palonosetron and Neoplasms

Review the clinical evidence of tropisetron or palonosetron, an old- and new-generation serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor antagonist (RA), respectively, for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer, and evaluate any difference in efficacy trends. A literature search of the EMBASE and PubMed databases was performed to identify publications of intravenous (IV) tropisetron (generic forms or Navoban®) for the treatment of CINV in patients with various cancers. Data from the pivotal clinical studies evaluating the IV formulation of Aloxi® (palonosetron HCl) were also considered. The effectiveness and safety of each antiemetic was summarized. Sixteen papers for tropisetron fulfilled the inclusion criteria and were extracted for full analysis; publications from six pivotal palonosetron clinical trials were considered. No direct data comparisons could be made between the two drugs, due to the varying definitions of efficacy endpoints between studies. For tropisetron, the rates of no emesis were lower in patients receiving highly emetogenic chemotherapy (HEC) versus moderately emetogenic chemotherapy (MEC). For palonosetron, the rates of complete response (no emesis, no rescue medication) were comparable in the MEC and HEC settings, demonstrating the effectiveness of this agent in patients receiving HEC. Both antiemetics offered some protection against nausea, although lower rates of no nausea were achieved compared with rates of no emesis. Two trials that evaluated the efficacy of palonosetron and tropisetron within the same study reported that palonosetron was more effective than tropisetron in controlling delayed vomiting in the HEC and MEC settings, with significantly higher rates of no emesis observed (P≤0.01). Palonosetron was non-inferior or more efficacious in controlling CINV compared with other older 5-HT3RAs, such as dolasetron, ondansetron, and granisetron. Conversely, tropisetron was no more efficacious than ondansetron or granisetron. Both tropisetron and palonosetron were generally well tolerated, with adverse event profiles consistent with drugs of this class (e.g., headache, constipation, and diarrhea). These data suggest that palonosetron is a highly selective prophylactic agent that may have an improved therapeutic profile compared with tropisetron, and is a feasible treatment option for controlling CINV in patients with cancer.

Topics: Antineoplastic Agents; Female; Humans; Male; Nausea; Neoplasms; Palonosetron; Tropisetron; Vomiting

The aim is to conduct an updated systematic review comparing palonosetron to other 5-HT. Random-effects analysis model was used to generate odds ratio (OR), risk differences (RD) and accompanying 95% confidence intervals (CI). Funnel plots to assess for biases and cumulative meta-analyses to assess effect size over time were generated.. 4145 patients were randomized to palonosetron and 4911 received other 5-HT. Considering the vast amount of resources needed to conduct RCTs, resources should be dedicated to other prophylactic treatments/settings which have not been as well explored.

Topics: Antiemetics; Antineoplastic Agents; Humans; Nausea; Neoplasms; Odds Ratio; Palonosetron; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Radiation-induced nausea and vomiting (RINV) is a common side effect of radiotherapy and can affect up to 50-80% of patients, potentially causing detrimental effects to physical health, clinical efficacy, and patient quality of life. Antiemetic drugs act on receptors involved in the emesis pathway to block the uptake of neurotransmitters and inhibit stimulation of vomiting centers in the brain to prevent and treat RINV. The most commonly prescribed antiemetics for RINV are 5-hydroxytryptamine receptor antagonists (5-HT3 RA). Guidelines describing the optimal management of RINV are produced by the Multinational Association for Supportive Care in Cancer, the European Society of Medical Oncology, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. This review will present findings from research on antiemetic management for RINV conducted at our center.. A selective review of research conducted in a palliative outpatient radiotherapy clinic relating to antiemetic management for RINV was performed.. Several studies investigating the efficacy of different routes of administration, new antiemetic drug types, and novel combinations of antiemetics have been tested at our clinic to elucidate which approach provides the best response. These include studies on the use of ondansetron rapidly dissolving film, palonosetron, and the addition of a neurokinin-1 receptor antagonist to traditional 5-HT3 RA regimens.. These studies provide a framework for future research and could potentially inform changes to future guidelines to include the use of these novel regimens and techniques.

Topics: Adult; Ambulatory Care Facilities; Antiemetics; Humans; Medical Oncology; Middle Aged; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Ondansetron; Outpatients; Palonosetron; Quality of Life; Radiotherapy; Serotonin 5-HT3 Receptor Agonists; Serotonin Antagonists; Vomiting

Chemotherapy-induced nausea and vomiting (CINV), a common side effect of chemotherapy, can substantially impair a patient's quality of life, interfere with a patient's compliance with anticancer therapy, and result in the manifestation of adverse events such as electrolyte imbalance, dehydration and malnutrition. The most recent guidelines published by the Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO) recommend the combination of dexamethasone (DEX), a 5-hydroxytrypatmine-3 receptor antagonist (5-HT3RA), preferably palonosetron (PALO), and a neurokinin-1 receptor antagonist (NK1RA) for prophylactic treatment of CINV in patients receiving highly emetogenic chemotherapy (HEC). The aim of this review was to examine the efficacy of triple agent, as reported in randomized controlled trials (RCTs), compared to any other prophylactic treatments.. A literature search was conducted in Ovid MEDLINE(R), Embase Classic & Embase, and the Cochrane Central Register of Controlled Trials. The primary endpoint was the proportion of patients achieving complete response (CR) in the acute, delayed and overall phase. Secondary endpoints included the percentage of patients who achieved complete control (CC), no nausea and no vomiting in the acute, delayed and overall phases.. A total of 17 RCTs were included in this review, of which 3,146 patients were randomized to receive NK1RA, PALO and DEX, and 2,987 patients to receive other antiemetic treatments. The combination was not superior to other treatments in five endpoints-CC and CR in the acute phase, nausea and emesis control in the delayed phase, and nausea in the overall phase-but was superior in the other 11 endpoints. When looking only at HEC and moderately emetogenic chemotherapy (MEC) studies, the combination was only superior to others in three endpoints (delayed and overall CC, and overall emesis control) in HEC setting, which is less than the nine identified endpoints (delayed and overall CR, delayed and overall CC, acute and overall nausea control, and acute, delayed and overall phases for emesis control) in the MEC setting.. The combination of NK1RA, PALO and DEX is superior in the majority of assessed endpoints of this meta-analysis. Further studies should investigate the efficacy and safety of the triple regimen compared to regimens lacking NK1RA, to add to the discussions about whether future CINV prophylaxis guidelines should include NK1RA as a first-line treatment in the MEC setting.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Dexamethasone; Drug Combinations; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Palonosetron; Quinuclidines; Radiotherapy; Randomized Controlled Trials as Topic; Serotonin Antagonists; Vomiting

This update of the 2013 clinical practice guideline provides clinicians with guidance regarding the use of aprepitant and palonosetron for the prevention of acute chemotherapy-induced nausea and vomiting (CINV) in children. The recommendations were based on three systematic reviews. Substantive changes were made to the guideline recommendations including the inclusion of palonosetron to the 5-HT

Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Isoquinolines; Male; Nausea; Neoplasms; Palonosetron; Practice Guidelines as Topic; Quinuclidines; Serotonin Antagonists; Vomiting

A variety of triple antiemetic regimens are being used to prevent cisplatin-based chemotherapy induced delayed emesis and nausea in cancer patients. We performed a network meta-analysis to compare the efficacies of the different regimens. Electronic searches of the PubMed, Cochrane Library and MEDLINE databases were performed to identify randomized controlled trials, and data were analyzed using JAGS, Stata 14.0 and R project. The primary outcome was a complete response (CR). The secondary outcomes were no vomiting (NV) and no nausea (NN). Among the 398 studies identified, 10 were eligible and included, providing data on nine regimens. In the CR analysis, the absolute rank of netupitant + palonosetron + dexamethasone (NEPA) was 0.8579. In the NV and NN analyses, NEPA's absolute ranks were 0.8631 and 0.7902, respectively. The compliance of patients treated with rolapitant + granisetron + dexamethasone (RGD) was the best due to a low incidence of adverse events, and good compliance was also observed with NEPA. It was difficult to achieve good compliance with aprepitant + granisetron + dexamethasone (AGD). Overall, NEPA was the best regimen, and aprepitant + ondansetron + dexamethasone (AOD) is also worthy of recommendation because of its low cost and good effect. For patients with severe constipation, hiccups, asthenia and/or delayed nausea, RGD is worthy of consideration.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Granisetron; Humans; Isoquinolines; Morpholines; Nausea; Neoplasms; Network Meta-Analysis; Ondansetron; Palonosetron; Quinuclidines; Randomized Controlled Trials as Topic; Spiro Compounds; Treatment Outcome; Vomiting

Antiemetic prophylaxis for the prevention of chemotherapy-induced nausea and vomiting, and the development of new antiemetic drugs are expanding areas of research. However, studies of antiemetic prophylaxis in chemoradiotherapy have not been prioritised, and little is known about the proper timing, duration, and combination of antiemetic drugs for the prevention of chemoradiotherapy-induced nausea and vomiting (C-RINV).. The article summarises the available antiemetic studies, the evidence for antiemetic prophylaxis of C-RINV, and the future perspectives for antiemetic research in chemoradiotherapy.. Antiemetic prophylaxis for patients receiving concomitant chemoradiotherapy has, for many years, been an orphan research area. The distinction between acute and delayed nausea and vomiting does not apply to fractionated radiotherapy, and prophylaxis should be considered to cover the entire course of treatment and not only the acute and delayed chemotherapy-induced nausea and vomiting. The best prophylaxis in women receiving fractionated radiotherapy and concomitant weekly cisplatin is a combination of the neurokinin receptor antagonist fosaprepitant with palonosetron and dexamethasone. Even with this three-drug combination nausea is a significant problem and the effect of multi-receptor targeting antiemetics such as olanzapine and amisulpride should be explored in this setting.

Topics: Antiemetics; Antineoplastic Agents; Cisplatin; Drug Therapy, Combination; Humans; Isoquinolines; Morpholines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Receptors, Serotonin, 5-HT3; Vomiting

Current guidelines recommend the combination of a neurokinin-1 (NK1) receptor antagonist (RA) and a 5-hydroxytryptamine-3 (5-HT3) RA, together with corticosteroids, in order to prevent chemotherapy-induced nausea and vomiting with anthracycline-cyclophosphamide and highly emetogenic chemotherapy, and it is to be considered with moderately emetogenic chemotherapy. Netupitant and palonosetron (NEPA) is a fixed-dose combination of netupitant, a novel, highly selective NK1 RA, and palonosetron, a new-generation 5-HT3 RA, targeting two major emetic pathways in a single oral capsule. In clinical trials, NEPA administered on day 1 together with dexamethasone was highly effective and well tolerated in the prevention of chemotherapy-induced nausea and vomiting in patients with solid tumors undergoing moderately emetogenic chemotherapy or highly emetogenic chemotherapy. NEPA offers maximal convenience, and as a simple guideline-based regimen, has the potential to improve adherence to guidelines.

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Drug Combinations; Drug Interactions; Humans; Isoquinolines; Nausea; Neoplasms; Palonosetron; Pyridines; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Treatment Outcome; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists, appears to be the most effective agent in its class. Netupitant, is a new NK-1 receptor antagonist with a high binding affinity, a long half-life of 90 hours, is metabolized by CYP3A4, and is an inhibitor of CYP3A4. NEPA is an oral fixed-dose combination of netupitant and palonosetron which has recently been employed in Phase II and Phase III clinical trials for the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy (MEC and HEC). The clinical trials demonstrated that NEPA (300 mg of netupitant plus 0.50 mg of palonosetron) significantly improved the prevention of CINV compared to the use of palonosetron alone in patients receiving either HEC or MEC. The clinical efficacy was maintained over multiple cycles of chemotherapy. NEPA (Akynzeo(®)) has recently been approved by the Food and Drug Administration (FDA) to treat nausea and vomiting in patients undergoing cancer chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Isoquinolines; Molecular Structure; Nausea; Neoplasms; Palonosetron; Pyridines; Quinuclidines; Vomiting

5-Hydroxytryptamine3-receptor antagonists (5-HT3-RA) are the most widely used antiemetics in oncology, and although tolerability is high, QTC prolongation has been observed in some patients.. The purpose of this article is to outline the risk of cardiac adverse events (AEs) from 5-HT3-RAs, with focus on the three most commonly used, ondansetron, granisetron and palonosetron.. Most of the studies analyze electrocardiogram (ECG) changes after 5-HT3-RA administrations in healthy, young adults, or in noncancer patients to treat postoperative nausea and vomiting (PONV). Only a few studies have addressed ECG changes in cancer patients treated for chemotherapy-induced nausea and vomiting (CINV). Investigations in cancer patients are essential, because these patients are older and have a higher incidence of comorbidity, than those usually included in clinical trials. Furthermore, polypharmacy is frequent and drug-drug interactions between chemotherapy and other QTc-prolonging drugs may influence the pharmacokinetics and pharmacodynamics of the 5-HT3-RAs. During the next 10 - 15 years a huge increase in the number of cancer patients is expected, primarily in the group of 65-plus-year old. Therefore it will be crucial to address the incidence of cardiac AEs in cancer patients with known heart disease receiving chemotherapy and a 5-HT3 RA for the prophylaxis of CINV.

Topics: Aged; Antiemetics; Antineoplastic Agents; Cardiovascular Diseases; Granisetron; Humans; Isoquinolines; Long QT Syndrome; Nausea; Neoplasms; Ondansetron; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Nausea and vomiting are common adverse events in chemotherapy. In spite of the serious effects on the quality of life and further treatment, they remain overlooked by physicians, and no standard treatment has been developed. Neurokinin-1 (NK-1) receptor antagonists and palonosetron are the major agents in the standard regimen for treating moderately and highly emetogenic chemotherapy-induced nausea and vomiting (CINV). However, NK-1 receptor antagonists first became commercially available at the end of 2013 and palonosetron has not been extensively applied in China. Olanzapine was recommended as a therapy for moderate and severe CINV in antiemesis-clinical practice guidelines in oncology in 2014 for the first time. It is an atypical antipsychotic agent, which can block multiple receptors on neurotransmitters. During more than 10 years, olanzapine has demonstrated significant effects in preventing CINV and treating breakthrough and refractor CINV, which was observed in case reports, precise retrospective studies, and phase I, II and III clinical trials, with no grade 3 to 4 adverse events. In particular, it is superior to aprepitant and dexamethasone in delayed nausea and vomiting. Therefore, this compound is worthy of further investigation.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dexamethasone; Emetics; Humans; Isoquinolines; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Quinuclidines; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a concern for many cancer patients. It can have an enormous impact on quality of life. CINV occurring in the first 24 hours after treatment is considered acute, and CINV occurring on days 2 through 5 after treatment is considered delayed. Anticipatory nausea and depression can also occur when patients are reminded of their chemotherapy treatment. CINV can lead to weight changes, fatigue, and the need for additional medications. Even mild to moderate CINV can increase health care utilization and costs, as well as delay treatment. Nausea and vomiting are separate events, although their mechanisms are entwined. Drugs that stop vomiting do not necessarily treat nausea. Control of CINV allows patients to complete treatment and to minimize use of health care resources and additional medications. Current antiemesis agents, such as 5-hydroxytryptamine-3 (5-HT3) antagonists and neurokinin-1 (NK-1) antagonists, have markedly decreased hospitalization for chemotherapy and have nearly eliminated acute emesis. The second-generation 5-HT3 receptor palonosetron has a unique pharmacology that makes it especially effective at preventing delayed emesis.

Topics: Allosteric Regulation; Antiemetics; Antineoplastic Agents; Humans; Isoquinolines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Palonosetron; Pyridines; Quinuclidines; Receptors, Serotonin, 5-HT3; Serotonin; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) remains both a feared side effect of cancer treatment and a focus of many supportive care initiatives/guidelines. The class of medications known as serotonin receptor antagonists (5-HT3RAs) are integral in the prevention of CINV from both moderately and highly emetogenic chemotherapy. Palonosetron (ALOXI(®)), a second-generation 5-HT3RA, has a higher affinity for the 5-HT3 receptor, has a longer half-life and has unique interactions with the 5-HT3 receptor compared with the current first-generation 5-HT3RA such as ondansetron, granisetron, dolasetron and tropisetron. This may allow palonosetron an advantage in control of CINV. This review article examines the available evidence, the pharmacokinetics and the safety and tolerability of palonosetron in the prevention of CINV.

Topics: Antineoplastic Agents; Humans; Induction Chemotherapy; Isoquinolines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Vomiting

This review summarizes recent developments in the management of gastrointestinal symptoms experienced by cancer patients and provides a framework for education, assessment and monitoring, and treatment.. Although many viable treatment options exist, gastrointestinal symptoms - particularly nausea and vomiting, constipation, and diarrhea - continue to challenge both patients and clinicians. Current clinical guidelines now recommend that patients treated with moderate emetic risk chemotherapy regimens be preferentially treated with the 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, palonosetron, in combination with dexamethasone. A large randomized trial has also recently validated that single-dose fosaprepitant is equivalent to the standard 3-day, aprepitant regimen. New medications, such as skin patch delivery of granisetron for nausea or methylnaltrexone for constipation, show promise in both the management of symptoms and as preventive agents. The integration of complementary and alternative therapies, such as relaxation techniques, ginger, and electroacupuncture may also assist with symptom relief. Accurate assessment is essential, but often problematic, especially as the patient's experience of gastrointestinal distress is often disproportionate with objective measures. New methodologies that harness technology to collect patient-reported outcomes may improve the accuracy of assessment, provide a better picture of the patient's experience of gastrointestinal symptoms, and deliver a means to simultaneously monitor symptoms, educate patients, and collect longitudinal data.. Palliative management of gastrointestinal symptoms in advanced cancer patients requires a multipronged approach that entails effective assessment, judicious use of latest evidence-based approaches, and monitoring that incorporates both clinical measures and patient-reported outcomes. When combined with refinements in the overall clinical approach to symptom management, standardized instruments that streamline data collection and enable data warehousing will support better symptom management.

Topics: Antiemetics; Antineoplastic Agents; Dexamethasone; Gastrointestinal Diseases; Granisetron; Humans; Isoquinolines; Nausea; Neoplasms; Palliative Care; Palonosetron; Quinuclidines; Serotonin Antagonists; Treatment Outcome; Vomiting; Zingiber officinale

The objective of this work is to perform a systematic review and meta-analysis of all randomized controlled trials comparing a single intravenous dose of palonosetron (PAL) 0.25 mg with other 5-HT(3)R in patients receiving moderately or highly emetogenic (MoHE) chemotherapy.. Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were the incidence of acute and delayed nausea and vomiting. The side effects of each treatment were analyzed. A subgroup analysis was performed to evaluate the influence of the use of corticosteroids. The results are expressed as risk ratio (RR) and the correspondent 95% confidence interval (CI).. Five studies were included, with 2057 patients. PAL was compared with ondansetron, granisetron, and dolasetron. Patients in PAL group had less nausea, both acute (RR = 0.86; CI 95% = 0.76 to 0.96; p = 0.007) and delayed (RR = 0.82; CI95% = 0.75 to 0.89; p < 0.00001). They also had less acute vomiting (RR = 0.76; CI 95% = 0.66 to 0.88; p = 0.0002) and delayed vomiting (RR = 0.76; CI95% = 0.68 to 0.85; p < 0.00001). There were no statistical differences in side effects like headache (RR = 0.84; CI 95% = 0.61 to 1.17; p = 0.30), dizziness (RR = 0.40; CI 95% = 0.13 to 1.27; p = 0.12), constipation (RR = 1.29; CI 95% = 0.77 to 2.17; p = 0.33) or diarrhea (RR = 0.67; CI 95% = 0.24 to 1.85; p = 0.44). Patients receiving PAL presented less nausea and vomiting regardless of the use of corticoids. We found no statistical heterogeneity in the global analysis.. PAL was more effective than the other 5-HT(3)R in preventing acute and delayed CINV in patients receiving MoHE treatments, regardless of the use of concomitant corticosteroids.

Topics: Antiemetics; Antineoplastic Agents; Glucocorticoids; Humans; Isoquinolines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Vomiting

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.

Topics: Adult; Antiemetics; Antineoplastic Agents; Constipation; Dexamethasone; Headache; Humans; Infusions, Intravenous; Isoquinolines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles and patient characteristics (e.g., female gender, younger age, low alcohol consumption and history of motion sickness) are the major risk factors for CINV. This article provides a detailed description of palonosetron, a second-generation 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonist, which has been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. In recent studies, compared with the first-generation 5-HT(3) receptor antagonists, palonosetron in combination with dexamethasone demonstrated better control of delayed CINV in patients receiving highly emetogenic chemotherapy and had a similar safety profile. Owing to its efficacy in controlling both acute and delayed CINV, palonosetron may be very effective in the clinical setting of multiple-day chemotherapy and bone marrow transplantation.

Topics: Antiemetics; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Humans; Isoquinolines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Risk Factors; Safety; Serotonin Receptor Agonists; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) remains a significant detriment to patient quality of life and a major impediment to successful delivery of chemotherapy. CINV is generally categorized in three phases: acute (0-24 hours post treatment), delayed (24-120 hours post treatment), and anticipatory. Two agents represents an important step forward in the clinician's ability to control CINV. Palonosetron, a serotonin-receptor antagonist, and aprepitant, a neurokinin-1 receptor antagonist, have both shown efficacy in combating emesis in the acute and delayed phases; since these two agents are of different drug classes, there is the potential for augmented antiemetic efficacy when the two are used together, as shown in a recent phase III trial. Challenges remain in the prevention of CINV, such as improved detection, the development of clinically useful assessment tools, and the revision of treatment guidelines.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Humans; Isoquinolines; Medical Oncology; Morpholines; Nausea; Neoplasms; Palonosetron; Quality of Life; Quinuclidines; Vomiting

Important progress in the prophylaxis of chemotherapy-induced acute and delayed emesis has been achieved but some fundamental needs still remain that requires new, efficacious antiemetic drugs.. A critical review of the results of published studies of aprepitant, a new NK1 receptor antagonist, and of palonosetron, a 5-HT3 receptor antagonist with a longer half-life.. Aprepitant combined with dexamethasone and a 5-HT3 antagonist significantly increased the control of acute emesis with respect to dexamethasone and a 5-HT3 antagonist alone after cisplatin and moderately emetogenic chemotherapy. For cisplatin nausea, aprepitant combined with dexamethasone significantly increased the control of delayed emesis with respect to dexamethasone alone, while for moderately emetogenic chemotherapy aprepitant is superior to a 5-HT3 antagonist in the control of delayed emesis. Palonosetron showed superior or similar efficacy to ondansetron and dolasetron in patients submitted to moderately emetogenic chemotherapy and similar efficacy to ondansetron in patients submitted to cisplatin.. More studies are necessary comparing aprepitant alone or combined with dexamethasone with respect to the recommended antiemetic drugs for the prevention of delayed emesis induced by cisplatin and moderately emetogenic chemotherapy as well as for palonosetron combined with dexamethasone with respect to other 5-HT3 antagonists combined with dexamethasone.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Drug Therapy, Combination; Humans; Isoquinolines; Medical Oncology; Morpholines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Receptors, Serotonin, 5-HT3; Serotonin Antagonists; Vomiting

The need to control chemotherapy-induced emesis has stimulated research into anti-emetics. Emesis is not only unpleasant, but negatively impacts on global quality of life. The development of two new classes of drugs has been responsible for the major advances in anti-emesis. The 5 hydroxytryptamine3 (5HT3) antagonists in combination with dexamethasone significantly improved the control of acute post chemotherapy emesis, but delayed emesis which can last for several days was still problematic, yet its incidence was underestimated by clinicians. Both the control of acute and delayed emesis was improved when the neurokinin1 (NK1) receptor antagonists were added to 5HT3 antagonists and steroids. The complete control of delayed emesis was improved by 21% with little toxicity. The triple drug combination has become the standard of care for preventing the emesis associated with cytotoxic drugs of high emetic potential.

Topics: Administration, Oral; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Australia; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Granisetron; Humans; Indoles; Isoquinolines; Male; Neoplasms; Ondansetron; Palonosetron; Patient Satisfaction; Prognosis; Quality of Life; Quinolizines; Quinuclidines; Treatment Outcome; Tropisetron; Vomiting

Palonosetron is a potent and highly selective serotonin 5-HT(3) receptor antagonist that has been evaluated for the prevention of chemotherapy-induced nausea and vomiting. black triangle Intravenously administered palonosetron has a linear pharmacokinetic profile, with a long terminal elimination half-life ( approximate, equals 40 hours) and moderate (62%) plasma protein binding. In two randomised, double-blind trials in 1132 cancer patients receiving moderately emetogenic chemotherapy, intravenous palonosetron 0.25 mg was more effective than intravenous ondansetron 32 mg in producing a complete response (no emesis, no use of rescue medication) during acute (0-24 hours) or delayed (24-120 hours) phases, and similar to intravenous dolasetron 100 mg in acute, but more effective in delayed phase. Palonosetron 0.75 mg was similar to ondansetron (acute and delayed phase) or dolasetron (acute phase), but more effective than dolasetron in delayed phase. In patients receiving highly emetogenic chemotherapy (n = 667), the complete response rates during acute and delayed phases with intravenous palonosetron (0.25 or 0.75 mg) were similar to those seen in intravenous ondansetron 32 mg recipients in a randomised, double-blind trial. Intravenous palonosetron was generally well tolerated in clinical trials, with few adverse events being treatment related. Palonosetron had no significant effect on the corrected QT interval or laboratory parameters.

Topics: Antiemetics; Antineoplastic Agents; Humans; Injections, Intravenous; Isoquinolines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Randomized Controlled Trials as Topic; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Despite the advance in supportive care that occurred with the introduction of selective serotonin subtype 3 (5-HT3) receptor antagonists, control of chemotherapy-induced nausea and vomiting (CINV) with first-generation agents (ondansetron, dolasetron, and granisetron) is less than ideal. Palonosetron is a unique 5-HT3 receptor antagonist whose distinctive pharmacologic characteristics (ie, high 5-HT3 receptor binding affinity, prolonged half-life) result in superior clinical benefit. Superiority of palonosetron over ondansetron and dolasetron in the prevention of both acute and delayed CINV has been observed in each phase III trial conducted. Of note, such evidence of superiority has never been seen in US Food and Drug Administration (FDA) registration trials of other approved agents in this class. Recently approved by the FDA, palonosetron 0.25 mg intravenously is indicated for the prevention of acute nausea and vomiting associated with initial and repeat courses of moderately and highly emetogenic cancer chemotherapy. Unlike other 5-HT3 receptor antagonists, palonosetron is also indicated for prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. Palonosetron exhibits an excellent tolerability profile, with frequency, severity, and duration of adverse reactions similar to that of comparator agents. Unlike older agents that are considered therapeutically interchangeable at equipotent doses, palonosetron should be considered a clinically distinct and superior treatment for the prevention of CINV.

Topics: Acute Disease; Adult; Aged; Antiemetics; Antineoplastic Agents; Clinical Trials as Topic; Cytochrome P-450 CYP2D6; Dexamethasone; Female; Half-Life; Humans; Indoles; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Ondansetron; Palonosetron; Protein Binding; Quinolizines; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Vomiting

The triplet antiemetic regimen is administered to prevent chemotherapy-induced nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC). However, the superiority of palonosetron over first-generation 5-hydroxytryptamine-3 receptor antagonists in triplet antiemetic therapy remains unclear. In this study, we evaluated the efficacy of palonosetron (PALO) and granisetron (GRA) in triplet antiemetic therapy for CINV. This study included 267 patients who received MEC at our hospital between April 2017 and September 2020. Patients were pretreated with antiemetic therapy comprising PALO or GRA and dexamethasone on day 1 and aprepitant on days 1-3. We evaluated the rate of complete response (CR) (i.e., no vomiting and no use of rescue medication) in the acute phase (0-24 h), delayed phase (24-120 h), and overall phase (0-120 h) after first-cycle chemotherapy. Furthermore, multivariate analysis was conducted to identify risk factors for non-CR. The rate of CR in the overall and delayed phases was significantly higher in the PALO group (91.9 and 91.9%, respectively) than in the GRA group (74.1 and 75.5%, respectively). In the acute phase, the incidence was not different between the GRA and PALO groups (96.5 and 99.2%, respectively). Multivariate analysis revealed that female sex and the use of GRA were risk factors for non-CR. Subgroup analysis revealed the superiority of PALO over GRA in female patients, but not in male patients. In conclusion, PALO was more effective than GRA in triplet antiemetic therapy in preventing CINV during MEC, especially for female patients.

Topics: Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Drug Therapy, Combination; Female; Granisetron; Humans; Incidence; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Retrospective Studies; Treatment Outcome; Vomiting

No clinical trials have examined the effect of netupitant/palonosetron (NEPA) on chronic nausea in patients with cancer.. In this pilot randomized trial, we assessed the efficacy of NEPA and placebo on chronic nausea.. This double-blind, parallel, randomized trial enrolled patients with cancer and chronic nausea for at least 1 month, intensity ≥4/10 and not on moderately or highly emetogenic systemic therapies. Patients started with a placebo run-in period from days 1 to 5; those without a placebo response proceeded to the double-blinded phase between days 6 to 15 (NEPA: placebo 2:1 ratio). The primary outcome was within-group change in average nausea over the 24 hours on a 0-10 numeric rating scale between day 5 and 15.. Among the 53 enrolled patients, 46 proceeded to placebo run-in and 33 had blinded treatment (22 NEPA and 11 placebo). We observed a statistically significant within-group improvement in nausea numeric rating scale between day 5 and 15 in the NEPA group (mean change, -2.0; 95% CI, -3.1 to -0.8) and the placebo group (mean change, -2.3; 95% CI, -3.9 to -0.7). A complete response was achieved in 8 (38%) patients in the NEPA group and 2 (20%) in the placebo group by day 15. No grade 3-4 toxicities were attributed to NEPA. There were no statistically significant between-group differences for the primary/secondary outcomes.. NEPA and placebo were associated with similar magnitude of within-group improvement in chronic nausea without significant between-group differences (Clinicaltrials.gov NCT03040726).

Topics: Antiemetics; Antineoplastic Agents; Double-Blind Method; Drug Combinations; Humans; Isoquinolines; Nausea; Neoplasms; Palonosetron; Pilot Projects; Pyridines; Quinuclidines; Vomiting

Palonosetron has demonstrated non-inferiority to ondansetron for prevention of chemotherapy-induced nausea and vomiting in pediatric patients in the United States and Europe. We conducted a single-arm registration study to evaluate the efficacy, safety and pharmacokinetics of palonosetron in pediatric patients in Japan.. Key inclusion criteria were age of 28 days to 18 years and malignant disease for which initial highly emetogenic chemotherapy or moderately emetogenic chemotherapy was planned. Patients received palonosetron at 20 μg/kg over at least 30 s intravenously before the start of highly emetogenic chemotherapy or moderately emetogenic chemotherapy and received dexamethasone on Days 1-3. The primary endpoint was the proportion of patients achieving a complete response in the overall phase (0-120 h) in Course 1, and its threshold was set at 30%.. From December 2016 to June 2019, 60 patients were enrolled, and 58 received at least one dose of palonosetron. The proportion of patients achieving a complete response during the overall phase was 58.6% (95% confidence interval, 44.9%-71.4%), showing the primary endpoint was met (P < 0.0001). Treatment-related adverse events occurred in two patients (3.4%). Regarding the pharmacokinetics of palonosetron, neither the plasma concentration immediately after administration nor the area under the plasma concentration-time curve from time 0 to infinity differed significantly among the age groups.. We demonstrated the efficacy of palonosetron in pediatric patients receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy and confirmed the appropriateness of the 20 μg/kg dose, regardless of age, considering the safety and pharmacokinetic profiles.. JapicCTI-163305, registered 6 June 2016.

Topics: Antiemetics; Antineoplastic Agents; Child; Dexamethasone; Double-Blind Method; Humans; Infant, Newborn; Isoquinolines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Vomiting

The purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)-induced nausea and vomiting.. Patients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by sex, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6.. A total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], -7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, -2.3%; 95% CI, -13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, -7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups.. In all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Benzimidazoles; Dexamethasone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Prognosis; Prospective Studies; Quality of Life; Surveys and Questionnaires; Vomiting; Young Adult

The 5-hydroxytryptamine-3 receptor antagonist palonosetron (PALO) is approved (United States/Europe) as an oral formulation for prevention of chemotherapy-induced nausea and vomiting in adult cancer patients undergoing moderately emetogenic chemotherapy (MEC) for the acute phase only, in the United States, or as intravenous (IV) formulation in patients undergoing MEC or highly emetogenic chemotherapy. This phase III study compares the efficacy/safety of oral versus IV PALO in Chinese patients.. Chemotherapy-naive patients with solid tumours scheduled for MEC received oral PALO 0.50 mg or IV PALO 0.25 mg. The primary objective was to demonstrate non-inferiority in terms of patients with complete response in the acute phase (0-24 hr post-chemotherapy).. Complete response rates (acute phase), evaluated in 318/320 randomised patients, were 84.6% and 85.9% for oral and IV PALO respectively. Non-inferiority was demonstrated; the two formulations showed similar efficacy/safety.. Non-inferiority of oral versus IV PALO in the acute phase was demonstrated in Chinese patients.. CTR20140711.

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Breast Neoplasms; Carcinoma; China; Colorectal Neoplasms; Dexamethasone; Double-Blind Method; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Stomach Neoplasms; Vomiting; Young Adult

Palonosetron (PG) is a newer, safe, and effective long-acting 5-HT3 antagonist commonly used in adults, but data in children are limited. A randomized controlled trial was carried out among children with cancer during their first cycle of moderate or highly emetogenic chemotherapy to receive either PG or ondansetron (OG) with the aim of comparing their efficacy, safety, and cost-effectiveness. In total, 200 children (mean age, 8 y, male:female=1.8:1) were recruited, 100 in each arm. Complete response, defined as no vomiting, in acute (<24 h), delayed (24 to 120 h), and overall phases (0 to 120 h) was observed in 88%, 88%, and 81% of cases, respectively, for PG versus 84%, 79%, and 72%, respectively, for OG (P=0.42, 0.09 and 0.21, respectively). Complete protection rates, defined as no nausea and vomiting in children above 6 years of age, in acute, delayed, and overall phases were 84%, 81%, and 73%, respectively, for PG versus 79%, 67%, and 60%, respectively, for OG (P=0.44, 0.06 and 0.10, respectively). Overall, the efficacy and safety of PG in the prevention of chemotherapy-induced nausea and vomiting was comparable with OG, but PG was a more cost-effective and suitable choice for busy centers in resource-limited countries.

Topics: Adolescent; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Male; Nausea; Neoplasms; Ondansetron; Palonosetron; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) in children remains to be a major side effect despite antiemetic treatment. Palonosetron is a new generation 5-HT. A prospective, randomized, double-blind, parallel controlled study was conducted in 0-18 years old cancer patients administered highly emetogenic chemotherapy, with different dosage of palonosetron or ondansetron, both followed by dexamethasone. The patients were observed for vomiting and nausea from 0 to 120 hr after chemotherapy initiation. All adverse events (AEs) during the study period were recorded. This study was registered with the Chinese Clinical Trial Registry, number ChiCTR-TRC-14004891.. Between August 2014 and July 2016, 565 patients were randomly assigned to receive 5 μg/kg palonosetron (n = 185), 10 μg/kg palonosetron (n = 186), and 3 × 150 μg/kg ondansetron (n = 194), of whom 181, 185, and 189, respectively, were included in the efficacy analysis. Complete response (CR) rates during the acute phase were 69.1, 69.7, and 64.6%, respectively, in the 5 μg/kg palonosetron, 10 μg/kg palonosetron, and ondansetron groups. In the delayed phase, 10 μg/kg palonosetron (CR, 53.5%) showed superiority to 5 μg/kg palonosetron (CR, 39.8%) and ondansetron (CR, 32.8%) groups (P < 0.05). The most frequently observed drug-related AEs were nervous system disorders, mainly headache, with an incidence of 2.8, 2.2, and 2.6% in each group, respectively.. Combination of palonosetron plus dexamethasone is highly effective in controlling acute and delayed CINV, with palonosetron superior to ondansetron.

Topics: Adolescent; Antiemetics; Child; Child, Preschool; Dexamethasone; Double-Blind Method; Female; Humans; Infant; Infant, Newborn; Isoquinolines; Male; Nausea; Neoplasms; Ondansetron; Palonosetron; Prospective Studies; Quinuclidines; Vomiting

The aim of this phase II study was to evaluate the efficacy and safety of two doses (10 and 5 mg) of olanzapine in combination with standard antiemetic treatment (aprepitant, palonosetron, and dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC).. A multi-institutional, double-blind, randomized phase II, dose-finding study of olanzapine was performed in patients with a malignant solid tumor who were receiving HEC with cisplatin (≥ 50 mg/m. 153 patients were randomized to the 10 mg group (n = 76) or the 5 mg group (n = 77). The CR rate in the delayed phase was 77.6% (80% CI: 70.3-83.8, P = 0.01) in the 10 mg group and 85.7% (80% CI: 79.2-90.7, P < 0.001) in the 5 mg group (P value for H. Both doses of 10 and 5 mg olanzapine provided a significant improvement in delayed emesis. A dose of 5 mg olanzapine was determined as the recommended dose for a further phase III study based on higher CR and lower somnolence rates.. UMIN000014214.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Cisplatin; Dexamethasone; Double-Blind Method; Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Neoplasms; Olanzapine; Palonosetron; Quinuclidines; Treatment Outcome; Vomiting

Chemotherapy-induced vomiting is a common adverse effect of cancer treatment. We assessed the non-inferiority of palonosetron versus ondansetron in prevention of acute chemotherapy-induced vomiting in children with cancer in 2-18 years of age.. In this single-center, open-label, randomized study, children receiving moderate and high emetogenic chemotherapy were assigned to get either ondansetron or palonosetron in addition to other antiemetic prophylaxis. The primary efficacy endpoint was the proportion of children with complete response during the acute phase of the first on-study chemotherapy cycle. Non-inferiority was assessed by demonstration of lower limit of the 97.5% confidence interval for differences in complete response rates in palonosetron arm to be superior by - 15%. Risk factors for suboptimal response and the cost of administration of two drugs were also analyzed.. A total of 108 children were analyzed and various factors likely to influence response were equally distributed in two arms. These 108 patients received 412 blocks of chemotherapy. During the acute phase, complete responses were recorded in 72.2% (39/54) and 83.3% (45/54) receiving ondansetron and palonosetron, respectively (ΔCR + 11.1%). The lower limit of 97.5% confidence interval (- 6.95-28.39) for this difference was greater than - 15% in palonosetron arm. Only statistically significant risk factor that predisposed response was use of dexamethasone (p value < 0.01). The cost associated with ondansetron administration was significantly higher compared to palonosetron.. Palonosetron is non-inferior and cost-effective compared to ondansetron for prevention of acute chemotherapy-induced vomiting (CIV) in children receiving moderate and high emetogenic chemotherapy.

Topics: Adolescent; Antiemetics; Child; Child, Preschool; Double-Blind Method; Female; Humans; Male; Nausea; Neoplasms; Ondansetron; Palonosetron; Vomiting

NEPA, an oral fixed combination of the NK1RA netupitant (300 mg) and clinically/pharmacologically distinct 5-HT3RA palonosetron (PALO, 0.50 mg), is the first fixed antiemetic combination to have been approved. A single oral NEPA capsule plus dexamethasone (DEX) given before anthracycline-cyclophosphamide (AC) and non-AC highly emetogenic chemotherapy (HEC) showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) over PALO plus DEX for 5 days postchemotherapy. The safety of NEPA was well-established in the phase II/III clinical program in 1169 NEPA-treated patients. An intravenous (i.v.) formulation of the NEPA combination (fosnetupitant 235 mg plus PALO 0.25 mg) has been developed.. This randomized, multinational, double-blind, stratified (by sex and country) phase III study (NCT02517021) in chemotherapy-naïve patients with solid tumors assessed the safety of a single dose of i.v. NEPA infused over 30 min before initial and repeated cycles of HEC. Patients received either i.v. NEPA or oral NEPA, both with oral DEX on days 1-4. Safety was assessed primarily by treatment-emergent adverse events (AEs) and electrocardiograms.. A total of 404 patients completed 1312 cycles. The incidence and type of treatment-emergent AEs were similar for both treatment groups with the majority of AEs as mild/moderate in intensity. There was no increased incidence of AEs in subsequent cycles in either group. The incidence of treatment-related AEs was similar and relatively low in both groups (12.8% i.v. NEPA and 11.4% oral NEPA during the entire study), with constipation being the most common (6.4% i.v. NEPA, 6.0% oral NEPA). No serious treatment-related AEs occurred in either group. No infusion site or anaphylactic reactions related to i.v. NEPA occurred. No clinically relevant changes in QTc and no cardiac safety concerns were observed.. Intravenous NEPA was well-tolerated with a similar safety profile to oral NEPA in patients with various solid tumors receiving HEC.

Topics: Administration, Intravenous; Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Induction Chemotherapy; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Prognosis; Pyridines; Survival Rate; Vomiting

To investigate across multiple cycles the efficacy and safety of palonosetron in the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients receiving highly or moderately emetogenic chemotherapy (HEC/MEC).. Patients were randomly assigned to 10, 20 μg/kg palonosetron or 3 × 150 μg/kg ondansetron for up to four cycles of HEC/MEC.. In all on-study chemotherapy cycles, complete response rates were higher in patients in the 20 μg/kg palonosetron group than the ondansetron group. Treatment-emergent adverse events were comparable between the palonosetron 20 μg/kg and ondansetron groups.. Over four cycles of HEC/MEC, 20 μg/kg palonosetron was an efficacious and safe treatment for the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients.

Topics: Adolescent; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Isoquinolines; Nausea; Neoplasms; Ondansetron; Palonosetron; Quinuclidines; Treatment Outcome; Vomiting

Purpose We examined the efficacy and safety of thalidomide (THD) for the prevention of delayed nausea and vomiting in patients who received highly emetogenic chemotherapy (HEC). Patients and Methods In a randomized, double-blind, active-controlled, phase III trial, chemotherapy-naive patients with cancer who were scheduled to receive HEC that contained cisplatin or cyclophosphamide-doxorubicin/epirubincin ≥ 50 mg/m

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Dexamethasone; Double-Blind Method; Doxorubicin; Epirubicin; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Thalidomide; Vomiting; Young Adult

This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25-120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0-120 h) CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles.. Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1-4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles.. NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.

Topics: Adult; Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dexamethasone; Double-Blind Method; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Pyridines; Quinuclidines; Vomiting; Young Adult

Palonosetron has shown efficacy in the prevention of chemotherapy-induced nausea and vomiting in adults undergoing moderately or highly emetogenic chemotherapy. We assessed the efficacy and safety of palonosetron versus ondansetron in the prevention of chemotherapy-induced nausea and vomiting in paediatric patients.. In this multicentre, multinational, double-blind, double-dummy, phase 3 study, paediatric patients aged between 0 and younger than 17 years, who were naive or non-naive to chemotherapy, and scheduled to undergo moderately or highly emetogenic chemotherapy for the treatment of malignant disease were randomised centrally (1:1:1) to receive up to four cycles of 10 μg/kg or 20 μg/kg palonosetron on day 1, or three 150 μg/kg doses of ondansetron on day 1, scheduled 4 h apart, according to a static central permuted block randomisation scheme by an interactive web response system. Randomisation was stratified according to age and emetogenicity. Treatment allocation was masked to project team members involved in data collection and analysis, and members of the investigator's team. The primary endpoint was complete response (no vomiting, retching, or use of rescue drugs) during the acute phase (0-24 h post-chemotherapy) of the first on-study chemotherapy cycle, as assessed in the population of randomly assigned patients who received moderately or highly emetogenic chemotherapy and an active study drug. The primary efficacy objective was to show the non-inferiority of palonosetron versus ondansetron during the acute phase (0-24 h post-chemotherapy) of the first on-study chemotherapy cycle through comparison of the difference in the proportions of patients who achieved a complete response with palonosetron (πT) minus ondansetron (πR) versus a preset non-inferiority margin (δ -15%). To be considered as non-inferior to ondansetron, for at least one of the doses of palonosetron, the lower limit of the 97·5% CI for the weighted sum of the differences in complete response rates had to be superior to -15%. Safety was assessed, according to treatment received. This study is registered with ClinicalTrials.gov, number NCT01442376, and has been completed.. Between Sept 12, 2011, and Oct 26, 2012, we randomly assigned 502 patients; 169 were assigned to receive 10 μg/kg palonosetron, 169 to receive 20 μg/kg palonosetron, and 164 to receive 3 × 150 μg/kg ondansetron, of whom 166, 165, and 162, respectively, were included in the efficacy analysis. In the acute phase, complete responses were recorded in 90 (54%) patients in the 10 μg/kg palonosetron group, 98 (59%) in the 20 μg/kg palonosetron group, and 95 (59%) in the ondansetron group. Non-inferiority versus ondansetron was shown for 20 μg/kg palonosetron in the acute phase (weighted sum of the differences in complete response rates 0·36% [97·5% CI -11·7 to 12·4]; p=0·0022). Non-inferiority versus ondansetron was not shown for 10 μg/kg palonosetron in the acute phase (weighted sum of the differences in complete response rates -4·41% [97·5% CI -16·4 to 7·6]). In the first on-study treatment cycle, treatment-emergent adverse events were reported in 134 (80%) of 167 patients who received 10 μg/kg palonosetron, 113 (69%) of 163 who received 20 μg/kg palonosetron, and 134 (82%) of 164 who received ondansetron. The most common drug-related treatment-emergent adverse events were nervous system disorders, mainly headache, which occurred in three (2%) patients who received 10 μg/kg palonosetron, one (<1%) patient who received 20 μg/kg palonosetron, and two (1%) patients who received ondansetron. The incidence of serious adverse events in the first on-study treatment cycle was lower in the 20 μg/kg palonosetron group (43 [26%]) than in the 10 μg/kg palonosetron group (52 [31%]) and the ondansetron group (55 [34%]).. Non-inferiority was shown for 20 μg/kg palonosetron during the acute phase of the first on-study chemotherapy cycle. 20 μg/kg palonosetron is now indicated by the European Medicines Agency and the US Food and Drug Administration for the prevention of chemotherapy-induced nausea and vomiting in paediatric patients aged 1 month to younger than 17 years.. Helsinn Healthcare.

Topics: Adolescent; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Humans; Infant; Internationality; Isoquinolines; Male; Nausea; Neoplasms; Ondansetron; Palonosetron; Quinuclidines; Treatment Outcome; Vomiting

There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC).. Patients with a malignant solid tumor who would receive HEC containing 50 mg/m(2) or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2-4) and aprepitant (125 mg on day 1 and 80 mg on days 2-3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0-120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea).. Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0-120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0-24 h) period, while at the delayed (24-120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0-120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369).. The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point.. UMIN000004863.

Topics: Adult; Aged; Antineoplastic Agents; Cisplatin; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Granisetron; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin Antagonists; Vomiting

Subcutaneous APF530 provides controlled sustained release of granisetron to prevent acute (0-24 h) and delayed (24-120 h) chemotherapy-induced nausea and vomiting (CINV). This randomized, double-blind phase 3 trial compared APF530 and palonosetron in preventing acute and delayed CINV after moderately (MEC) or highly emetogenic chemotherapy (HEC).. Patients receiving single-day MEC or HEC received single-dose APF530 250 or 500 mg subcutaneously (SC) (granisetron 5 or 10 mg) or intravenous palonosetron 0.25 mg. Primary objectives were to establish APF530 noninferiority to palonosetron for preventing acute CINV following MEC or HEC and delayed CINV following MEC and to determine APF530 superiority to palonosetron for preventing delayed CINV following HEC. The primary efficacy end point was complete response (CR [using CI difference for APF530-palonosetron]). A lower confidence bound greater than -15 % indicated noninferiority.. In the modified intent-to-treat population (MEC = 634; HEC = 707), both APF530 doses were noninferior to palonosetron in preventing acute CINV after MEC (CRs 74.8 % [-9.8, 9.3] and 76.9 % [-7.5, 11.4], respectively, vs. 75.0 % palonosetron) and after HEC (CRs 77.7 % [-11.5, 5.5] and 81.3 % [-7.7, 8.7], respectively, vs. 80.7 % palonosetron). APF530 500 mg was noninferior to palonosetron in preventing delayed CINV after MEC (CR 58.5 % [-9.5, 12.1] vs. 57.2 % palonosetron) but not superior in preventing delayed CINV after HEC. Adverse events were generally mild and unrelated to treatment, the most common (excluding injection-site reactions) being constipation.. A single subcutaneous APF530 injection offers a convenient alternative to palonosetron for preventing acute and delayed CINV after MEC or HEC.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Delayed-Action Preparations; Double-Blind Method; Female; Granisetron; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Prospective Studies; Quinuclidines; Severity of Illness Index; Treatment Outcome; Vomiting

This study aims to compare the efficacy and safety of oral palonosetron with intravenous (IV) palonosetron for the prevention of cisplatin-related chemotherapy-induced nausea and vomiting (CINV).. A multinational, randomized, double-blind study enrolling adult chemotherapy-naive patients with malignant solid tumors scheduled to receive cisplatin-based highly emetogenic chemotherapy (HEC). Patients received oral palonosetron (0.50 mg) or IV palonosetron (0.25 mg), each with oral dexamethasone. The primary objective was to demonstrate non-inferiority in terms of patients with a complete response (CR, no emesis/no rescue medication) within the acute phase (0-24 h after chemotherapy administration).. Of the 743 patients randomized, 739 received study medications and 738 were included in the full analysis set. The CR rate in the acute phase was high for both groups (oral 89.4 %; IV 86.2 %). As this difference in proportions (stratum-adjusted Cochran-Mantel-Haenszel method) was 3.21 % (99 % confidence interval (CI) -2.74 to 9.17 %), non-inferiority was demonstrated (since the lower limit of the 99 % CI was closer to zero than the predefined margin of 15 %). Treatment-emergent adverse events (TEAEs) related to the study drug were rare (oral 3.2 %; IV 6.5 %). No TEAEs related to study drug leading to discontinuation were reported.. Non-inferiority of oral versus IV palonosetron was demonstrated. The CR rate in the acute phase was >86 % in both patient groups. The safety profiles were comparable.

Topics: Administration, Intravenous; Administration, Oral; Antiemetics; Cisplatin; Dexamethasone; Double-Blind Method; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Vomiting

The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1-3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2-3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at -15% (study treatment group - control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1-3 (difference, 2.5%; 95% confidence interval [CI]: -7.8%-12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2-3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Dexamethasone; Female; Humans; Irinotecan; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Organoplatinum Compounds; Oxaliplatin; Palonosetron; Quality of Life; Quinuclidines; Serotonin Antagonists; Treatment Outcome

APF530 is a novel sustained-release formulation of granisetron. In a Phase III trial, APF530 500 mg was noninferior to palonosetron 0.25 mg in preventing acute chemotherapy-induced nausea and vomiting (CINV) after moderately (MEC) or highly emetogenic chemotherapy (HEC) and delayed CINV after MEC, but not superior in preventing delayed CINV after HEC. Emetogenicity was classified by Hesketh criteria; this reanalysis uses newer American Society of Clinical Oncology criteria.. Complete responses (no emesis or rescue medication) after cycle one were reanalyzed after reclassification of MEC and HEC by American Society of Clinical Oncology criteria.. APF530 maintained noninferiority to palonosetron.. Single-dose APF530 is a promising alternative to palonosetron for preventing acute and delayed CINV after MEC or HEC. The Clinicaltrials.gov identifier for this study is NCT00343460.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Delayed-Action Preparations; Female; Granisetron; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin Antagonists; Treatment Outcome; Vomiting

Preventing chemotherapy-induced nausea and vomiting (CINV) is integral to treatment success in patients with cancer. This analysis was undertaken to assess the relative efficacy and safety of palonosetron versus older 5HT3 RAs in preventing CINV associated with moderately or highly emetogenic chemotherapy.. Patient-level data from four randomized, double-blind, phase III trials comparing palonosetron 0.25 or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg were analyzed. Endpoints included complete response (CR: no emesis and no rescue antiemetics) in the acute (0-24 h), delayed (>24-120 h), and overall (0-120 h) postchemotherapy periods (primary), complete control (CC: no emesis, no rescue antiemetics, and no more than mild nausea), number of emetic episodes, and nausea severity.. CR rates were significantly higher for palonosetron (n = 1,787) versus older 5HT3 RAs (n = 1,175) in the delayed (57 vs 45 %, P < 0.0001) and overall periods (51 vs 40 %, P < 0.0001); odds ratios (95 % CI) in the acute, delayed, and overall periods were 1.15 (0.98-1.34), 1.62 (1.40-1.88), and 1.56 (1.34-1.81), respectively. Significant differences in CC rates and nausea severity were observed for the delayed and overall periods and in emetic episodes for all three periods. The incidence of treatment-related adverse events was similar with palonosetron (0.25 mg, 20.0 %; 0.75 mg, 26.5 %) and older 5HT3 RAs (27.5 %).. Palonosetron is more effective than older 5HT3 RAs for controlling CINV in the delayed and overall postchemotherapy periods.

Topics: Antiemetics; Antineoplastic Agents; Double-Blind Method; Female; Granisetron; Humans; Indoles; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Ondansetron; Palonosetron; Quinolizines; Quinuclidines; Serotonin Antagonists; Treatment Outcome; Vomiting

Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV) or oral routes, but subcutaneous (SC) administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron.. Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC0-24h, t1/2, and Cmax observed with each route of administration by analysis of variance (ANOVA).. From October 2009 to July 2010, 25 evaluable patients were included. AUC0-24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p=0.160). Bioavalability of SC palonosetron was 118% (95% IC: 69-168). Cmax was lower with SC than with IV route and was reached 15 minutes following SC administration.. Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy.. ClinicalTrials.gov NCT01046240.

Topics: Administration, Intravenous; Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Injections, Subcutaneous; Isoquinolines; Male; Middle Aged; Neoplasms; Palonosetron; Platinum; Quinuclidines; Treatment Outcome; Vomiting

Safe, effective and convenient antiemetic regimens that preserve benefit over repeated cycles are needed for optimal supportive care during cancer treatment. NEPA, an oral fixed-dose combination of netupitant, a highly selective NK1 receptor antagonist (RA), and palonosetron (PALO), a distinct 5-HT3 RA, was shown to be superior to PALO in preventing chemotherapy-induced nausea and vomiting after a single cycle of highly (HEC) or moderately (MEC) emetogenic chemotherapy in recent trials. This study was designed primarily to assess the safety but also to evaluate the efficacy of NEPA over multiple cycles of HEC and MEC.. This multinational, double-blind, randomized phase III study (NCT01376297) in 413 chemotherapy-naïve patients evaluated a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) given on day 1 with oral dexamethasone (DEX). An oral 3-day aprepitant (APR) regimen + PALO + DEX was included as a control (3:1 NEPA:APR randomization). In HEC, DEX was administered on days 1-4 and in MEC on day 1. Safety was assessed primarily by adverse events (AEs), including cardiac AEs; efficacy by complete response (CR: no emesis, no rescue).. Patients completed 1961 total chemotherapy cycles (76% MEC, 24% HEC) with 75% completing ≥4 cycles. The incidence/type of AEs was comparable for both groups. Most frequent NEPA-related AEs included constipation (3.6%) and headache (1.0%); there was no indication of increasing AEs over multiple cycles. The majority of AEs were mild/moderate and there were no cardiac safety concerns based on AEs and electrocardiograms. The overall (0-120 h) CR rates in cycle 1 were 81% and 76% for NEPA and APR + PALO, respectively, and antiemetic efficacy was maintained over repeated cycles.. NEPA, a convenient single oral dose antiemetic targeting dual pathways, was safe, well tolerated and highly effective over multiple cycles of HEC/MEC.

Topics: Antineoplastic Agents; Double-Blind Method; Drug Combinations; Humans; Isoquinolines; Nausea; Neoplasms; Palonosetron; Pyridines; Quinuclidines; Vomiting

Prevention of chemotherapy-induced nausea and vomiting (CINV) is crucial for maintaining the quality of life of cancer patients. Female patients have been underrepresented in previous clinical studies of aprepitant or palonosetron. We performed a prospective multicenter study to investigate the efficacy and safety of triple therapy comprising these two agents and dexamethasone in female cancer patients receiving chemotherapy that included cisplatin (≥ 50 mg/m(2)).. Aprepitant was administered at a dose of 125 mg before chemotherapy on day 1 and at 80 mg on days 2 and 3. Palonosetron (0.75 mg) was given before chemotherapy on day 1. Dexamethasone was administered at a dose of 9.9 mg before chemotherapy on day 1 and at 6.6 mg on days 2-4. The primary endpoint was the the proportion of patients with a complete response (CR no vomiting and no use of rescue medication) throughout the overall period (0-120 h post-chemotherapy).. Ninety-six women (median age 55 years) were enrolled. The overall CR rate was 54.2 %. CR was obtained during the acute phase (0-24 h post-chemotherapy) and the delayed phase (24-120 h post-chemotherapy) in 87.5 and 56.3 % of the patients, respectively. The most common adverse reactions were constipation and fatigue (reported by three patients each).. Exhibition of a favorable overall CR rate over existing two-drug combinations suggests that the triple therapy regimen used in the present study is effective and tolerable in patients with gynecological malignancies receiving cisplatin-based chemotherapy. Female patients may have a higher risk of developing CINV.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Neoplasms; Palonosetron; Prospective Studies; Quality of Life; Quinuclidines; Vomiting

To investigate the electronic anti-nausea instrument (EANI) combined with hydrochloride palonosetron for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy.. Patients who received highly emetogenic chemotherapy were randomly assigned to a treatment group (60 patients) treated with EANI combined with hydrochloride palonosetron, and control group (also 60 patients) given only hydrochloride palonosetron. Chemotherapy related nausea and vomiting were observed and recorded in both groups of patients from the start till the end of chemotherapy.. Complete control rates of vomiting in treatment and control group were 40%, and 35%, respectively, without any statistical ly significant difference (p> 0.05); however the response rates are 95.0%, 78.3%, respectively, with statistical difference (p< 0.05). Complete control rates of nausea in treatment and control group were 36.7%, 30%, respectively, without statistical difference (p> 0.05); but the response rates are 90.0%, 76.7%, respectively, with statistical difference (p<0.05).. EANI combined with hydrochloride palonosetron for prevention of nausea and vomiting induced by chemotherapy could be more effective than hydrochloride palonosetron alone, and can be recommended for use in prevention and treatment of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Carmustine; Cisplatin; Cyclophosphamide; Dacarbazine; Doxorubicin; Electric Stimulation Therapy; Epirubicin; Humans; Ifosfamide; Isoquinolines; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Vomiting; Young Adult

Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated.. Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion).. Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome.. Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Dexamethasone; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Vomiting

Data from two randomized trials were pooled to further characterize the effectiveness of palonosetron combined with dexamethasone in the setting of highly emetogenic chemotherapy.. The analysis included 1411 patients who were randomized to receive palonosetron or ondansetron/granisetron intravenously on day 1 plus either 1-day or 3-day dexamethasone dosing. The primary end point was complete response (no vomiting and no rescue antiemetics over days 1-5) in cycle one. Data across the studies were analyzed by the Mantel-Haenszel method.. The vast majority of patients received either cisplatin (62%) or anthracycline plus cyclophosphamide (34%). The palonosetron regimen provided a 12 percentage-point improvement in the rate of overall complete response compared with the control regimen (49.2 vs 37.3%; odds ratio: 1.65; 95% CI: 1.33-2.04; p < 0.0001). The frequency of no delayed nausea at all daily periods was consistently higher in the palonosetron group.. The current analysis confirmed that palonosetron plus dexamethasone improved control of highly emetogenic chemotherapy-induced nausea and vomiting throughout 5 days postchemotherapy to a significantly greater extent than the combination including older 5-HT3 antagonists.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Treatment Outcome; Vomiting

Chemotherapy-induced nausea and vomiting remain among the most feared adverse effects for cancer patients.. The aim of this study was to evaluate the efficacy and safety of a combination of aprepitant, palonosetron and dexamethasone as antiemetic prophylaxis in patients receiving multiple-day cisplatin-based chemotherapy.. Forty-one solid cancer patients received aprepitant, palonosetron and dexamethasone during a 3-day cisplatin-based chemotherapy. Primary end-point was complete response in the overall phase (day 1 until 5 days after the end of chemotherapy).. Aprepitant in combination with palonosetron and dexamethasone was safe, with hiccups (31.7%), fatigue (17.1%), headache (14.6%) and constipation (12.2%) the most common treatment-related adverse events, mostly mild. Complete response was seen in 58.5% of patients in the overall phase. In 23 patients receiving aprepitant in combination with palonosetron and dexamethasone more than one cycle (range: 2-5 cycles), the cumulative emetic protection rate after five cycles was 0.82.. This study shows aprepitant in combination with palonosetron and dexamethasone is safe and effectively controls chemotherapy-induced nausea and vomiting in patients undergoing 3-day cisplatin-based chemotherapy, moreover, the efficacy is maintained during multiple cycles.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Constipation; Dexamethasone; Drug Administration Schedule; Drug Therapy, Combination; Fatigue; Female; Headache; Hiccup; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Palonosetron; Prospective Studies; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Vomiting; Young Adult

Olanzapine has been shown to be a safe and effective agent for the prevention of chemotherapy-induced nausea and vomiting (CINV). Olanzapine may also be an effective rescue medication for patients who develop breakthrough CINV despite having received guideline-directed CINV prophylaxis.. A double-blind, randomized phase III trial was performed for the treatment of breakthrough CINV in chemotherapy-naive patients receiving highly emetogenic chemotherapy (cisplatin, ≥ 70 mg/m2 or doxorubicin, ≥ 50 mg/m2 and cyclophosphamide, ≥ 600 mg/m2), comparing olanzapine to metoclopramide. Patients who developed breakthrough emesis or nausea despite prophylactic dexamethasone (12 mg IV), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) pre-chemotherapy and dexamethasone (8 mg p.o. daily, days 2-4) post-chemotherapy were randomized to receive olanzapine, 10 mg orally daily for 3 days or metoclopramide, 10 mg orally TID for 3 days. Patients were monitored for emesis and nausea for 72 h after taking olanzapine or metoclopramide. Two hundred seventy-six patients (median age 62 years, range 38-79; 43% women; Eastern Cooperative Oncology Group (ECOG) PS 0,1) consented to the protocol. One hundred twelve patients developed breakthrough CINV and 108 were evaluable.. During the 72-h observation period, 39 out of 56 (70%) patients receiving olanzapine had no emesis compared to 16 out of 52 (31%) patients with no emesis for patients receiving metoclopramide (p < 0.01). Patients without nausea (0, scale 0-10, M.D. Anderson Symptom Inventory) during the 72-h observation period were those who took olanzapine, 68% (38 of 56), and metoclopramide, 23% (12 of 52) (p < 0.01). There were no grade 3 or 4 toxicities.. Olanzapine was significantly better than metoclopramide in the control of breakthrough emesis and nausea in patients receiving highly emetogenic chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Cisplatin; Cyclophosphamide; Dexamethasone; Double-Blind Method; Doxorubicin; Female; Humans; Isoquinolines; Male; Metoclopramide; Middle Aged; Morpholines; Nausea; Neoplasms; Olanzapine; Palonosetron; Quinuclidines; Vomiting

Palonosetron (Aloxi(®), Onicit(®)) is a pharmacologically unique 5-HT3 receptor antagonist (RA) approved as a single IV injection for the prevention of nausea and vomiting induced by chemotherapy (CINV) of either moderate or highly emetogenic potential (MEC and HEC, respectively). An oral palonosetron formulation has been developed and compared to the IV formulation.. In this multinational, multicenter, double-blind, double-dummy, dose-ranging trial, 651 patients were randomly assigned to receive one of the following as a single dose prior to moderately emetogenic chemotherapy: oral palonosetron 0.25, 0.50, and 0.75 mg or IV palonosetron 0.25 mg. Patients were also randomized (1:1) to receive dexamethasone 8 mg IV or matched placebo on day 1. The primary endpoint was complete response (CR; no emesis, no rescue therapy) during the acute phase (0-24 h).. Acute CR rates were 73.5, 76.3, 74.1, and 70.4 % for all patients receiving the palonosetron 0.25, 0.50, and 0.75 mg oral doses, and for IV palonosetron 0.25 mg, respectively; delayed CR (24-120 h) rates were 59.4, 62.5, 60.1, and 65.4 %, and overall CR (0-120 h) rates were 53.5, 58.8, 53.2, and 59.3 %, respectively. The addition of dexamethasone improved emetic control (acute CR rate) by at least 15 % for all groups except oral palonosetron 0.25 mg, where the acute CR improvement was approximately 7 %. Adverse events were similar in nature, incidence, and intensity for all oral and IV palonosetron groups, and were the expected adverse events for 5-HT3 RAs (primarily headache and constipation).. Oral palonosetron has a similar efficacy and safety profile as IV palonosetron 0.25 mg and may be the preferred formulation in certain clinical situations. Among the tested oral treatments, a palonosetron 0.50-mg oral dose has been favored for the prevention of CINV in patients receiving moderately emetogenic chemotherapy due to a numerical gain in efficacy without a side effect disadvantage.

Topics: Administration, Oral; Adult; Aged; Antiemetics; Antineoplastic Agents; Dexamethasone; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin Antagonists; Treatment Outcome; Vomiting

Nausea and vomiting are among the major problems occurring during and after the chemotherapy treatments of cancer patients. The recently developed 5-HT(3) antagonists have proved much more effective than former agents. Several studies have shown that these agents cause certain ECG changes. We aimed to evaluate the ECG changes caused by palonosetron, one of the new 5-HT(3) antagonists.. Our study includes a total of 50 patients diagnosed with solid-organ tumors receiving chemotherapy. The patients were applied 12-lead ECG before palonosetron infusion. Afterwards, subsequent ECGs were applied on the 30th, 60th, and 90th minutes following the infusion of palonosetron. Arterial blood pressure was measured before and after the infusion. PR, QRS, QT, QTmax, QTmin, QTd, Pmax, Pmin, Pd, QTc, QTcmax, QTcmin, and QTcd values were evaluated for each ECG.. We did not detect significant correlations between the systolic and diastolic blood pressures before and after (30 min) palonosetron infusion (p > 0.05). However, there was a statistically significant decrease in heart rate (p = 0.000). The evaluation of ECG findings revealed that there was a significant prolongation in PR distance, as shown by the comparisons of 0 min with 30, 60, and 90 min. On the other hand, there was no significant difference in QRS, QT, QTmax, QTmin, QTd, Pmax, Pmin, Pd, QTc, QTcmax, QTcmin, and QTcd values (p > 0.05).. In this study, we revealed that palonosetron did not cause any severe rhythmic disorders or symptomatic ECG changes. We concluded that it could be safe to administer palonosetron antiemetically.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Blood Pressure; Electrocardiography; Female; Heart Rate; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Time Factors; Vomiting; Young Adult

Prevention of chemotherapy-induced nausea and vomiting (CINV) is of great importance for the completion of multiple cycles of cancer chemotherapy. Palonosetron is a second-generation 5-HT(3) receptor antagonist with proven efficacy for both acute and delayed CINV. This study was designed to assess the safety and efficacy of 0.75 mg palonosetron in repeated cycles of highly emetogenic chemotherapy or anthracycline-cyclophosphamide combination (AC/EC).. We gave 0.75 mg palonosetron to 538 patients 30 min prior to ≥ 50 mg/m(2) cisplatin or AC/EC on day 1. Prophylactic dexamethasone was administered on days 1-3. The primary endpoint was the incidence rate of adverse events (AEs). The secondary endpoint was complete response rate (CR, defined as no emesis and no rescue medication) throughout the study period.. Treatment-related AEs were seen in 44% (237 of 538 patients). Serious AEs were seen in 4% (23 of 538 patients), all considered unrelated or unlikely to be related to palonosetron. Only one patient discontinued the study due to a treatment-related AE. No trend toward worsening of AEs was observed in subsequent cycles of chemotherapy. Complete response rates were maintained throughout repeated cycles.. The extraordinary safety profile and maintenance of efficacy of 0.75 mg palonosetron combined with dexamethasone were demonstrated throughout repeated chemotherapy cycles.

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Drug Therapy, Combination; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Vomiting

The goal of pharmacological prophylaxis of chemotherapy-induced nausea and vomiting (CINV) should be the elimination of both nausea and vomiting symptoms during all planned chemotherapy cycles. The aim of this study was to assess the efficacy of a single dose of palonosetron and dexamethasone to prevent CINV and to guarantee an adequate food intake (FI) in patients receiving several cycles of multiple day-based chemotherapy (MD-CT).. Patients with advanced cancer but without a compromised nutritional status (bone mass index ≥ 18.5) were treated with 0.25 mg palonosetron plus 20 mg dexamethasone before MD-CT. The MD-CT regimen was either epirubicin plus ifosfamide or paclitaxel plus cisplatin and ifosfamide. Nausea, vomiting, and FI were monitored in a 7-day diary. Complete response (CR: no vomiting and no rescue therapy) was the primary endpoint, while complete control (CC: CR and no more than mild nausea) and the evaluation of FI were secondary endpoints. The endpoints were evaluated during the overall timescale (0-168 h) of the chemotherapy regimen.. Fifty patients were enrolled, 80% of whom achieved CR and 78% achieved CC. During the six chemotherapy cycles, CR and CC ranged from 76% to 88% and from 62% to 88%, respectively. Moreover, patients with CR had a significantly (p < 0.0001) higher weekly food intake compared with patients not achieving CR.. This trial was the first to assess the efficacy of palonosetron and dexamethasone for the prevention of both nausea and vomiting in patients receiving multiple cycles of MD-CT. In this trial, the ability of patients to intake an adequate amount of food each week was correlated with nausea, thus providing clinicians with an objective parameter for the measurement of the effects of nausea. A single dose of palonosetron and dexamethasone was able to prevent CINV in most patients receiving 3 days of chemotherapy during all planned chemotherapy cycles.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Dexamethasone; Drug Therapy, Combination; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Prospective Studies; Quinuclidines; Serotonin Antagonists; Treatment Outcome; Vomiting

The objective of this study was to compare the efficacy and tolerability of palonosetron and granisetron in a Chinese population receiving highly emetogenic cisplatin-based chemotherapy or moderately emetogenic chemotherapy. Patients were stratified by chemotherapy with cisplatin (yes/no) and then randomly assigned to receive either palonosetron (0.25 mg i.v.) in the first cycle followed by granisetron (3 mg i.v.) in the second cycle or vice versa. The primary efficacy endpoint was the proportion of patients with complete response 0-24 h post-chemotherapy administration. The proportions of patients with complete response 24-120 and 0-120 h following chemotherapy were also compared. Of the 144 patients randomized, 36 (25%) received 60-80 mg/m(2) cisplatin; 66 of 72 patients in the palonosetron to granisetron group and 56 of 72 patients in the granisetron to palonosetron group completed treatment with both antiemetics. The efficacy and safety analyses included 128 palonosetron treatments and 138 granisetron treatments. Palonosetron consistently produced numerically higher complete response rates than granisetron in the acute phase (0-24 h, 71.09 vs. 65.22%), the delayed phase (24-120 h, 60.16 vs. 55.80%), and overall (0-120 h, 53.13 vs. 50.00%) though the differences were not significant. Both palonosetron and granisetron were well tolerated. Palonosetron was well tolerated and effective in preventing acute and delayed chemotherapy-induced nausea and vomiting in a Chinese population. When used as monotherapy, 0.25-mg palonosetron was not inferior to 3-mg granisetron for preventing vomiting following highly or moderately emetogenic chemotherapy.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Asian People; China; Cross-Over Studies; Double-Blind Method; Female; Granisetron; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin Antagonists; Survival Rate; Treatment Outcome; Vomiting; Young Adult

The incidence of overall (acute and delayed) chemotherapy-induced nausea and vomiting (CINV) events among patients treated with single- and multi-day low emetogenic chemotherapy (LEC) is not well established. We studied a cohort of patients receiving LEC and antiemetic prophylaxis with palonosetron (Group 1) versus other 5-HT(3) receptor antagonists (5-HT(3)-RAs) (Group 2), to determine the overall rate of CINV and the proportion of patients experiencing delayed CINV (days 2-7 of a CT cycle) in a hospital outpatient setting.. Patients aged ≥18 years with cancer diagnosis initiating single-day and multi-day LEC for the first time between 4/1/2007 and 3/31/2009 were identified from the Premier Perspective database. CINV events (ICD-9-CM codes for nausea, vomiting, or volume depletion or CINV-related rescue medications) were assessed descriptively. A generalized linear multivariate regression model was developed, estimating the overall CINV event rate among Group 1 and 2 patients in the follow-up period (first of eight chemotherapy [CT] cycles or 6 months).. In the follow-up period, out of a total of 10,137 overall CINV events (single-day and multi-day LEC), 8783 events (86.6%) were identified in single-day LEC treated patients. Within single-day LEC treated events, in the first cycle, of 3184 events, 2996 (94.1%) events were delayed. Average number of delayed events per patient remained consistent throughout the eight cycles (3.1 [1st cycle] vs. 2.9 [8th cycle]; P = 0.842]). Among 2439 patients on antiemetic prophylaxis with a 5-HT(3)-RA, 10.1% (n = 247) initiated palonosetron. Regression analysis indicated that Group 1 patients (versus Group 2) had a 15.2% reduction in CINV event rate per CT cycle; P = 0.0403. Study limitations include potential lack of generalizability, absence of data on certain confounders including alcohol consumption and prior history of motion sickness, potential underestimation of incidence of uncontrolled CINV, and inability to draw conclusions pertaining to cause and effect relationship.. In this retrospective analysis, delayed CINV comprised a major proportion of overall CINV among cancer diagnosed patients on single-day LEC. Additionally, palonosetron prophylaxis was associated with a significantly lower overall CINV event rate versus other 5-HT(3)-RA prophylaxis in single- and multi-day LEC treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Databases, Factual; Female; Follow-Up Studies; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin Antagonists; Time Factors; Vomiting

Aim of the present phase II non-randomized study was to verify whether palonosetron might be able to prevent acute and especially delayed CINV for either HEC or MEC, starting from the second chemotherapy cycle, in patients who had failed to respond to a different antiemetic 5-HT(3) antagonist during the first cycle. Stratification factor was age <65 years vs. > or =65 years of patients included. Forty-seven cancer patients (23 elderly and 24 non-elderly) scheduled to receive HEC or MEC regimens who had experienced CINV grade 3-4 during the first chemotherapy course and for whom the same course of chemotherapy regimen was further scheduled were enrolled. Complete response (CR) and complete control (CC) rates for the acute, delayed and overall phases of CINV were not significantly different between elderly and non-elderly patients. Palonosetron was safe: only grade 1-2 toxicities were observed with a peak of 12.9% for asthenia with no significant difference between elderly and non-elderly patients. In conclusion, single dose palonosetron (250 microg) should be considered a safe and effective second generation 5-HT(3) antagonist in the prevention of nausea and vomiting induced by HEC or MEC, irrespective of patients' age.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Dexamethasone; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin Antagonists; Vomiting

This clinical trial was conducted to evaluate the efficacy and safety of Palonosetron in preventing chemotherapy-induced vomiting (CIV) among the Chinese cancer patients.. Two hundred and forty patients were scheduled to be enrolled and randomized to receive a single intravenous dose of palonosetron 0.25 mg, or granisetron 3 mg, 30 min before receiving highly emetogenic chemotherapy. The primary efficacy endpoint was the complete response (CR) rate for acute CIV (during the 0-24-h interval after chemotherapy). Secondary endpoints included the CR rates for delayed CIV (more than 24 h after chemotherapy).. Two hundred and eight patients were accrued and received study medication. CR rates for acute CIV were 82.69% for palonosetron and 72.12% for granisetron, which demonstrated that palonosetron was not inferior to granisetron in preventing acute CIV. Comparisons of CR rates for delayed CIV yielded no statistical difference between palonosetron and granisetron groups and did not reveal non-inferiority of palonosetron to granisetron. Adverse events were mostly mild to moderate, with quite low rates among the two groups.. A single dose (0.25 mg) of palonosetron is not inferior to a single dose (3 mg) of granisetron in preventing CIV and possesses an acceptable safety profile in the Chinese population.

Topics: Adult; Antiemetics; Antineoplastic Agents; Asian People; China; Double-Blind Method; Female; Granisetron; Humans; Isoquinolines; Male; Middle Aged; Neoplasms; Palonosetron; Quinuclidines; Serotonin Antagonists; Vomiting

Palonosetron is a second-generation 5-hydroxytryptamine 3 (5-HT(3))-receptor antagonist that has shown better efficacy than ondansetron and dolasetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy, and similar efficacy to ondansetron in preventing CINV in patients receiving highly emetogenic chemotherapy. In this phase III, multicentre, randomised, double-blind, double-dummy, stratified, parallel-group, active-comparator trial, we assessed the efficacy and safety of palonosetron versus granisetron for chemotherapy-induced nausea and vomiting, both of which were administered with dexamethasone in patients receiving highly emetogenic chemotherapy.. Between July 5, 2006, and May 31, 2007, 1143 patients with cancer who were receiving highly emetogenic chemotherapy (ie, cisplatin, or an anthracycline and cyclophosphamide combination [AC/EC]) were recruited from 75 institutions in Japan, and randomly assigned to either single-dose palonosetron (0.75 mg), or granisetron (40 microg/kg) 30 min before chemotherapy on day 1, both with dexamethasone (16 mg intravenously) on day 1 followed by additional doses (8 mg intravenously for patients receiving cisplatin or 4 mg orally for patients receiving AC/EC) on days 2 and 3. A non-deterministic minimisation method with a stochastic-biased coin was applied to the randomisation of patients. Covariates known to effect emetic risk, such as sex, age, and type of highly emetogenic chemotherapy, were used as stratification factors of minimisation to ensure balance between the treatment groups. Primary endpoints were the proportion of patients with a complete response (defined as no emetic episodes and no rescue medication) during the acute phase (0-24 h postchemotherapy; non-inferiority comparison with granisetron) and the proportion of patients with a complete response during the delayed phase (24-120 h postchemotherapy; superiority comparison with granisetron). The non-inferiority margin was predefined in the study protocol as a 10% difference between groups in the proportion of patients with complete response. The palonosetron dose of 0.75 mg was chosen on the basis of two dose-determining trials in Japanese patients. All patients who received study treatment and highly emetogenic chemotherapy were included in the efficacy analyses (modified intention to treat). This trial is registered with ClinicalTrials.gov, number NCT00359567.. 1114 patients were included in the efficacy analyses: 555 patients in the palonosetron group and 559 patients in the granisetron group. 418 of 555 patients (75.3%) in the palonosetron group had complete response during the acute phase compared with 410 of 559 patients (73.3%) in the granisetron group (mean difference 2.9% [95% CI -2.70 to 7.27]). During the delayed phase, 315 of 555 patients (56.8%) had complete response in the palonosetron group compared with 249 of 559 patients (44.5%) in the granisetron group (p<0.0001). The main treatment-related adverse events were constipation (97 of 557 patients [17.4%] in the palonosetron group vs 88 of 562 [15.7%] in the granisetron group) and raised concentrations of serum aminotransferases (aspartate aminotransferase: 24 of 557 [4.3%] vs 34 of 562 [6.0%]; alanine aminotransferase: 16 of 557 [2.9%] vs 33 of 562 [5.9%]); no grade 4 main treatment-related adverse events were reported.. When administered with dexamethasone before highly emetogenic chemotherapy, palonosetron exerts efficacy against chemotherapy-induced nausea and vomiting which is non-inferior to that of granisetron in the acute phase and better than that of granisetron in the delayed phase, with a comparable safety profile for the two treatments.. Taiho Pharmaceutical (Tokyo, Japan).

Topics: Adult; Antiemetics; Antineoplastic Agents; Dexamethasone; Double-Blind Method; Female; Granisetron; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin Antagonists; Vomiting

The aim of our study was to evaluate the efficacy of a single-dose palonosetron plus dexamethasone to control emesis in patients (pts) receiving HEC. Moreover, we evaluated the amount of their food intake (FI) in the week following therapy, in order to measure any reduction of calories consumption related to Chemotherapy-induced nausea and vomiting (CINV).. Patients affected with advanced cancer were treated with palonosetron 250 mcg plus dexamethasone 20 mg before HEC. Nausea, vomiting, and FI were monitored by a 7-day diary. Complete Response (CR: no vomiting and no rescue therapy) was the primary endpoint, Complete Control (CC: CR and no more than mild nausea) and the evaluation of FI were the secondary endpoints. The endpoints were evaluated during the acute (0-24 h), the delayed (25-168 h) and overall (0-168 h) phases.. Thirty-five patients were enrolled; 85.7% and 82.9% of patients achieved CR and CC respectively, during the acute phase; 82.9% and 77.1% of patients achieved CR and CC, during the delayed phase; 80% and 77.1% of patients achieved CR and CC, during the overall phase. During the acute phase, patients with a CC without nausea had a median daily FI of 1,575 kcal, whereas patients with CC and presence of mild nausea had a median daily FI of 1,040 kcal (-535 kcal; p < 0.0001).. Our preliminary results confirm the efficacy of a single-dose palonosetron plus dexamethasone to prevent both acute and delayed nausea and vomiting. Moreover, the efficacy of palonosetron in nausea and vomiting control seems to warrant adequate caloric intake in these patients.

Topics: Aged; Antiemetics; Antineoplastic Agents; Dexamethasone; Drug Therapy, Combination; Eating; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Prospective Studies; Quinuclidines; Serotonin Antagonists; Vomiting

The purpose of this study is to determine the control of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) and highly emetogenic chemotherapy (HEC) with the combined use of palonosetron and olanzapine, and dexamethasone with the dexamethasone given on day 1 only.. Forty chemotherapy-naive patients received on the day of chemotherapy, day 1, an anti-emetic regimen consisting of dexamethasone, palonosetron, and olanzapine. Patients continued olanzapine for days 2-4 after chemotherapy administration. Patients recorded daily episodes of emesis, daily symptoms utilizing the M.D. Anderson Symptom Inventory, and the utilization of rescue therapy.. For the first cycle of chemotherapy, the complete response (no emesis, no rescue) for the acute period (24 h post-chemotherapy) was 100%, the delayed period (days 2-5 post-chemotherapy) 75%, and the overall period (0 120 h post-chemotherapy) 75% in 8 patients receiving HEC and was 97, 75, and 72% in 32 patients receiving MEC. Patients with no nausea for the acute period was 100%, the delayed period 50%, and the overall period 50% in 8 patients receiving HEC and was 100, 78, and 78% in 32 patients receiving MEC.. The complete response and control of nausea in subsequent cycles of chemotherapy were not significantly different from cycle one.. Olanzapine combined with a single dose of dexamethasone and a single dose of palonosetron was very effective in controlling acute and delayed CINV in patients receiving both HEC and MEC.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Benzodiazepines; Dexamethasone; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Outcome Assessment, Health Care; Palonosetron; Quinuclidines; United States; Vomiting

The objective of this multicenter, phase II, open-label study was to evaluate the safety and efficacy of the newest 5-hydroxytryptamine3 (5-HT3) receptor antagonist, palonosetron, plus dexamethasone and aprepitant in preventing nausea and vomiting in patients receiving moderately emetogenic chemotherapy. Eligible patients received a single intravenous dose of palonosetron (0.25 mg on day 1 of chemotherapy), along with 3 daily oral doses of aprepitant (125 mg on day 1,80 mg on days 2 and 3) and dexamethasone (12 mg on day 1,8 mg on days 2 and 3). Efficacy and safety data were obtained from patient diaries and adverse event reporting. Fifty-eight patients were evaluable; 47% were women with breast cancer and 52% received cyclophosphamide-based chemotherapy. The proportion of patients with complete response (no emesis and no rescue medication) was 88% during the acute (0-24 hours) interval, 78% during the delayed (> 24-120 hours) interval, and 78% during the overall (0-120 hours post chemotherapy) interval. More than 90% of patients during all time intervals had no emetic episodes, and between 57% and 71% of patients reported no nausea during each of the 5 days post chemotherapy. Treatment was well tolerated, with no unexpected adverse events. These data demonstrate that palonosetron in combination with dexamethasone and aprepitant is safe and highly effective in preventing chemotherapy-induced nausea and vomiting in the days following administration of moderately emetogenic chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Dexamethasone; Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin Antagonists; Vomiting

Although currently available 5-hydroxytryptamine type 3 receptor (5-HT3) antagonists are effective, not all patients receiving these agents achieve adequate control of chemotherapy-induced nausea and vomiting (CINV). Palonosetron, a potent and highly selective 5-HT3 antagonist with a strong affinity for 5-HT3 and a prolonged plasma elimination half-life, may provide a longer duration of action than other approved agents.. One hundred and sixty-one patients were randomly assigned to receive a single intravenous bolus dose of palonosetron (0.3, 1, 3, 10, 30 or 90 microg/kg) before administration of highly emetogenic chemotherapy, with no pretreatment with corticosteroids.. The four highest doses of palonosetron were similarly effective during the first 24 h, producing clearly higher complete response (CR) (no emesis, no rescue medication) rates in the 3, 10, 30 and 90 microg/kg groups (46%, 40%, 50% and 46%, respectively) than in the 0.3-1 microg/kg group (24%) of evaluable patients (n = 148). The 3 microg/kg dose was identified as the lowest effective dose. A single dose of palonosetron showed prolonged efficacy in preventing delayed emesis, with approximately one-third of patients who received palonosetron 10 or 30 microg/kg maintaining a CR throughout the 7-day period following chemotherapy administration. Dose-proportional increases in pharmacokinetic parameters and a long plasma half-life (43.7-128 h) were observed. Palonosetron was well-tolerated, with no dose-response effect evident for the incidence or intensity of adverse events.. Palonosetron is an effective and well-tolerated agent for the prevention of CINV following highly emetogenic chemotherapy, with 3 and 10 microg/kg identified as the lowest effective palonosetron doses.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Intravenous; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Vomiting

Palonosetron is a potent and highly selective serotonin 5-HT(3) receptor antagonist that has been evaluated for the prevention of chemotherapy-induced nausea and vomiting. black triangle Intravenously administered palonosetron has a linear pharmacokinetic profile, with a long terminal elimination half-life ( approximate, equals 40 hours) and moderate (62%) plasma protein binding. In two randomised, double-blind trials in 1132 cancer patients receiving moderately emetogenic chemotherapy, intravenous palonosetron 0.25 mg was more effective than intravenous ondansetron 32 mg in producing a complete response (no emesis, no use of rescue medication) during acute (0-24 hours) or delayed (24-120 hours) phases, and similar to intravenous dolasetron 100 mg in acute, but more effective in delayed phase. Palonosetron 0.75 mg was similar to ondansetron (acute and delayed phase) or dolasetron (acute phase), but more effective than dolasetron in delayed phase. In patients receiving highly emetogenic chemotherapy (n = 667), the complete response rates during acute and delayed phases with intravenous palonosetron (0.25 or 0.75 mg) were similar to those seen in intravenous ondansetron 32 mg recipients in a randomised, double-blind trial. Intravenous palonosetron was generally well tolerated in clinical trials, with few adverse events being treatment related. Palonosetron had no significant effect on the corrected QT interval or laboratory parameters.

Topics: Antiemetics; Antineoplastic Agents; Humans; Injections, Intravenous; Isoquinolines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Randomized Controlled Trials as Topic; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Palonosetron, a highly selective and potent 5-HT(3) receptor antagonist with a strong binding affinity and a long plasma elimination half-life (approximately 40 hours), has shown efficacy in Phase II trials in preventing chemotherapy-induced nausea and vomiting (CINV) resulting from highly emetogenic chemotherapy. The current Phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed CINV after moderately emetogenic chemotherapy.. In the current study, 592 patients were randomized to receive a single, intravenous dose of palonosetron 0.25 mg, palonosetron 0.75 mg, or dolasetron 100 mg, 30 minutes before receiving moderately emetogenic chemotherapy. The primary efficacy endpoint was the proportion of patients with a complete response (CR; defined as no emetic episodes and no rescue medication) during the first 24 hours after chemotherapy. Secondary endpoints included assessment of prevention of delayed emesis (2-5 days postchemotherapy).. In the current study, 569 patients received study medication and were included in the intent-to-treat efficacy analyses. CR rates during the first 24 hours were 63.0% for palonosetron 0.25 mg, 57.1% for palonosetron 0.75 mg, and 52.9% for dolasetron 100 mg. CR rates during the delayed period (24-120 hours after chemotherapy) were superior for palonosetron compared with dolasetron. Adverse events (AEs) were mostly mild to moderate and not related to study medication, with similar incidences among groups. There were no serious drug-related AEs.. A single dose of palonosetron is as effective as a single dose of dolasetron in preventing acute CINV and superior to dolasetron in preventing delayed CINV after moderately emetogenic chemotherapy, with a comparable safety profile for all treatment groups.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Double-Blind Method; Female; Humans; Indoles; Infusions, Intravenous; Isoquinolines; Male; Middle Aged; Neoplasms; Palonosetron; Quinolizines; Quinuclidines; Severity of Illness Index; Treatment Outcome; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a recognized adverse outcome among patients with cancer. This retrospective study aimed to quantify the treatment outcomes, resource utilization, and costs associated with antiemetic use to prevent CINV in a broad US population who received cisplatin-based chemotherapy.. Data from the STATinMED RWD Insights Database was collected from January 1, 2015 to December 31, 2020. Cohorts included any patients that had at least one claim for fosnetupitant + palonosetron (NEPA) or fosaprepitant + palonosetron (APPA) and evidence of initiating cisplatin-based chemotherapy. Logistic regression was used to evaluate nausea and vomiting visits within 14 days after chemotherapy, and generalized linear models were used to examine all-cause and CINV-related healthcare resource utilization (HCRU) and costs.. NEPA was associated with significantly lower rates of nausea and vomiting visits after chemotherapy (p = 0.0001), including 86% greater odds of nausea and vomiting events for APPA during the second week after chemotherapy (odds ratio [OR] = 1.86; p = 0.0003). The mean numbers of all-cause inpatient visits (p = 0.0195) and CINV-related inpatient and outpatient visits were lower among NEPA patients (p < 0.0001). These differences corresponded to 57% of NEPA patients and 67% of APPA patients having one or more inpatient visits (p = 0.0002). All-cause outpatient costs and CINV-related inpatient costs were also significantly lower for NEPA (p < 0.0001). The mean number of all-cause outpatient visits, all-cause inpatient costs, and CINV-related outpatient costs was not significantly different between groups (p > 0.05).. In this retrospective study based on claims data, NEPA was associated with lower rates of nausea and vomiting and lower CINV-related HCRU and costs compared to APPA following cisplatin-based chemotherapy. These results complement clinical trial data and published economic models supporting the use of NEPA as a safe, effective, and cost-saving antiemetic for patients undergoing chemotherapy.

Topics: Antiemetics; Antineoplastic Agents; Cisplatin; Delivery of Health Care; Gastrointestinal Agents; Humans; Nausea; Neoplasms; Palonosetron; Quinuclidines; Retrospective Studies; Treatment Outcome; Vomiting

Topics: Antineoplastic Agents; Dexamethasone; Humans; Nausea; Neoplasms; Palonosetron; Quinuclidines; Vomiting

A triple antiemetic therapy combining aprepitant (APR) with conventional double antiemetic therapy, including 5-hydroxytryptamine 3 receptor antagonist (5-HT₃-RA) and dexamethasone (DEX), is recommended for preventing chemotherapy-induced nausea and vomiting induced by a carboplatin (CBDCA) regimen. However, consensus on the additive effects of APR for gynecological patients on a combined regimen of paclitaxel and CBDCA (TC regimen) has yet to be reached. This retrospective study investigated the antiemetic effects of palonosetron and DEX (PD therapy) and granisetron and DEX with APR (GDA therapy) in patients with gynecologic cancer and who underwent their first TC regimen cycle between April 2017 and March 2020 at the Gunma University Hospital Outpatient Chemotherapy Center. The results showed that the complete response rate of the 92 patients who underwent PD therapy (PD group) and the 46 patients who underwent GDA therapy (GDA group) were both 80.4% (p = 1.000), and the complete control rates of the PD and GDA groups were 78.3% and 80.4%, respectively (p = 0.828), resulting in no significant difference. Furthermore, we observed no significant difference between the PD and GDA groups in the incidence of grade ≥2 nausea, vomiting, and anorexia (nausea: 7.6% vs. 0%, p = 0.095; vomiting: 4.3% vs. 0%, p = 0.301; and anorexia: 9.8% vs. 2.2%, p = 0.164). Concerning adverse events, compared to the PD group, the GDA group showed significantly higher incidence of grade ≥2 malaise (7.6% vs. 19.6%, p = 0.039). Given the lack of difference in the antiemetic effects of PD and GDA therapies, antiemetic therapy should be selected carefully for individual patients by accounting for the incidence of adverse reactions and interactions with APR.

Topics: Anorexia; Antiemetics; Aprepitant; Carboplatin; Dexamethasone; Female; Granisetron; Humans; Nausea; Neoplasms; Paclitaxel; Palonosetron; Retrospective Studies; Vomiting

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Middle Aged; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Ondansetron; Palonosetron; Retrospective Studies; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) can be a serious and debilitating adverse effect that is highly feared by cancer patients. For patients receiving moderately emetogenic chemotherapy regimens at our institution in the ambulatory infusion center, palonosetron was selected as the preferred serotonin (5-HT3) antagonist for CINV prophylaxis per the 2016 NCCN Guidelines, when a neurokinin1 antagonist was not included in the prophylactic regimen. The purpose of this study was to evaluate the efficacy of dexamethasone and palonosetron versus granisetron for the prevention of CINV in patients receiving moderately emetogenic chemotherapy regimens.. This study is an Institutional Review Board-approved, single-center retrospective review of electronic health records including patients who received moderately emetogenic chemotherapy regimens with CINV prophylaxis with dexamethasone and either palonosetron or granisetron.. Despite palonosetron's better efficacy, longer half-life, and higher binding affinity, the results of this retrospective review demonstrates that the choice of serotonin antagonist, palonosetron or granisetron, did not result in a change in day 1 intravenous prophylactic antiemetics or antiemetic outpatient medications for patients undergoing moderately emetogenic chemotherapy regimens.

Topics: Academic Medical Centers; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Female; Granisetron; Humans; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Retrospective Studies; Serotonin 5-HT3 Receptor Antagonists; Vomiting; Young Adult

NEPA is the first fixed-combination antiemetic composed of the neurokinin-1 receptor antagonist netupitant (netupitant; 300 mg) and the 5-hydroxytryptamine-3 receptor antagonist palonosetron (palonosetron; 0.50 mg). This study evaluated the pharmacokinetic profiles of netupitant and palonosetron. The pharmacokinetic profiles of both drugs were summarized using data from phase 1-3 clinical trials. netupitant and palonosetron have high absolute bioavailability (63%-87% and 97%, respectively). Their overall systemic exposures and maximum plasma concentrations are similar under fed and fasting conditions. netupitant binds to plasma proteins in a high degree (>99%), whereas palonosetron binds to a low extent (62%). Both drugs have large volumes of distribution (cancer patients: 1656-2257 L and 483-679 L, respectively). netupitant is metabolized by cytochrome P450 3A4 to 3 major pharmacologically active metabolites (M1, M2, and M3). palonosetron is metabolized by cytochrome P450 2D6 to 2 major substantially inactive metabolites (M4 and M9). Both drugs have similar intermediate-to-low systemic clearances and long half-lives (cancer patients: netupitant, 19.5-20.8 L/h and 56.0-93.8 hours; palonosetron: 7.0-11.3 L/h and 43.8-65.7 hours, respectively). netupitant and its metabolites are eliminated via the hepatic/biliary route (87% of the administered dose), whereas palonosetron and its metabolites are mainly eliminated via the kidneys (85%-93%). Altogether, these data explain the lack of pharmacokinetic interactions between netupitant and palonosetron at absorption, binding, metabolic, or excretory level, thus highlighting their compatibility as the oral fixed combination NEPA, with administration convenience that may reduce dosing mistakes and increase treatment compliance.

Topics: Antiemetics; Antineoplastic Agents; Biological Availability; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Combinations; Humans; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Palonosetron; Pyridines; Vomiting

Chemotherapy-induced nausea and vomiting diminishes quality of life and increases healthcare resource use. This retrospective medical records analysis evaluated hydration requirements with emetogenic chemotherapy.. Cancer patients received moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC), and antiemetics palonosetron or granisetron extended-release subcutaneous (GERSC), neurokinin 1 receptor antagonist and dexamethasone. Unscheduled hydration event rates were determined.. For 186 patients (92 palonosetron, 94 GERSC) overall, mean hydration rate was significantly higher with palonosetron (0.6 vs 0.2; p = 0.0005). Proportion of patients with ≥1 hydration event was significantly higher with palonosetron overall (54 vs 33%; p = 0.0033) and in cycles 2-4 and the HEC subgroup.. GERSC within a three-drug antiemetic regimen may reduce unscheduled hydration requirements with MEC or HEC.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Delayed-Action Preparations; Dexamethasone; Female; Fluid Therapy; Granisetron; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Palonosetron; Retrospective Studies; Serotonin 5-HT3 Receptor Antagonists; Vomiting; Young Adult

Nausea is more difficult to control than vomiting in chemotherapy. We therefore analyzed the efficacy of a strong supportive treatment with aprepitant, palonosetron, and dexamethasone against nausea for various moderately emetogenic chemotherapy (MEC).. A total of 312 cases treated by palonosetron with or without aprepitant receiving MEC regimens using oxaliplatin, carboplatin, and irinotecan from 2014 to 2016 in our outpatient center for digestive organ cancers, lung cancers, and gynecological cancers were analyzed. Through propensity score matching analysis, cases were divided into 97 cases receiving 2 drugs (palonosetron+dexamethasone) and 97 receiving 3 drugs (aprepitant+palonosetron+dexamethasone). We examined the control rates of nausea for the first two consecutive courses in the both groups. Additionally, risk factors for acute and delayed nausea were analyzed using a multivariate analysis among overall 312 cases.. The control rates of nausea in the two- and the three-drug groups were as follows: acute, 92.8 and 95.9% (p = 0.35); and delayed, 83.5 and 81.4% (p = 0.85), although the control rates of vomiting exceeded 95% in both groups. A multivariate analysis showed that significant risk factors for acute nausea (odds ratio, 95% confidence interval) were elevation of serum creatinine (12.601, 2.437-65.157), general fatigue (3.728, 1.098-12.661), and performance status (PS) 2 (19.829, 3.200-122.865). The significant risk factors for delayed nausea were elevation of alanine aminotransferase (2.397, 1.153-4.984), general fatigue (2.652, 1.380-5.097), and PS 2 (5.748, 1.392-23.740).. The control for nausea in MEC was insufficient even with palonosetron and aprepitant, and we should pay attention to risk factors for preventing nausea.

Topics: Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Treatment Outcome

Chemotherapy-induced nausea and vomiting (CINV) can be prevented in most patients receiving appropriate antiemetic treatment. However, inadequate uptake of current antiemetic guideline recommendations by physicians, and poor treatment adherence by patients, lead to suboptimal CINV control. There is an unmet need to optimize guideline-consistent use of antiemetics to improve CINV management and prevention. Herein, we provide an overview of CINV, then discuss oral and intravenous NEPA, the first fixed combination antiemetic, composed of netupitant/fosnetupitant and palonosetron. We describe the main pharmacologic and pharmacokinetic characteristics of NEPA, and review the clinical evidence supporting its use in the prevention of CINV.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Humans; Nausea; Neoplasms; Palonosetron; Practice Guidelines as Topic; Prognosis; Pyridines; Vomiting

Younger age and female sex have already been well-known risk factors for chemotherapy-induced nausea and vomiting (CINV), and 30-50% of cancer patients still suffer from CINV. Genetic polymorphisms are suggested to influence antiemetic treatment response.. This study included a subset of patients previously enrolled in a randomised controlled trial; 156 patients were evaluated. This study aimed to evaluate the role of pharmacogenomic polymorphisms relevant to antiemetic response in patients with cancer receiving cisplatin-based chemotherapy. The study's efficacy endpoint was the proportion of patients with complete response (CR). The study endpoint was evaluated separately in the acute (CR. Multivariate logistic regression analysis revealed that the ERCC1 8092AA (odds ratio [OR] = 11.25; 95% confidence interval [CI] 1.74-72.71; p = 0.011) and female sex (OR = 3.63; 95% CI 1.14-11.58; p = 0.029) were significant predictors of CR. ERCC1 polymorphism influenced the extent of CINV control in patients receiving cisplatin-based chemotherapy.. Clinical trial information: UMIN 000009335.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase III as Topic; Dexamethasone; Female; Genetic Predisposition to Disease; Granisetron; Humans; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Polymorphism, Single Nucleotide; Randomized Controlled Trials as Topic; Vomiting

This retrospective analysis evaluated chemotherapy-induced nausea and vomiting (CINV)-related hydration needs with palonosetron or granisetron extended-release subcutaneous (GERSC), approved in 2016 for CINV prevention.. At a community practice, CINV-related hydration per chemotherapy cycle was determined following highly (HEC) or moderately emetogenic chemotherapy (MEC) and a guideline-recommended antiemetic regimen: NK-1 receptor antagonist, dexamethasone and either palonosetron only, GERSC only, or palonosetron switched to GERSC.. Palonosetron-only patients (n = 93) had a significantly higher mean (standard deviation) hydration rate (0.9 [1.1]) than GERSC-only patients (n = 91; 0.3 [0.6]; p < 0.0001). Switched patients' (n = 48) hydration rates were significantly higher in the HEC subgroup with palonosetron (0.7 [1.2]) versus GERSC (0.5 [1.0]; p = 0.028).. GERSC in a three-drug antiemetic regimen may reduce hydration needs following HEC or MEC. [Formula: see text].

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Delayed-Action Preparations; Dexamethasone; Female; Fluid Therapy; Granisetron; Humans; Injections, Subcutaneous; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Practice Guidelines as Topic; Quinuclidines; Retrospective Studies; Serotonin Antagonists; Treatment Outcome; Vomiting

Palonosetron is an effective antiemetic in chemotherapy-induced nausea and vomiting (CINV), but has yet to be studied in the radiation setting. The purpose of the present study was to investigate the efficacy and safety of palonosetron in the prophylaxis of radiation-induced nausea and vomiting (RINV).. Patients without existing nausea and vomiting undergoing palliative radiotherapy to sites with emetic risk were prescribed palonosetron 0.5 mg orally before the start of radiation treatment, and every other day until completion of treatment. Patients were followed up in acute (day 1 of treatment to day 1 after treatment) and delayed phases (days 2-10 after treatment). The primary endpoint was control of vomiting. Complete control was defined as no use of rescue medication and no episodes of nausea or vomiting. Secondary endpoints included control of nausea and quality of life (QOL). QOL was assessed with the Functional Living Index-Emesis and the European Organisation for Research and Treatment of Cancer QOL Questionnaire-Core 15 Palliative (C15-PAL).. In all evaluable patients (n=75), complete control of vomiting was 93.3% in the acute phase and 93.2% in the delayed phase. Complete control of nausea was 74.7% in the acute phase and 74.0% in the delayed phase.. Results suggest improved control in RINV compared to historical reports with first generation serotonin receptor antagonists (RA). A randomized study will be needed to confirm this finding.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Pilot Projects; Quinuclidines; Radiotherapy; Serotonin Antagonists; Vomiting

Approved almost 15 years ago for use in the chemotherapy setting, palonosetron, a 2nd generation 5-hydroxtryptamine 3 receptor antagonist (5-HT3 RA), has demonstrated efficacy in preventing chemotherapy-induced nausea and vomiting. However, its utility in the prophylaxis and treatment of radiation-induced nausea and vomiting (RINV) has yet to be evaluated. In this pilot study, we investigated the rates of control in RINV in patients with pre-existing emesis.. Patients with pre-existing emesis undergoing palliative radiotherapy to sites with emetic risk were prescribed palonosetron 0.5 mg before the start of radiation treatment, and every other day until completion of treatment. Patients were followed up in acute (day 1 of treatment to day 1 after treatment) and delayed phases (days 2-10 after treatment). Prophylaxis and rescue (PR) was defined as a decrease in anti-emetic use, or episodes of nausea and/or vomiting from baseline. Complete prophylaxis (CP) was defined as no increase in anti-emetic use, or episodes of nausea and/or vomiting. Secondary endpoints included control of nausea and quality of life (QOL), as assessed with the Functional Living Index-Emesis and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15 Palliative.. Fourteen patients were enrolled. Rates of control were higher in the acute phase (n=14) for nausea (PR =42.9%, CP =42.9%) and vomiting (PR =21.4%, CP =71.4%) compared to the delayed phase (n=13) for nausea (PR =42.9%, CP =7.7%) and vomiting (PR =15.4%, CP =53.8%).. Palonosetron appears to be safe and patients with pre-existing emesis receiving palliative radiotherapy. More studies are needed to investigate its efficacy in this patient population.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antiemetics; Female; Humans; Male; Middle Aged; Neoplasms; Palliative Care; Palonosetron; Pilot Projects; Quality of Life; Surveys and Questionnaires; Vomiting

The purpose of this study was to evaluate the efficacy of combined treatment with the long-acting 5-hydroxytryptamine receptor-3 antagonist, palonosetron, the neurokinin-1 receptor antagonist, oral aprepitant, and dexamethasone as primary antiemetic prophylaxis for cancer patients receiving highly emetogenic cisplatin-based chemotherapy.. Chemotherapy-naïve patients received the triple combination of palonosetron (0.25 mg), aprepitant (125 mg on day 1 and 80 mg on days 2 and 3), and dexamethasone (20 mg) from the beginning of highly emetogenic chemotherapy with cisplatin-based (≥50 mg/m(2)) regimens. The primary endpoint was a complete response (no emetic episodes and no rescue antiemetics) during the days 1-6.. Sixty-nine hospitalized patients receiving chemotherapy from September 2012 to October 2014 were analyzed. Complete response of vomiting and nausea-free was achieved in 97.1% and 85.5% of patients in the first cycle, respectively, and 96.7% and 83.6% of patients in the second cycle, respectively. Common adverse events in all 69 patients included constipation (43%), hiccup (26%), and headache (4%).. The combination of palonosetron, aprepitant, and dexamethasone as primary antiemetic prophylaxis for cancer patients with highly emetogenic cisplatin-based chemotherapy is effective.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Treatment Outcome; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. The first generation 5-HT3 receptor antagonists have been very effective in the control of chemotherapy induced emesis in the first 24 h postchemotherapy (acute emesis), but have not been as effective against delayed emesis (24-120 h postchemotherapy). Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists appears to be the most effective agent in its class. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a FDA approved antipsychotic that blocks multiple neurotransmitters: dopamine at D1, D2, D3, D4 brain receptors, serotonin at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors, has emerged in recent trials as an effective preventative agent for chemotherapy-induced emesis and nausea, as well as a very effective agent for the treatment of breakthrough emesis and nausea. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Dexamethasone; Half-Life; Humans; Isoquinolines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Quality of Life; Quinuclidines; Receptors, Neurokinin-1; Receptors, Serotonin, 5-HT3; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Nausea and vomiting are among adverse effects of chemotherapy that significantly worsen quality of life of patients. 5-HT3 receptor antagonists have been used in recent decades to prevent and arrest these complications. Palonosetron is the most modern drug in this group. Palonosetron application during highly and moderately emetogenic chemotherapy showed its high effectiveness for nausea and vomiting prevention.

Topics: Antiemetics; Antineoplastic Agents; Humans; Isoquinolines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Severity of Illness Index; Treatment Outcome; Vomiting

Antiemetic triplet therapy including dexamethasone (DEX) is widely used for patients receiving highly emetogenic chemotherapy (HEC). In Japan, the appropriate dose of DEX has not been established for this combination.. To assess the efficacy and safety of increased-dose DEX, we retrospectively examined patients receiving HEC with antiemetic triplet therapy.. Twenty-four patients (fosaprepitant group) were given an increased-dose of DEX (average total dose: 45.8mg), fosaprepitant, and 5-HT3 antagonist. A lower-dose of DEX (33.6mg), oral aprepitant, and 5-HT3 antagonist were administered to the other 48 patients (aprepitant group). The vomiting control rates in the fosaprepitant and aprepitant groups were 100% and 85.4% in the acute phase, and were 75.0% and 64.6% in the delayed phase. The incidences of toxicity were similar comparing the two groups.. Triplet therapy using an increased-dose of DEX is suggested to be safe and effective for patients receiving HEC.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Benzimidazoles; Dexamethasone; Drug Therapy, Combination; Female; Granisetron; Humans; Isoquinolines; Japan; Male; Middle Aged; Morpholines; Neoplasms; Palonosetron; Quinuclidines; Retrospective Studies; Serotonin Antagonists; Vomiting

A quality improvement project was implemented to improve adherence to evidence-based antiemetic guidelines for malignant glioma patients treated with moderately emetic chemotherapy (MEC). Poorly controlled chemotherapy-induced nausea and vomiting (CINV) reduce cancer treatment efficacy and significantly impair cancer patients' quality of life (QOL). A review of Duke University Preston Robert Tisch Brain Tumor Center (PRTBTC)'s usual practice demonstrates a high incidence (45%) of CINV, despite premedication with short-acting 5-HT3-serotonin-receptor antagonists (5-HT3-RAs). National Comprehensive Cancer Network (NCCN)'s evidence-based guidelines recommend the combination of the long-acting 5-HT3-RA palonosetron (PAL) and dexamethasone (DEX) for the prevention of acute and delayed CINV with MEC. Low adherence (58%) to antiemetic guidelines may have explained our high CINV incidence.. One-sample binomial test, quasi-experimental design, evaluated a combination intervention that included a provider education session; implementation of risk-assessment tool with computerized, standardized antiemetic guideline order sets; and a monthly audit-feedback strategy. Post-implementation adherence to evidence-based antiemetic order sets and patient outcomes were measured and compared to baseline and historical data. Primary outcome was the guideline order set adherence rate. Secondary outcomes included nausea/vomiting rates and QOL.. Adherence to ordering MEC guideline antiemetics increased significantly, from 58% to a sustained 90%, with associated improvement in nausea/vomiting. In acute and delayed phases, 75 and 84% of patients, respectively, did not experience CINV. There was no significant change in QOL.. Combination intervention and audit-feedback strategy to translate evidence into oncology practice improved and sustained adherence to antiemetic guidelines. Adherence corresponded with effective nausea/vomiting control and preserved QOL in patients with malignant gliomas.

Topics: Adult; Antiemetics; Antineoplastic Agents; Brain Neoplasms; Dexamethasone; Female; Glioblastoma; Humans; Isoquinolines; Male; Medication Adherence; Middle Aged; Nausea; Neoplasms; Palonosetron; Quality of Life; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Translational Research, Biomedical; Treatment Outcome; Vomiting

The aims of this study were to evaluate the safety, efficacy, and pharmacokinetics of repeated doses of palonosetron 0.75 mg on days 1 and 3 in Japanese patients who received highly or moderately emetogenic chemotherapy.. Twenty- six patients received palonosetron 0.75 mg intravenously before chemotherapy on days 1 and 3 plus dexamethasone (12-16 mg before chemotherapy on day 1 and 4-8 mg on days 2 and 3). The primary endpoints were safety and pharmacokinetics. Pharmacokinetics were evaluated in a subset of patients (n=6). Complete response and complete protection were evaluated as secondary endpoints.. The accumulation ratios for C max and AUClast after the second dose on day 3 were 1.42 and 1.37, respectively. These values were consistent with the theoretical values expected from the half-life of palonosetron on day 1. Almost all of the patients had no nausea or vomiting in the acute phase (complete response (CR) rate, 96.2% [25/26]; CP rate, 92.3% [24/26]). In the delayed phase (24-192 h post-chemotherapy), the complete response and complete protection rates were 76.9% (20/26) and 61.5% (16/26), respectively. Treatment was well tolerated.. This is the first study to report the pharmacokinetics of multiple doses of palonosetron 0.75 mg, given on days 1 and 3, in Japanese patients. Repeated treatment with palonosetron was safe and well tolerated by patients who received highly or moderately emetogenic anticancer chemotherapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Dexamethasone; Female; Humans; Injections, Intravenous; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin Antagonists; Vomiting

Nausea and vomiting are among the most problematic symptoms experienced by patients with cancer who are receiving chemotherapy. 5-hydroxytryptamine 3(5-HT3)-receptor antagonists, NK1 receptor antagonists(aprepitant)and dexamethasone are now the standard therapies for preventing chemotherapy-induced nausea and vomiting(CINV)that follow highly emetogenic chemotherapy, such as cisplatin and anthracycline. However, since it is not cleared which 5-HT3-recepter antagonist is a proper treatment for combined use with aprepitant and dexamethasone, we conducted a questionnaire survey, which used the numerical rating scale(NRS), for comparing palonosetron with granisetron in the same patient. Palonosetron showed a significant improvement of nausea for both acute(within 24 hours)and delayed phase(24-120 hours later), regardless of the type of chemotherapy(cisplatin or anthracycline-based regimen). Furthermore, palonosetron had a tolerable safety profile. Our study suggests that palonosetron-based antiemetic treatment will be a preferred choice for preventing CINV following highly emetogenic chemotherapy.

Topics: Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Drug Combinations; Female; Granisetron; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Retrospective Studies; Risk; Vomiting

Palonosetron is a novel 5-hydroxytryptamine(3) (5 HT(3)) receptor antagonist, which has been shown to be superior to first generation 5 HT(3) receptor antagonists regarding the prevention of acute, delayed and overall chemotherapy-induced nausea and vomiting. First generation 5 HT(3) receptor antagonists may induce electrocardiographic changes of heart rate and repolarization. The acute cardiac effect of palonosteron is unknown. The purpose of this study is to determine acute effects of palonosetron on electrocardiographic (ECG) parameters in cancer patients.. The study had a prospective design. Seventy-six cancer patients with normal cardiac function who received palonosetron for prevention of chemotherapy-induced nausea and vomiting were enrolled. Standard 12-lead ECG recordings were performed at baseline and 30 min after palonosetron administration. P wave durations and corrected QT intervals were measured; P wave dispersion (Pd) and QTc dispersion were calculated.. Median heart rate did not differ among 76 patients enrolled before and after palonosetron administration (p: 0.6). Systolic and diastolic blood pressures were not significantly different before and after palonosteron (p values 0.9 and 0.3, respectively). Although median QT min value was higher after palonosetron administration than before palonosetron administration, the difference was not statistically significant (p: 0.6).. Palonosetron seems to have no acute arrhythmogenic potential.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Electrocardiography; Heart Rate; Humans; Isoquinolines; Middle Aged; Nausea; Neoplasms; Palonosetron; Prospective Studies; Quinuclidines; Serotonin Antagonists; Vomiting; Young Adult

To evaluate the efficacy and toxicity of palonosetron for prevention of vomiting induced by high dose cisplatin-based chemotherapy.. One-hundred and twenty-eight patients received tropisetron 5 mg plus dexamethasone 10 mg at the first cycle or palonosetron 0.25 mg plus dexamethasone 10 mg, respectively, each administered 30 min before the initiation of high dose cisplatin-based chemotherapy. To observe the remission rate of acute emetic episodes and delayed emetic episodes, adverse effects and daily food-intake in the patients after the chemotherapy.. The complete response (CR) rates for acute vomiting were not significantly different between the tropisetron and palonosetron cycles (75.8% vs. 79.7%, P>0.05). The complete control rate of delayed vomiting in the palonosetron cycle was significantly higher than that in the tropisetron cycle (70.3% vs. 50.8%, P<0.01). The food-intake decrease rate of palonosetron cycle was 18.8%, significantly lower than the 53.1% of the tropisetron cycle (P<0.05). The toxicity in the two cycles was similar and no grade 3-4 toxicity was observed.. Palonosetron is superior to tropisetron with a lower remission rate of delayed emesis induced by high dose cisplatin-based chemotherapy and with tolerable toxicity. Moreover, the apparent emesis control of palonosetron treatment seems to provide an adequate food-intake in these patients.

Topics: Aged; Antiemetics; Antineoplastic Agents; Cisplatin; Eating; Female; Humans; Indoles; Isoquinolines; Male; Middle Aged; Neoplasms; Palonosetron; Quinuclidines; Tropisetron; Vomiting

Despite favorable evidence from clinical trials for single-dose palonosetron versus other commercially available 5-HT(3)-receptor antagonists for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV), clinical comparative data are scarce from hospital outpatient settings, where these antiemetic agents are used in patients diagnosed with cancer who are receiving chemotherapy (CTH).. The purpose of our retrospective study was to assess the hospital claims to evaluate the rate of uncontrolled CINV with antiemetic prophylaxis using palonosetron versus other 5-HT(3)-receptor antagonists in patients diagnosed with cancer who are receiving CTH (highly emetogenic CTH, moderately emetogenic CTH, low-emetogenic CTH, or minimally emetogenic CTH) treatment in a hospital outpatient setting.. Patients aged ≥18 years who had cancer and were being treated with CTH and antiemetic prophylaxis with palonosetron (Group 1) and other 5-HT(3) receptor antagonists (Group 2) for the first time between April 1, 2007, and March 31, 2009, were identified using a hospital-service database. Within each CTH cycle, CINV events were identified through International Classification of Diseases (ICD)-9 codes for nausea, vomiting, and/or volume depletion (from Day 1 of each CTH administration until the end of the CTH cycle) or for use of rescue medications (Day 2 until the end of the CTH cycle). A multivariate regression model was developed to predict uncontrolled CINV event rates per CTH cycle between Groups 1 and 2 matched on CTH emetogenicity distribution in the study follow-up period (first of 8 cycles or 6 months). A subgroup analysis of patients on CTH with the highest risk of nausea and vomiting (highly emetogenic CTH or moderately emetogenic CTH) was also conducted.. Of 9144 identified patients, 1775 were prescribed palonosetron (Group 1). Group 1 patients were statistically younger (61.2 vs 62.8 years; P < 0.001), composed of more females (57.1% vs 51.9%; P < 0.001) and more whites (72.8% vs 71.4%; all races P < 0.001), received more highly emetogenic CTH treatments (43.3% vs 28.5%; all CTH P < 0.001), and had more lung (26.1% vs 22.4%) and breast cancer patients (19.3% vs 15.3%; all cancer P < 0.001). The regression model predicted a 13.7% decrease in CINV event rate per CTH cycle for Group 1 versus Group 2. For Subgroup 1, the model predicted a 12.5% decrease in the CINV event rate per cycle in Group 1 patients versus those in Group 2.. In this study, patients with cancer who were treated with CTH and on antiemetic prophylaxis using palonosetron were found to have significantly lower CINV event rates than those receiving other 5-HT(3) receptor antagonists.

Topics: Adolescent; Aged; Antiemetics; Antineoplastic Agents; Databases, Factual; Female; Follow-Up Studies; Humans; Isoquinolines; Male; Middle Aged; Multivariate Analysis; Nausea; Neoplasms; Outpatient Clinics, Hospital; Palonosetron; Quinuclidines; Regression Analysis; Retrospective Studies; Serotonin 5-HT3 Receptor Antagonists; Vomiting; Young Adult

Topics: Adolescent; Antiemetics; Bone Marrow Transplantation; Child; Child, Preschool; Female; Humans; Infant; Isoquinolines; Male; Nausea; Neoplasms; Palonosetron; Quinuclidines; Retrospective Studies; Serotonin Antagonists; Vomiting

Palonosetron is a new generation 5-HT3-receptor antagonist with a significantly prolonged half-life and a once-a-day administration compared to the conventional setrons. To evaluate the antiemetic efficacy of palonosetron in the daily hospital practice setting, a postmarketing study was carried out in Austria.. Palonosetron was administered at 0.25 mg on day 1 of each cycle to 135 cancer patients who received moderately or highly emetogenic chemotherapy either as an IV bolus or as a short-term infusion. Two thirds of these patients were females (n = 90), the majority had breast cancer (n = 38) and the majority received cisplatin, carboplatin, anthracyclines, 5-fluorouracil or cyclophosphamide.. The complete antiemetic response rate was 68 % overall with 87 % efficacy on day 1 and 72 % efficacy on days 2 to 5. Higher antiemetic response was achieved in male patients, in patients being aged > or = 50 years, and in chemonaive patients. Twenty-four percent of patients needed rescue medication. Only 1.5 % of patients reported mild adverse events.. Palonosetron resulted in high antiemetic efficacy in this study. Female gender and age < or = 50 years should be particularly considered when the antiemetic regimen is selected.

Topics: Adult; Age Factors; Aged; Antiemetics; Antineoplastic Agents; Austria; Breast Neoplasms; Cancer Care Facilities; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Practice Guidelines as Topic; Product Surveillance, Postmarketing; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Sex Factors; Surveys and Questionnaires; Time Factors; Vomiting

The 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists have become the cornerstone for preventing and treating chemotherapy-induced nausea and vomiting. Four 5-HT3 antagonists are commercially available in the United States, and numerous reports have been published comparing 2 or more agents. The studies ranged from randomized, double-blinded to open-label or retrospective trials; included chemotherapy-naïve and -non-naïve patients; and covered a range of doses and routes of administration with and without concomitant steroids, for preventing and treating nausea and vomiting after highly and moderately high emetogenic chemotherapy. With few exceptions, the studies uniformly show an equivalent efficacy rate and side effect profile among the various agents at equivalent doses. This article reviews the pharmacology of the class for insight into minor differences among the agents that could possibly influence drug selection for certain patients, and considers data on the absorption, half-life, metabolism, and receptor activity. Clinical trials support the claim of various guidelines that the 5-HT3 receptor antagonists are therapeutically similar in safety and efficacy, particularly because the current best practice for preventing nausea and vomiting after highly and moderately high emetogenic chemotherapy is a combination of a 5-HT3 antagonist, steroids, and aprepitant.

Topics: Humans; Indoles; Isoquinolines; Nausea; Neoplasms; Ondansetron; Palonosetron; Quinolizines; Quinuclidines; Randomized Controlled Trials as Topic; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Therapeutic Equivalency; Vomiting

Topics: Administration, Oral; Anorexia; Antiemetics; Antineoplastic Agents; Aprepitant; Asthenia; Constipation; Diarrhea; Drug Interactions; Dyspepsia; Fatigue; Fever; Granisetron; Headache; Hiccup; Humans; Indoles; Injections, Intravenous; Isoquinolines; Morpholines; Nausea; Neoplasms; Ondansetron; Palonosetron; Quinolizines; Quinuclidines; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Comprehensive Health Care; Evidence-Based Medicine; Humans; Isoquinolines; Models, Organizational; Morpholines; Nausea; Neoplasms; Nurse's Role; Oncology Nursing; Palonosetron; Patient Care Team; Practice Guidelines as Topic; Quinuclidines; Total Quality Management; Vomiting

Effective antiemetic therapy is crucial for patients undergoing chemotherapy or radiotherapy for cancer. Severe nausea and vomiting associated with such cancer treatment can lead to anxiety, anorexia, dehydration, electrolyte disturbance and renal failure, and may interrupt cancer therapy, demoralise patients or even cause them to abandon treatment. In 1992, we welcomed the introduction of ondansetron, the first selective serotonin type 3- (5HT3-) receptor antagonist marketed in the UK, as an important advance in preventing chemotherapy-induced nausea and vomiting. Several selective 5HT3-receptor antagonists are now licensed. They are widely prescribed to patients receiving cancer treatment, but not always appropriately. Here we review their optimal use.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Child; Granisetron; Humans; Indoles; Isoquinolines; Nausea; Neoplasms; Ondansetron; Palonosetron; Practice Guidelines as Topic; Quinolizines; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Tropisetron; Vomiting

Topics: Antiemetics; Clinical Trials as Topic; Drug Administration Schedule; Humans; Infusions, Intravenous; Isoquinolines; Nausea; Neoplasms; Ondansetron; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Humans; Isoquinolines; Male; Neoplasms; Palliative Care; Palonosetron; Quinuclidines; Vomiting