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Journal of Pharmaceutical Health Care... Aug 2022Cisplatin (CDDP)-induced nephrotoxicity is the most important complication of CDDP treatment. 5-Hydroxytryptamine type 3 receptor antagonists (5-HTRAs) are widely used...
BACKGROUND
Cisplatin (CDDP)-induced nephrotoxicity is the most important complication of CDDP treatment. 5-Hydroxytryptamine type 3 receptor antagonists (5-HTRAs) are widely used to prevent chemotherapy-induced nausea and vomiting (CINV). However, in patients with the triple antiemetic (neurokinin-1 receptor antagonist, 5-HTRA, and dexamethasone) therapy, the advantage of palonosetron in comparison with other 5-HTRAs on CDDP-induced nephrotoxicity and CINV remains unclear. In the present study, we investigated the effect of palonosetron on CDDP-induced nephrotoxicity and CINV in patients with the triple antiemetic therapy by a retrospective cohort study and a pharmacovigilance analysis.
METHODS
We retrospectively analyzed the effect of 5-HTRAs on the development of nephrotoxicity and CINV in 110 patients who received CDDP, fluorouracil, and triple antiemetic therapy for the treatment of esophageal cancer. Moreover, the effect of 5-HTRAs on CDDP-induced nephrotoxicity was validated in patients with the triple antiemetic therapy using the Japanese Adverse Drug Event Report (JADER) database.
RESULTS
In a retrospective study, the incidence of nephrotoxicity (≥ grade 1) in patients receiving palonosetron (18%) was significantly lower than that in patients receiving ramosetron (another 5-HTRA) (36%, p = 0.044). Moreover, severe nephrotoxicity ≥ grade 3 was observed in one patient treated with ramosetron, whereas hematological toxicity was comparable between the two groups (p = 0.553). Furthermore, the incidence rate of CINV within 120 h following CDDP administration in patients treated with palonosetron (18%) was significantly lower than that in patients receiving ramosetron (39%, p = 0.026). JADER database analyses revealed that the reporting odds ratio of palonosetron for CDDP-induced acute kidney injury was 0.282 (95% confidence interval: 0.169-0.472).
CONCLUSIONS
The findings of the present study suggested a greater potential of palonosetron against CDDP-induced nephrotoxicity and CINV than other 5-HTRAs in patients with the triple antiemetic therapy.
PubMed: 35909131
DOI: 10.1186/s40780-022-00252-z -
Anesthesia, Essays and Researches 2022Postoperative nausea and vomiting (PONV) are one of the common distressing conditions after anesthesia. The PONV are related to several potential risk factors are...
Comparison of Palonosetron Versus Palonosetron and Dexamethasone for Prevention of Postoperative Nausea and Vomiting After Middle Ear Surgeries: A Randomized Controlled Study.
BACKGROUND
Postoperative nausea and vomiting (PONV) are one of the common distressing conditions after anesthesia. The PONV are related to several potential risk factors are patient related, anesthesia related, and surgery related. In surgery-related risk, middle ear surgery is associated with a high incidence of PONV.
AIMS
This study aimed to compare the efficiency of palonosetron versus palonosetron with dexamethasone in the prevention of PONV in middle ear surgeries.
SETTINGS AND DESIGN
This was a prospective, randomized, double-blind study.
STATISTICAL ANALYSIS
The data were presented as descriptive statistics for continuous variables and percentages for categorical variables and were subjected to Z-test/Chi-square test/Fisher's exact test. The value of < 0.05 was considered statistically significant.
RESULTS
Demographic parts in comparison to age, duration of surgery, and duration of anesthesia were similar in both the groups. Our study showed that the incidence of PONV during 0-6 h was 38% ( = 19) in Group A and 12% ( = 6) in Group B and the incidence during 6-12 h postoperatively was 14% ( = 7) in Group A and 8% ( = 4) in Group B. During 12-24 h, the incidence was 8% ( = 4) and 6% ( = 3) in Group A and B, respectively. Hence, the difference of total early PONV in Group A was 60% ( = 30) and in Group B, it was 26% ( = 13) which was statistically significant ( < 0.03).
CONCLUSIONS
The above result proves that palonosetron and dexamethasone group is superior in the prevention of PONV in middle ear surgery.
PubMed: 36249139
DOI: 10.4103/aer.aer_131_21 -
Scientific Reports May 2024Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma, for which cyclophosphamide, doxorubicin, vincristine, and prednisone with...
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma, for which cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab(R-CHOP) is one of the standard regimens. Given that R-CHOP is highly emetogenic, chemotherapy-induced nausea and vomiting (CINV) prevention is clinically important. However, there is a paucity of studies focusing on these patients. This study aimed to ascertain the effectiveness of an oral fixed-dose combination of netupitant and palonosetron (NEPA) in preventing CINV in patients with DLBCL undergoing first-line R-CHOP chemotherapy. Seventy patients were enrolled in this single-center prospective non-comparative study conducted between November 2020 and May 2023 in South Korea. NEPA was administered 1 h prior to chemotherapy initiation on day 1. The primary endpoint of the study was the complete response rate (no emesis, and no rescue medication) during the acute, delayed, and overall phases, which were assessed over a period of 120 h post-chemotherapy. The complete response rates for NEPA were 90.0% [95% CI 80.5, 95.9] for the acute phase, 85.7% [95% CI 75.3, 92.9] for the delayed phase, and 84.3% [95% CI 73.6, 91.9] for the overall phase, with no-emesis rates (acute: 97.1% [95% CI 97.1, 99.7], delayed: 95.7% [95% CI 88.0, 99.1], overall: 92.9% [95% CI 84.1, 97.6]). NEPA was well tolerated with no severe treatment-emergent adverse events. NEPA exhibited substantial efficacy in mitigating CINV in DLBCL patients undergoing R-CHOP chemotherapy, demonstrating high CR and no-emesis rates, and favorable safety profiles.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Cyclophosphamide; Male; Female; Middle Aged; Vincristine; Nausea; Vomiting; Rituximab; Prednisone; Aged; Palonosetron; Adult; Prospective Studies; Antiemetics; Pyridines; Treatment Outcome; Drug Combinations; Isoquinolines; Quinuclidines
PubMed: 38755279
DOI: 10.1038/s41598-024-62057-4 -
Cancer Chemotherapy and Pharmacology Jul 2021Chemotherapy-induced nausea and vomiting (CINV) is considered one of the most serious adverse events affecting chemotherapy-receiving cancer patients. It dramatically... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of clinical outcomes and efficacy of palonosetron and granisetron in combination with dexamethasone in Egyptian patients receiving highly emetogenic chemotherapy.
BACKGROUND
Chemotherapy-induced nausea and vomiting (CINV) is considered one of the most serious adverse events affecting chemotherapy-receiving cancer patients. It dramatically affects their food intake, nutritional status and more importantly their quality of life. We can observe CINV in highly emetogenic chemotherapy (HEC) such as adriamycin-cyclophosphamide combination (AC) in breast cancer patients and cisplatin-based regimens in other cancer types. This study aimed to evaluate the antiemetic efficacy of palonosetron (PALO) over granisetron (GRA) in combination with dexamethasone for multiple highly emetogenic chemotherapy drugs (HEC), especially in chemotherapy regimens in Egyptian breast cancer patients and cisplatin-based regimens in other diseases.
PATIENTS AND METHODS
An open-label randomized trial was carried out, including 115 patients receiving at least four cycles of highly emetogenic chemotherapy regimens. All patients received dexamethasone in combination with the 5-HT3 receptor antagonist. We recorded patients' clinical and biochemical characteristics and withdraw blood samples to monitor serum substance P and serotonin in correlation with chemotherapy-induced nausea and vomiting (CINV). We use the MASCC antiemetic tool in the acute phase (0-24 hr) and delayed phase (24-120 h) to evaluate patient outcomes in both stages after each chemotherapy cycle.
RESULTS
In (PALO) group, only 7.84% of patients showed acute vomiting, and 11.76% showed acute nausea, whereas 43.75% of patients showed acute vomiting and 89.06% showed acute nausea in (GRA) group (P < 0.0001). For delayed CINV, 23.53% of patients showed delayed vomiting, and 47.06% showed delayed nausea in the (PALO) group, while 82.81% of patients showed delayed emesis, and 92.19% showed delayed nausea in (GRA) group (P < 0.0001). The study showed that PALO is a cost-effective choice when compared to GRA in CINV prevention as 45.10% of patients in (PALO) required additional rescue medications (Domperidone 10 mg orally three times per day plus Trimebutine 200 mg orally three times per week both for 5 days), while 95.24% in the (GRA) group used the same medications. Adverse events of both antiemetic drugs (PALO and GRA) include headaches and constipation and QTc prolongation reports, mostly mild to moderate, with relatively low rates among the two groups.
CONCLUSION
Palonosetron, combined with dexamethasone, is more effective than granisetron and dexamethasone combination against both acute and delayed emesis induced by highly emetogenic chemotherapy (HEC) cisplatin-based protocols and the combination of cyclophosphamide and anthracyclines (AC). Medical team members should make more efforts, especially clinical pharmacy personnel, to monitor medications' effectiveness and help the medical team achieve a suitable and reliable care plan.
Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Therapy, Combination; Egypt; Female; Granisetron; Humans; Male; Middle Aged; Nausea; Palonosetron; Quality of Life; Vomiting
PubMed: 33835230
DOI: 10.1007/s00280-021-04257-7 -
Core Evidence 2015The second-generation 5-hydroxytryptamine-3 (5-HT3) receptor antagonist palonosetron is effective in the prevention of chemotherapy-induced nausea and vomiting (CINV)... (Review)
Review
INTRODUCTION
The second-generation 5-hydroxytryptamine-3 (5-HT3) receptor antagonist palonosetron is effective in the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with highly and moderately emetogenic chemotherapy (HEC and MEC, respectively). In addition, palonosetron has been the first and, at present, the only 5-HT3 receptor antagonist to have a specific indication for the prevention of delayed CINV associated with MEC. The unique pharmacology of this antagonist is thought to partly explain its improved efficacy against delayed symptoms.
AIMS
To review the evidence underlying the use of palonosetron in preventing CINV.
EVIDENCE REVIEW
A recent meta-analysis consistently showed that palonosetron significantly increases the control of both emesis and nausea during the acute and delayed phases after single-day HEC or MEC. Consistent with these findings from trials that did not include an neurokinin-1 (NK-1) receptor antagonist, randomized controlled trials recently showed that a triple combination with palonosetron achieves significantly better control of delayed CINV, particularly delayed nausea, in patients undergoing HEC or the high-risk combination of an anthracycline and cyclophosphamide (AC). Evidence from randomized studies also supports palonosetron as a valuable option to reduce the total corticosteroid dose administered in patients undergoing multiple cycles of MEC or AC chemotherapy. Additional benefits of palonosetron include the lack of a warning on cardiac safety and no known clinically significant drug-drug interactions. Place in therapy and conclusion: Evidence currently available indicates that palonosetron significantly adds to the clinician's ability to effectively control CINV in patients undergoing HEC or MEC. It is recommended in the international guidelines for the prevention of CINV caused by MEC. The high safety profile and the opportunity to reduce the total corticosteroid dose with no loss in efficacy against delayed CINV should also contribute to a wider use of palonosetron in clinical practice.
PubMed: 26345982
DOI: 10.2147/CE.S65555 -
Biological & Pharmaceutical Bulletin 2021Patients who undergo multiple-day chemotherapy sessions experience hard-to-treat nausea and vomiting. Currently, there is no effective standard treatment for this...
Patients who undergo multiple-day chemotherapy sessions experience hard-to-treat nausea and vomiting. Currently, there is no effective standard treatment for this condition. This study compared the preventive effect of first-generation 5-hydroxytryptamine 3 receptor antagonists (5-HT RAs) and second-generation 5-HT RAs palonosetron in multiple-day chemotherapy-induced nausea and vomiting. The design of this study was a retrospective case-control study of patients who received a five-day cisplatin-based chemotherapy and were treated with aprepitant, dexamethasone, granisetron, and ramosetron or palonosetron. The patients were divided into two groups: patients given granisetron and ramosetron (the first-generation group), and those given palonosetron (palonosetron group). The percentage of patients with a complete response or total control was assessed. They were divided into three phases: 0-216 h (overall phase), 0-120 h (remedial phase), and 120-216 h (after phase). The remedial phase was further divided into 0-24 h (early phase) and 24-120 h (later phase). Moreover, the nutritional status of each patient was assessed by noting the patients' total calorie-intake per day and total parenteral nutrition. First-generation 5-HT RAs and palonosetron were used for treatment in 18 and 28 patients, respectively. The complete response rate and caloric oral intake of the later phase were higher in the palonosetron group than in the first-generation group. We conclude that palonosetron treatment was more effective than first-generation 5-HT RAs in controlling multiple-day chemotherapy-induced nausea and vomiting.
Topics: Adult; Antiemetics; Antineoplastic Agents; Benzimidazoles; Bleomycin; Drug Therapy, Combination; Etoposide; Female; Granisetron; Humans; Male; Middle Aged; Nausea; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Palonosetron; Platinum Compounds; Retrospective Studies; Serotonin 5-HT3 Receptor Antagonists; Testicular Neoplasms; Vomiting
PubMed: 33790099
DOI: 10.1248/bpb.b20-00609 -
Oncology (Williston Park, N.Y.) Aug 2016Chemotherapy-induced nausea and vomiting (CINV) remains an important adverse effect of cancer therapy. The goal of CINV prophylaxis is to reduce the morbidity associated... (Review)
Review
Chemotherapy-induced nausea and vomiting (CINV) remains an important adverse effect of cancer therapy. The goal of CINV prophylaxis is to reduce the morbidity associated with nausea and vomiting, as well as to preserve quality of life, while maintaining the desired chemotherapy regimen. The US Food and Drug Administration has recently approved new therapies for prevention of CINV, including the neurokinin-1 (NK1) receptor antagonist rolapitant and the fixed-dose combination of the second-generation 5-hydroxytryptamine type 3 receptor antagonist palonosetron with the novel NK1 receptor antagonist netupitant. Alternative agents, like the atypical antipsychotic olanzapine, have also expanded the options available for preventing delayed and refractory CINV. Consensus guidelines for prevention of CINV from several organizations are generally consistent with one another and are updated based on expert review of available clinical trial data. This article will address changes in CINV guidelines over the past 5 years and provide updates on recently approved agents and agents that are expected to be approved, based on published phase III trials. It will also explore other factors affecting optimal CINV control, including the role of patient-related risk factors and the role of physician adherence to antiemetic guidelines in reducing the residual risk of CINV.
Topics: Humans; Postoperative Nausea and Vomiting
PubMed: 27539626
DOI: No ID Found -
Future Oncology (London, England) 2015Current guidelines recommend the combination of a neurokinin-1 (NK1) receptor antagonist (RA) and a 5-hydroxytryptamine-3 (5-HT3) RA, together with corticosteroids, in... (Review)
Review
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
PubMed: 25360998
DOI: 10.2217/fon.14.260 -
Therapeutics and Clinical Risk... 2015Nausea and vomiting are major adverse effects of chemotherapy and can greatly impact patients' quality of life. Although chemotherapy-induced nausea and vomiting (CINV)... (Review)
Review
PURPOSE
Nausea and vomiting are major adverse effects of chemotherapy and can greatly impact patients' quality of life. Although chemotherapy-induced nausea and vomiting (CINV) prevalence is high, treatment remains difficult. Palonosetron is a 5-hydroxytryptamine receptor antagonist (5-HT3RA) approved for treatment of CINV. The purpose of this review is to discuss existing and emerging therapeutic options, and examine studies focusing on palonosetron with regards to efficacy, pharmacology, tolerability, safety, and patient-derived outcomes.
METHODS
A literature search was conducted using Ovid MEDLINE and EMBASE to identify relevant studies using palonosetron alone or in combination with other antiemetics. Studies were extracted if they included complete response (CR), complete control (CC), no nausea, no vomiting, and no rescue medications as an endpoint. Studies were also included if safety endpoints were examined.
RESULTS
Palonosetron alone has been shown to improve CR and CC rates for patients receiving low, moderate, or high emetogenic chemotherapy. Rates were further improved with the addition of dexamethasone, a corticosteroid. Furthermore, the addition of neurokinin-1 receptor antagonists, such as netupitant markedly improved efficacy profiles compared to palonosetron alone. Aprepitant is an antiemetic that has exhibited positive results in combination with palonosetron. Recently, a new drug consisting of netupitant and palonosetron (NEPA) has demonstrated significantly more efficacious prevention of CINV. Regardless of the combination, palonosetron has been well tolerated. The most common adverse events were constipation, headache, fatigue, and dizziness, with the majority of patients describing them as only mild or moderate.
CONCLUSION
Palonosetron, alone or with other antiemetics, has improved CINV treatment due to its ability to significantly reduce delayed phases of CINV, compared to similar 5-HT3RAs. Palonosetron is both more effective than first generation 5-HT3RAs and safer, as it results in a smaller prolongation of the QTc interval, compared to other 5-HT3RAs.
PubMed: 25999723
DOI: 10.2147/TCRM.S68130 -
Minerva Anestesiologica Jun 2023Genetic variants may affect drug efficacy on postoperative nausea and vomiting (PONV). The understanding of these mechanisms will help to identify the surgical patients... (Review)
Review
INTRODUCTION
Genetic variants may affect drug efficacy on postoperative nausea and vomiting (PONV). The understanding of these mechanisms will help to identify the surgical patients who might benefit from specific prophylactic and therapeutic antiemetic treatment. The aim of the present review was to investigate gene polymorphisms that influence 5-hydroxytryptamine (serotonin) type 3 receptor antagonists (5HT3RA) efficacy in PONV.
EVIDENCE AQUISITION
We included articles published from 2005 to 2022, utilizing the electronic databases PUBMED, EMBASE, COHRANE Library and ScienceDirect. To explore the relationship between genetic variations and 5HT3 receptor antagonist efficacy in PONV we focused on three different gene polymorphisms: the cytochrome P450 mono-oxygenase system gene (CYP2D6), the adenosine triphosphate (ATP)-binding cassette subfamily B gene (ABCB1) as well as the 5HT3 receptor gene (5HT3R). We also explored the relationship between the above genetic variations and their impact on 5HT3RA efficacy in the context of chemotherapy induced nausea and vomiting.
EVIDENCE SYNTHESIS
Our search retrieved a total of 70 articles; 29 of them were included in the present review. Regarding polymorphisms of the CYP2D6 gene and the efficacy of serotonin antagonists in PONV, the ultra-rapid metabolizer genotype was associated with reduced efficacy of ondansetron, dolasetron and tropisetron, with the latter presenting more pronounced failure in these patients, while granisetron's efficacy remained unaffected. Regarding variations in the ABCB1 gene, three polymorphisms ("2677G>T/A" in exon 21; "3435C>T" in exon 27; "C1236T" in exon 12) were associated with a better response to ondansetron and ramosetron, while they did not affect palonosetron's efficacy. Additionally, polymporphisms of the 5-HT3B receptor gene were associated with ondancetron's postoperative efficacy; the "100_-102AAG" deletion variant was associated with reduced efficacy, while the Y129S variant did not show any effect on the drug's antiemetic effect.
CONCLUSIONS
This review highlights that inefficacy of a specific drug in managing PONV could be attributed to specific genetic profiles and patients would possibly benefit from a drug switch.
Topics: Humans; Postoperative Nausea and Vomiting; Ondansetron; Pharmacogenetics; Cytochrome P-450 CYP2D6; Antiemetics
PubMed: 36852569
DOI: 10.23736/S0375-9393.22.16983-X