of 5HT3-receptor antagonists in this population. Control of delayed CINV is controversial. Use of combinations of metoclopramide/dexamethasone is considered standard care. However, specific subsets of patients benefit from prolonged administration of 5HT3-receptor antagonists. Increased cost of 5HT3-receptor antagonists compared to traditional antiemetics is offset by increased efficacy and decreased adverse effects...