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Medicine Jul 2021Postoperative nausea and vomiting (PONV) is a common complaint in patients following general anesthesia. Various antiemetics, including 5-hydroxytryptamine type 3... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of efficacy between palonosetron-midazolam combination and palonosetron alone for prevention of postoperative nausea and vomiting in patients undergoing breast surgery and patient controlled analgesia: A prospective, randomized, double-blind study: A CONSORT-compliant study.
BACKGROUND
Postoperative nausea and vomiting (PONV) is a common complaint in patients following general anesthesia. Various antiemetics, including 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, are effective but still have limited efficacy. Therefore, combination therapy is preferable to using a single drug alone in high-risk patients. We performed a comparative study on the antiemetic effect of palonosetron, a 5-HT3 receptor antagonist, monotherapy vs palonosetron-midazolam combination therapy for the prevention of PONV.
METHODS
A total of 104 female patients scheduled for breast cancer surgery were enrolled. They were randomly divided into 2 groups, a palonosetron monotherapy group (group P) and palonosetron-midazolam combination therapy group (group PM). Both groups received 0.075 mg palonosetron intravenously after induction of anesthesia. Patient-controlled analgesia (PCA) was applied according to the allocated group. Intravenous (IV)-PCA in group P consisted of fentanyl 20 μg/kg plus normal saline (total volume: 100 ml); IV-PCA in group PM consisted of fentanyl 20 μg/kg plus midazolam 4 mg plus normal saline (total volume: 100 ml). Efficacy parameters were collected during 0 to 1, 1 to 6, 6 to 24, and 24 to 48 hours postoperative time intervals. These measures included complete response (defined as no PONV and no rescue anti-emetic use) rate, incidence of PONV, sedation score, rescue antiemetic use, rescue analgesic use, and numerical rating scale (NRS) for pain. The complete response rate during the 0 to 24 hours interval was analyzed as the primary outcome.
RESULTS
Although the complete response rate between 0 and 24 hours was higher in group PM (42.3% and 48.1% in group P and PM, respectively), there was no statistically significant difference (P = .55). The complete response rates in other time intervals were not different between the 2 groups as well. The sedation score and NRS score also showed no differences between the 2 groups.
CONCLUSIONS
The combination therapy of palonosetron with midazolam did not lead to a greater reduction in the incidence of PONV than monotherapy in patients undergoing breast surgery and receiving IV-PCA containing fentanyl.
Topics: Analgesia, Patient-Controlled; Anesthetics, Intravenous; Antiemetics; Breast Neoplasms; Double-Blind Method; Drug Therapy, Combination; Female; Fentanyl; Humans; Mastectomy; Midazolam; Middle Aged; Palonosetron; Postoperative Nausea and Vomiting; Treatment Outcome
PubMed: 34190167
DOI: 10.1097/MD.0000000000026438 -
National Journal of Maxillofacial... 2022The objective is to evaluate the efficacy of prophylactic single intravenous dose of palonosetron in the management of postoperative nausea and vomiting (PONV) following...
OBJECTIVE
The objective is to evaluate the efficacy of prophylactic single intravenous dose of palonosetron in the management of postoperative nausea and vomiting (PONV) following oral and maxillofacial surgical interventions performed through an intraoral approach under general anesthesia (GA).
MATERIALS AND METHODS
A prospective study was conducted on 100 subjects who underwent intraoral surgical procedures for the management of maxillofacial trauma, pathology, dentofacial anomalies, and deformities under GA. All subjects received a prophylactic single intravenous dose of 0.075 mg palonosetron along with premedication. Predisposing factors for PONV such as patient age, gender, Apfel risk score, history of motion sickness, smoking, type of procedure, and administration of postoperative opioids were taken into consideration. All the patients were monitored for PONV for the 1 24 h postoperatively (PO). First, at an interval of 30 min for 1 4 h and then at every 2 h interval for next 8 h followed by monitoring every 6 h interval till 24 h. Time and frequency of rescue medication were noted.
RESULTS
Seventy-nine percentage subjects did not have PONV. 15% subjects had a single episode of vomiting PO which could be attributed to multiple intra oral surgical sites performed as well as longer duration of exposure to anesthetic agents in addition to providing opioid analgesics for the management of postoperative pain. Only 6% subjects needed rescue antiemetic drug. Palonosetron did not show any significant changes in cardiac status and serum profile.
CONCLUSION
Palonosetron is effective in the management of PONV for maxillofacial surgical procedures performed through an intraoral approach under GA.
PubMed: 36051795
DOI: 10.4103/njms.NJMS_346_21 -
European Review For Medical and... Aug 2021The outbreak of coronavirus disease 2019 (COVID-19) has affected the treatment of cancer patients, with particular regard to the management of both chemotherapy and side...
NEPA (netupitant/palonosetron) for the antiemetic prophylaxis of nausea and vomiting induced by chemotherapy (CINV) with Folfirinox and Folfoxiri even during the COVID-19 pandemic: a real-life study.
OBJECTIVE
The outbreak of coronavirus disease 2019 (COVID-19) has affected the treatment of cancer patients, with particular regard to the management of both chemotherapy and side effects. Chemotherapy-induced nausea and vomiting (CINV) are amongst the most troublesome side effects that impair patients' adherence to treatments and their quality of life (QoL). NEPA (Akynzeo®), is an oral fixed-dose combination of netupitant [a neurokinin-1 receptor antagonist (NK1RA), 300 mg] and palonosetron [(5-hydroxytryptamine (serotonin or 5HT) type3 receptor antagonist (5HT3RA), 0.5 mg] which has been shown to be effective in preventing CINV.
PATIENTS AND METHODS
This prospective study started before the outbreak of COVID-19 and was carried out during the pandemic period. The aim was to evaluate the efficacy and safety of a single oral dose NEPA plus 12 mg of dexamethasone (DEX) in patients treated with Folfoxiri plus Bevacizumab and Folfirinox. The patients were diagnosed with advanced colorectal cancer (CRC) or advanced pancreatic ductal adenocarcinoma (PDAC). They were divided into two groups: naïve patients and patients previously treated with serotonin receptor antagonists (5HT3-RA) and neurokin-1 receptor antagonists (NK1-RA).
RESULTS
During the overall phase, the complete response (CR) rate was 96.8% in naïve patients treated with Folfoxiri plus Bevacizumab, and 94.6% in patients treated with Folfirinox. During the acute and delayed phases, the CR rate was 92.8% and 94.2%, with Folfoxiri and Bevacizumab, as well as 96.2% and 94.6%, with Folfirinox. There was no adequate control of CINV events in patients on antiemetic prophylaxis with 5HT3-RA or NK1-RA associated with cortisone. During the overall phase, the CR rate was 74.6% with Folfoxiri plus Bevacizumab and 75.8% with Folfirinox. During the acute and delayed phases, the CR rate was 72.5% and 74.8% with Folfoxiri plus Bevacizumab, as well as 75.2% and 74.6% with Folfirinox.
CONCLUSIONS
This study has shown the therapeutic benefits of NEPA in the management and prophylaxis of CINV events, both in naive patients and patients previously treated with 5HT3-RA and NK1-RA. In addition, NEPA has been shown to be safe, both before and during the COVID-19 pandemic.
Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; COVID-19; Colorectal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Nausea; Oxaliplatin; Palonosetron; Pandemics; Prospective Studies; Pyridines; Vomiting
PubMed: 34486707
DOI: 10.26355/eurrev_202108_26552 -
Supportive Care in Cancer : Official... Sep 2019Radiation-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... (Review)
Review
PURPOSE
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.
METHODS
A selective review of research conducted in a palliative outpatient radiotherapy clinic relating to antiemetic management for RINV was performed.
RESULTS
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.
CONCLUSIONS
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
PubMed: 31119459
DOI: 10.1007/s00520-019-04870-6 -
Cancer Medicine May 2020To investigate whether palonosetron is better than granisetron in preventing chemotherapy-induced nausea and vomiting (CINV) in a three-drug combination with... (Comparative Study)
Comparative Study Randomized Controlled Trial
A double-blind, randomized, multicenter phase 3 study of palonosetron vs granisetron combined with dexamethasone and fosaprepitant to prevent chemotherapy-induced nausea and vomiting in patients with breast cancer receiving anthracycline and cyclophosphamide.
PURPOSE
To investigate whether palonosetron is better than granisetron in preventing chemotherapy-induced nausea and vomiting (CINV) in a three-drug combination with dexamethasone and fosaprepitant (Fos) in patients with breast cancer who are placed on anthracycline and cyclophosphamide (AC-based regimen).
PATIENTS AND METHODS
Chemo-naive women with primary breast cancer were randomly administered either palonosetron 0.75 mg (day 1) or granisetron 1 mg (day 1) combined with dexamethasone (12 mg at day 1, 8 mg at day 2 and day 3) and Fos 150 mg (day 1) before receiving AC-based regimen in a double-blind study. The primary endpoint was the complete response (CR) rate of emesis in cycle 1 in the delayed phase. This was defined as neither vomiting nor rescue drug usage for emesis at >24-120 hours after chemotherapy. Secondary endpoints were the CR in the acute/overall phase (0-24/0-120 hours, respectively, after chemotherapy), no nausea and vomiting, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and safety.
RESULTS
From December 2012 to October 2014, 326 patients were treated and evaluated (164/162 evaluable patients in granisetron/palonosetron arm, respectively). The CR during the delayed phase was 60.4% in the granisetron regimen and 62.3% in the palonosetron regimen. The CR during acute phase (73.2% vs 75.9%, respectively) and the CR during overall phase (54.9% in both regimens) were very identical. A significantly higher number of patients in the palonosetron arm were free from nausea during the delayed phase (28% vs 40.1%; P = .029). Adverse events were also identical, although infusion site reactions (ISR) were higher (20.3%-23.3%) than preceding studies in both regimens.
CONCLUSION
In combination with dexamethasone and Fos, this study suggests that palonosetron is not better than granisetron in chemo-naive patients with primary breast cancer receiving AC-based regimen. Administration of Fos in peripheral veins after AC-based regimen increased ISR.
Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Double-Blind Method; Doxorubicin; Drug Therapy, Combination; Epirubicin; Female; Fluorouracil; Granisetron; Humans; Middle Aged; Morpholines; Nausea; Palonosetron; Patient Reported Outcome Measures; Vomiting
PubMed: 32168551
DOI: 10.1002/cam4.2979 -
Advances in Therapy May 2023Chemotherapy-induced nausea and vomiting (CINV) is often ranked by patients as one of the most distressing and feared consequences of chemotherapy. The novel... (Review)
Review
Chemotherapy-induced nausea and vomiting (CINV) is often ranked by patients as one of the most distressing and feared consequences of chemotherapy. The novel neurokinin-1 (NK) receptor antagonist fosnetupitant, a phosphorylated prodrug formulation of netupitant, was approved in Japan in 2022. Fosnetupitant is one of the standard treatments for the prevention of CINV in patients who are receiving highly (any treatment where CINV occurs in more than 90% of patients) or moderately (where CINV occurs in 30-90% of patients) emetogenic chemotherapies. The aim of this commentary is to describe the mechanism of action, tolerability, and antiemetic efficacy of single-agent fosnetupitant in the prevention of CINV, and to discuss its clinical application, in order to aid optimal use.
Topics: Humans; Vomiting; Nausea; Antiemetics; Quinuclidines; Antineoplastic Agents
PubMed: 36884027
DOI: 10.1007/s12325-023-02474-5 -
Journal of Geriatric Oncology Jul 2023We recently demonstrated the non-inferiority of two dexamethasone (DEX)-sparing regimens with an oral fixed-combination of netupitant and palonosetron (NEPA) versus the... (Randomized Controlled Trial)
Randomized Controlled Trial
Dexamethasone-sparing regimens with NEPA (netupitant/palonosetron) for the prevention of chemotherapy-induced nausea and vomiting in older patients (>65 years) fit for cisplatin: A sub-analysis from a phase 3 study.
INTRODUCTION
We recently demonstrated the non-inferiority of two dexamethasone (DEX)-sparing regimens with an oral fixed-combination of netupitant and palonosetron (NEPA) versus the guideline-recommended DEX use for cisplatin-induced nausea and vomiting. Since prevention of chemotherapy-induced nausea and vomiting is critical in older patients, we retrospectively evaluated the efficacy of the DEX-sparing regimens in this subset.
MATERIALS AND METHODS
Chemo-naive patients aged >65 years treated with high-dose cisplatin (≥70 mg/m) were eligible. Patients received NEPA and DEX on day 1 and were randomized to receive either (1) no further DEX (DEX1), (2) oral low-dose DEX (4 mg) on days 2-3 (DEX3), or (3) the guideline-recommended standard DEX (4 mg twice daily) on days 2-4 (DEX4). The primary efficacy endpoint of the parent study was complete response (CR; no vomiting and no use of rescue medication) during the overall phase (days 1-5). No significant nausea (NSN; none or mild nausea) and the proportion of patients reporting no impact on daily life (NIDL) which was evaluated by the Functional Living Index-Emesis questionnaire on day 6 (overall combined score > 108), were secondary endpoints.
RESULTS
Among the 228 patients in the parent study, 107 were > 65 years. Similar CR rates [95% confidence intervals (CI)] were observed in patients over 65 years across treatment groups [DEX1: 75% (59.7-86.8%); DEX3: 80.6% (62.5-92.6%); DEX4: 75% (56.6-88.5%)] as well as versus the total study population. NSN rates were also similar in the older-patients across treatment groups (p = 0.480) but were higher compared with the total population. Similar rates of NIDL (95% CI) were reported in the older-patient subset across treatment groups [DEX1: 61.5% (44.6-76.6%); DEX3: 64.3% (44.1-81.4%); DEX4: 62.1% (42.3-79.3%); p = 1.0] during the overall phase, as well as versus total population. A similar proportion of older patients across treatment groups experienced DEX-related side effects.
DISCUSSION
This analysis shows that older-patients who are fit for cisplatin benefit from a simplified regimen of NEPA plus single-dose DEX with neither loss in antiemetic efficacy nor the adverse impact on patient daily functioning. The study was registered on ClinicalTrials.gov (identifier NCT04201769) on 17/12/2019 (retrospectively registered).
Topics: Humans; Aged; Cisplatin; Palonosetron; Retrospective Studies; Nausea; Antiemetics; Dexamethasone; Drug-Related Side Effects and Adverse Reactions; Antineoplastic Agents
PubMed: 37290207
DOI: 10.1016/j.jgo.2023.101537 -
Current Medical Research and Opinion Apr 2022Cost-effectiveness analyses that consider all currently used antiemetics in the case of emetogenic chemotherapy-induced nausea and vomiting (CINV) have not been...
OBJECTIVE
Cost-effectiveness analyses that consider all currently used antiemetics in the case of emetogenic chemotherapy-induced nausea and vomiting (CINV) have not been performed yet. We aim to compare the cost-effectiveness of olanzapine (OLA), or/and neurokinin-1 receptor antagonists (NK-1-RAs), in combination with palonosetron (PAL) and dexamethasone (DEX) in preventing highly emetogenic CINV.
METHODS
Two decision analytic models were constructed. The first model was based on overall complete response (CR); the second model was based on rate of absence of nausea. Four antiemetic regimens PAL + DEX, NK-1-RAs + PAL + DEX, OLA + PAL + DEX, and PAL + NK-1-RA + DEX + OLA were compared in terms of cost, overall CR and rate of absence of nausea. Base case incremental cost-effectiveness ratio (ICER) estimates were calculated. The study was from the US payer perspective.
RESULTS
In terms of CR, the PAL + NK-1-RA + DEX + OLA was associated with the highest gains in the percentage of CR among all treatment regimens at base case ICERs of $4220 versus PAL + DEX, $4656 versus NK-1-RA + PAL + DEX, $16,471 versus OLA + PAL + DEX. In term of rate of absence of nausea, the PAL + NK-1-RA + DEX + OLA was associated with the highest rate of absence of nausea among all the treatment regimens at base case ICERs of $2291 versus PAL + DEX, $1304 versus NK-1-RA + PAL + DEX, $2657 versus OLA + PAL + DEX.
CONCLUSION
from an economic perspective, our study revealed that whether to use overall CR or/and rate of absence of nausea as determinants in the antiemetic decision for the CINV patients, the CR-based-, and rate of absence of nausea-based cost-effectiveness analyses, showed negotiable ICER estimates for the treatment PAL + NK-1-RA + DEX + OLA over the combinations PAL + DEX, NK-1-RA + PAL + DEX, and OLA + PAL + DEX regimens.
Topics: Antiemetics; Antineoplastic Agents; Cost-Benefit Analysis; Dexamethasone; Humans; Nausea; Palonosetron; Quinuclidines; Vomiting
PubMed: 35068277
DOI: 10.1080/03007995.2022.2033011 -
Biological & Pharmaceutical Bulletin 2024Although carboplatin (CBDCA) is classified as a moderately emetogenic agent, the majority of guidelines recommend the use of a neurokinin-1 receptor antagonist in...
Although carboplatin (CBDCA) is classified as a moderately emetogenic agent, the majority of guidelines recommend the use of a neurokinin-1 receptor antagonist in addition to a 5-hydroxytryptamine type 3 receptor antagonist with dexamethasone (DEX) for CBDCA-containing chemotherapy because of its higher emetogenic risk. However, the additional efficacy of aprepitant (APR) in CBDCA-containing treatment remains controversial, and data on multiple-day treatments are limited. Etoposide (ETP) was administered on days 1-3 in the CBDCA + ETP regimen, and it is important to evaluate suitable antiemetic therapy for the regimen. Therefore, we evaluated the efficacy of additional APR in CBDCA + ETP. Patients were divided into two groups and retrospectively evaluated. One was the control group, which was prophylactically administered palonosetron (PALO) and DEX, and the other was the APR group, which received APR orally with PALO and DEX. The primary endpoint was complete response (CR) between the groups. The overall CR rates were 75.0 and 76.4% in the control and APR groups, respectively, with no significant difference (p = 1.00). In the acute phase, it was 88.9 and 97.2%, respectively, and 86.1 and 79.2% in the delayed phase, respectively, without significant differences (p = 0.10 and 0.38, respectively). The incidence and severity of nausea, vomiting, and anorexia were not significantly different between the two groups in the acute and delayed phases. Our findings suggest that combining APR with PALO and DEX does not improve the CR rate in CBDCA + ETP therapy.
Topics: Aprepitant; Carboplatin; Humans; Dexamethasone; Palonosetron; Male; Etoposide; Antiemetics; Female; Middle Aged; Vomiting; Aged; Nausea; Retrospective Studies; Adult; Drug Therapy, Combination; Antineoplastic Combined Chemotherapy Protocols; Quinuclidines; Morpholines; Antineoplastic Agents; Isoquinolines; Treatment Outcome
PubMed: 38897969
DOI: 10.1248/bpb.b24-00046 -
Japanese Journal of Clinical Oncology Aug 2021Palonosetron has demonstrated non-inferiority to ondansetron for prevention of chemotherapy-induced nausea and vomiting in pediatric patients in the United States and...
BACKGROUND
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.
METHODS
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%.
RESULTS
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.
CONCLUSION
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.
TRIAL REGISTRATION
JapicCTI-163305, registered 6 June 2016.
Topics: Antiemetics; Antineoplastic Agents; Child; Dexamethasone; Double-Blind Method; Humans; Infant, Newborn; Isoquinolines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Vomiting
PubMed: 34021341
DOI: 10.1093/jjco/hyab079