Palonosetron for prevention of delayed chemotherapy-induced nausea and vomiting in pediatric patients: a meta-analysis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) are common adverse events in patients undergoing emetogenic chemotherapy. Palonosetron, a second-generation 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA), has demonstrated non-inferiority to first-generation 5-HT3 RAs for CINV in pediatric patients. Although palonosetron has a long half-life and prolonged antiemetic action, its efficacy against delayed CINV in pediatric patients is not well understood. Therefore, this meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy of palonosetron for delayed CINV in pediatric patients. METHODS: A literature search of MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science databases was performed. A meta-analysis was performed using forest plots, and risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. A funnel plot was constructed to explore publication bias. RESULTS: The literature search retrieved 842 records, of which 23 full-text articles were assessed, including six RCTs. Meta-analysis of four RCTs that reported on the complete response (CR: defined as no emesis and no rescue medication) rate for delayed CINV revealed that palonosetron was statistically superior to first-generation 5-HT3 RAs (RR = 1.21 [95% CI 1.09-1.35]; p < 0.01). Although the number of studies included was small, no publication bias was observed in the funnel plots. In addition, the CR rate for overall and acute CINV was also significantly higher for palonosetron (RR = 1.25 [95% CI 1.01-1.54]; p = 0.04 and RR = 1.06 [95% CI 1.01-1.12]; p = 0.03, respectively). CONCLUSION: Palonosetron is effective in the prophylaxis of delayed CINV in pediatric patients.

Efficacy of the dexamethasone-sparing triplet regimen for preventing cisplatin-induced emesis: a combined analysis.

Aim: To further evaluate the antiemetic efficacy of single-dose versus multiple-dose dexamethasone (DEX) against nausea and vomiting caused by cisplatin. Materials & methods: Two similar non-inferiority studies were pooled. Patients were randomized to single-day DEX or multiple-day DEX plus palonosetron and neurokinin-1 receptor-antagonists (NK-1RAs). The primary endpoint was complete response (CR; no vomiting and no rescue medication) during the overall phase. Results: The combined analysis included 242 patients. The absolute risk difference between single day versus multi-day DEX for CR was -2% (95% CI, -14 to 9%). Conclusion: Administration of single-dose DEX offers comparable antiemetic control to multiple-day DEX when combined with palonosetron and an NK-1RA in the setting of single-day cisplatin.

We aimed at further evaluating how well the corticosteroid, dexamethasone (DEX), works as measured in two similar clinical studies of single-day versus multiple-day DEX for the prevention of nausea and vomiting caused by cisplatin, a cell-killing drug, which has high potential of triggering nausea and vomiting. In both studies, cancer patients were randomly assigned to 1-day DEX or multiple-day DEX (3­4 days) in combination with palonosetron (this antagonist attaches to a specific receptor for serotonin without triggering nausea and vomiting), and neurokinin-1 receptor-antagonists (NK-1RAs; they attach to the NK-1 receptor without triggering nausea and vomiting). The combined analysis of the two studies, which includes 242 patients, showed that a single dose of DEX is as effective as multiple-day DEX in terms of the number of patients achieving complete response (defined as no vomiting and no 'as-needed' use of antiemetics) during the 5 days after cisplatin administration. Therefore, administration of single-dose DEX offers comparable antiemetic control to multiple-day DEX when combined with palonosetron and an NK-1RA in patients undergoing single-day cisplatin.

Multicenter, placebo-controlled, double-blind, randomized study of fosnetupitant in combination with palonosetron for the prevention of chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy.

BACKGROUND: The current randomized, double-blind, phase 2 study assessed the efficacy and safety profile of a single intravenous administration of fosnetupitant, a neurokinin 1 receptor antagonist prodrug, for the prevention of chemotherapy-induced nausea and vomiting in Japanese patients receiving cisplatin-based chemotherapy. METHODS: Patients scheduled to receive cisplatin (at a dose of ≥70 mg/m2 )-based regimens were randomly assigned to receive fosnetupitant at a dose of 81 mg or 235 mg or placebo in combination with palonosetron at a dose of 0.75 mg and dexamethasone. The primary endpoint was complete response (CR; no vomiting and no rescue medication) during the overall phase (0-120 hours). The overall CR rate was compared between each dose of fosnetupitant and the placebo group adjusting for the stratification factors of sex and age class (age <55 years vs age ≥55 years). Safety was assessed, with special attention given to events that potentially were suggestive of infusion site reactions. RESULTS: A total of 594 patients were randomized. Of these, 194 patients, 195 patients, and 195 patients, respectively, in the placebo and fosnetupitant 81-mg and 235-mg dose groups were evaluable for efficacy. The overall CR rate was 54.7% for the placebo group, 63.8% for the fosnetupitant 81-mg dose group (adjusted difference, 9.1%; 95% CI, -0.4% to 18.6% [P = .061]), and 76.8% for the fosnetupitant 235-mg dose group (adjusted difference, 22.0%; 97.5% CI, 11.7% to 32.3% [P < .001]). Safety profiles were comparable between the 3 groups. The incidence of infusion site reactions related to fosnetupitant was ≤1% in each dose group. CONCLUSIONS: Fosnetupitant at a dose of 235 mg provided superior prevention of chemotherapy-induced nausea and vomiting among patients receiving cisplatin-based chemotherapy compared with the control group, and with a satisfactory safety profile.

Guideline for the prevention of acute chemotherapy-induced nausea and vomiting in pediatric cancer patients: A focused update.

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-HT3 antagonists recommended for children receiving highly emetogenic chemotherapy (HEC) and the recommendation of aprepitant for children 6 months of age or older receiving HEC. To optimize CINV control in children, future work must focus on closing critical research gaps.

Palonosetron compared with ondansetron in pediatric cancer patients: multicycle analysis of a randomized Phase III study.

AIM: 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 & METHODS: Patients were randomly assigned to 10, 20 µg/kg palonosetron or 3 × 150 µg/kg ondansetron for up to four cycles of HEC/MEC. RESULTS: 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. CONCLUSION: 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.

Role of olanzapine in chemotherapy-induced nausea and vomiting on platinum-based chemotherapy patients: a randomized controlled study.

PURPOSE: Even with the use of modern antiemetic drugs, chemotherapy-induced nausea and vomiting (CINV) is still a cause of great distress to the patients. Olanzapine, primarily marketed as an antipsychotic, was found to reduce nausea and vomiting in some chemotherapy patients. But it was never tested in Indian population with a diverse genetic background. The present study aims to evaluate the role of olanzapine in CINV in patients receiving platinum-based chemotherapy. METHODS: The study was a randomized, controlled, assessor-blinded study on 100 chemotherapy-naïve consenting patients receiving any one from cisplatin, carboplatin or oxaliplatin. The control group (n = 50) received palonosetron and dexamethasone in the approved therapeutic dose from the day 1 of chemotherapy. The test group (n = 50) received additional olanzapine 10 mg/day from day 1 for five consecutive days. CINV and quality of life (QoL) were assessed. RESULTS: Vomiting was significantly less among the olanzapine-treated patients. Control of delayed emesis was significantly better in this group (complete response among 96 vs. 42 % in the control group, p value <0.0001). Incidence and severity of nausea was significantly less in this group. Failure of anti-CINV measure was 4 % in this group compared to 26 % of the patients of the control group during overall days 1-5. Though sedation was more in these olanzapine-treated patients, there was no dose-limiting adverse event. Quality of life was also better among the olanzapine-treated patients. CONCLUSION: Olanzapine was found to be effective as add-on in the control of CINV.

Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.

BACKGROUND: Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. STUDY DESIGN: Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. SETTING & PARTICIPANTS: Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa. INTERVENTION: Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited. OUTCOMES: Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). MEASUREMENTS: Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). RESULTS: Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (P<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed with epoetin alfa. No safety concerns were raised. LIMITATIONS: Short treatment duration and small sample size. CONCLUSIONS: In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels.

Randomized phase III trial of APF530 versus palonosetron in the prevention of chemotherapy-induced nausea and vomiting in a subset of patients with breast cancer receiving moderately or highly emetogenic chemotherapy.

BACKGROUND: APF530 provides controlled, sustained-release granisetron for preventing acute (0-24 h) and delayed (24-120 h) chemotherapy-induced nausea and vomiting (CINV). In a phase III trial, APF530 was noninferior to palonosetron in preventing acute CINV following single-dose moderately (MEC) or highly emetogenic chemotherapy (HEC) and delayed CINV in MEC (MEC and HEC defined by Hesketh criteria). This exploratory subanalysis was conducted in the breast cancer subpopulation. METHODS: Patients were randomized to subcutaneous APF530 250 or 500 mg (granisetron 5 or 10 mg) or intravenous palonosetron 0.25 mg during cycle 1. Palonosetron patients were randomized to APF530 for cycles 2 to 4. The primary efficacy end point was complete response (CR, no emesis or rescue medication) in cycle 1. RESULTS: Among breast cancer patients (n = 423 MEC, n = 185 HEC), > 70 % received anthracycline-containing regimens in each emetogenicity subgroup. There were no significant between-group differences in CRs in cycle 1 for acute (APF530 250 mg: MEC 71 %, HEC 77 %; 500 mg: MEC 73 %, HEC 73 %; palonosetron: MEC 68 %, HEC 66 %) and delayed (APF530 250 mg: MEC 46 %, HEC 58 %; 500 mg: MEC 48 %, HEC 63 %; palonosetron: MEC 52 %, HEC 52 %) CINV. There were no significant differences in within-cycle CRs between APF530 doses for acute and delayed CINV in MEC or HEC in cycles 2 to 4; CRs trended higher in later cycles, with no notable differences in adverse events between breast cancer and overall populations. CONCLUSIONS: APF530 effectively prevented acute and delayed CINV over 4 chemotherapy cycles in breast cancer patients receiving MEC or HEC. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00343460 (June 22, 2006).

Prolonged drug-induced myoclonus: is it related to palonosetron?

We report a case of drug-induced myoclonus possibly related to palonosetron, a second-generation 5-hydroxytryptamine-3 receptor antagonist which was administered as a prophylaxis for postoperative nausea and vomiting in a 28-year-old female. The recurrent episodes of myoclonus jerk involving the head, neck and shoulder persisted for a period of 4 days. The patient also exhibited an episode of severe bradycardia leading to hypotension 7 h after surgery. To our knowledge, this is the first report presenting these adverse events potentially associated with the use of palonosetron.

Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron.

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.

Palonosetron in combination with 1-day versus 3-day dexamethasone to prevent nausea and vomiting in patients receiving paclitaxel and carboplatin.

PURPOSE: The aim of the present study was to evaluate the efficacy and toxicity of palonosetron (PAL) and dexamethasone (DEX) on day 1 only in patients with gynecologic cancer receiving paclitaxel combined with carboplatin (TC). The primary endpoint was to evaluate the complete response (CR) rate in the delayed phase. METHODS: This study was a randomized phase 2. Regardless of assignment to either study arm, all patients received an intravenous prophylactic regimen of DEX (20 mg) within 15 min and then an intravenous dose of PAL (0.75 mg) as a bolus given 30 min before initiation of TC on day 1. Patients in the DEX 1-day group received no additional DEX on days 2 and 3. Patients in the DEX 3-day group received DEX (8 mg) orally on days 2 and 3. RESULTS: Eighty-two patients had evaluable data on the primary outcome. The CR rates in the delayed phase between the two groups were not statistically significantly different (3-day group, 76.9 % [30/39]; 1-day group 69.8 % [30/43]; p = 0.4652). The frequency of constipation and insomnia which were antiemetic treatment-related adverse events was similar between two groups, and no serious adverse events occurred. CONCLUSIONS: Administration of a combination of PAL and DEX 1 day may prevent chemotherapy-induced nausea and vomiting (CINV) in the delayed phase for TC as well as administration of DEX 3 days. Further evaluation of the antiemetic regimen of combination of PAL and DEX 1 day for TC is warranted in future phase 3 trials.

New and emerging therapeutic options for the management of chemotherapy-induced nausea and vomiting.

Chemotherapy-induced nausea and vomiting (CINV) remains one of the most challenging adverse events of chemotherapy, and one that has substantial negative effects on patients, clinicians, and the wider health care system. Use of CINV prophylaxis consistent with clinical practice guidelines is essential for attaining optimal CINV control. In recent years, there has been a dramatic improvement in the control of CINV with the introduction of effective antiemetic agents, including the serotonin (5-hydroxytryptamine [5-HT3]) receptor antagonists (ondansetron, granisetron, and palonosetron) and the neurokinin-1 (NK1) receptor antagonists (aprepitant and fosaprepitant). An important benefit of the newer antiemetic agents is their improved ability to control the delayed CINV that can develop in the days after chemotherapy administration. In October 2014, a fixed-dose oral combination containing the novel NK1 receptor antagonist netupitant and palonosetron (NEPA) received approval from the US Food and Drug Administration. The combination of 2 effective antiemetic agents in a single, oral capsule may help simplify CINV management. Ongoing studies are evaluating new CINV approaches (eg, the novel NK1 receptor antagonist rolapitant), as well as the optimal use of existing therapies. Patient education regarding the timing, prevention, and treatment of CINV is another key component of CINV management.

Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following paclitaxel and carboplatin in patients with gynecologic cancers: A randomized, multicenter, phase-II trial.

AIM: Chemotherapy-induced nausea and vomiting (CINV) can affect a patient's quality of life, leading to poor compliance with further treatments. Previous studies have provided minimal data about carboplatin-based regimens. Female sex is a known risk factor for CINV. The purpose of this study was to evaluate palonosetron plus single-dose dexamethasone (DEX) for preventing CINV caused by carboplatin plus paclitaxel combination therapy (TC regimen) in patients with gynecologic cancers. MATERIAL AND METHODS: Patients were recruited for this phase-II, multicenter, randomized trial from 12 hospitals in Hokkaido, Japan. Eligible patients were women with uterine cervical, endometrial or ovarian cancer scheduled to receive conventional TC regimen or dose-dense TC regimen; 116 patients were randomly assigned to receive palonosetron in combination with 1-day DEX or 3-day DEX. RESULTS: During the overall period, complete response (CR) was observed in 67.9% (95% confidence interval, 53.7-80.1) of patients in the 3-day DEX arm, and 60.7% (95% confidence interval, 46.8-73.5) of patients in the 1-day DEX arm; CR was significantly lower in the 1-day DEX arm if motion sickness was already present (P = 0.0370). In the severe hyperemesis gravidarum cohort, CR in the 1-day DEX arm tended to be lower than in the 3-day DEX arm. CONCLUSION: Combination therapy of palonosetron and 1-day DEX was effective for subjects undergoing a TC regimen for gynecologic cancers. However, the possibility of reduced efficacy of 1-day only DEX therapy in women undergoing a TC regimen could not be refuted and requires further investigation.

A Meta-Analysis of Palonosetron for the Prevention of Postoperative Nausea and Vomiting in Adults.

PURPOSE: The aim of this meta-analysis was to evaluate the effectiveness and adverse effects of palonosetron in the prevention of postoperative nausea and vomiting (PONV). DESIGN: A meta-analysis using a systematic search strategy was performed. METHODS: A meta-analysis of randomized controlled clinical trials was performed to compare palonosetron with first-generation 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA) or placebo to prevent PONV. Fixed or random effect models were used to combine homogenous data. FINDINGS: A total of 10 randomized controlled clinical trials including 1,827 patients were identified. The data showed statistically significant differences in favor of palonosetron (0.075 mg) in the prevention of acute PONV (P < .00001) and delayed PONV (P < .002), reducing the risk of PONV by 49% and 51%, respectively. Subgroup analyses indicated significant differences in favor of palonosetron compared with placebo (P < .00001) or first-generation 5-HT3RA (P = .002). There were no significant differences in the occurrence of headache, dizziness, and constipation between palonosetron and control groups (P = .85, P = .22, and P = .30, respectively). CONCLUSIONS: The results of this meta-analysis suggest that intravenous palonosetron could become a prophylactic antiemetic 5-HT3RA in the prevention of PONV compared with first-generation 5-HT3RAs or placebo. No increased risk of side effects with palonosetron were found.

Is a dexamethasone-sparing strategy capable of preventing acute and delayed emesis caused by combined doxorubicin and paclitaxel for breast cancer? Analysis of a phase II trial.

OBJECTIVE: The effectiveness of palonosetron without delayed dexamethasone dosing against emesis was investigated in patients scheduled to receive the corticosteroid-containing combination of doxorubicin and paclitaxel (AT) for 3 cycles. METHODS: Chemo-naïve women with breast cancer receiving doxorubicin (60 mg/m(2)) and paclitaxel (200 mg/m(2)) were eligible. Patients received palonosetron 0.25 mg intravenously before chemotherapy, however, all patients also received a premedication consisting of prednisone (25 mg orally the evening before therapy) and hydrocortisone (250 mg intravenously just before paclitaxel). The primary end point was complete control (CC; no vomiting, no rescue anti-emetics, and no more than mild nausea) during the overall phase (days 1-5) following cycle 1. RESULTS: Seventy-six patients were enrolled and evaluable (median age 50 years). Fifty-six patients (74%; 95% CI 62-83%) achieved overall CC. Acute (day 1) and delayed (days 2-5) CC rates were 78 and 74%, respectively. No vomiting rates for the acute, delayed and overall phases were 85, 85 and 83%, respectively. An exploratory analysis showed only a small decrease in the probability of achieving CC between cycle 1 (74%) and cycle 3 (66%). CONCLUSION: The dexamethasone-sparing strategy prevented emesis in more than 70% of breast cancer patients receiving their initial cycle of AT chemotherapy.

Palonosetron plus dexamethasone in highly emetogenic chemotherapy: pooled data from two Phase III trials.

AIM: Data from two randomized trials were pooled to further characterize the effectiveness of palonosetron combined with dexamethasone in the setting of highly emetogenic chemotherapy. PATIENTS & METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Emerging treatments in chemotherapy-induced nausea and 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.

A phase III open-label study to assess safety and efficacy of palonosetron for preventing chemotherapy-induced nausea and vomiting (CINV) in repeated cycles of emetogenic chemotherapy.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: The extraordinary safety profile and maintenance of efficacy of 0.75 mg palonosetron combined with dexamethasone were demonstrated throughout repeated chemotherapy cycles.

Electrocardiographic findings of palonosetron in cancer patients.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Comparison of the effect of palonosetron versus tropisetron in prevention of vomiting in patients receiving high dose cisplatin-based chemotherapy].

OBJECTIVE: To evaluate the efficacy and toxicity of palonosetron for prevention of vomiting induced by high dose cisplatin-based chemotherapy. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.