Single Dose Of Palonosetron Research Articles

Does a single dose of palonosetron have any role in preventing acute chemotherapy-induced nausea and vomiting in pediatric osteosarcoma patients without dexamethasone? A randomized clinical trial.

Chemotherapy-induced nausea and vomiting (CINV) is a troublesome side-effect of chemotherapy in pediatric patients undergoing osteosarcoma treatment. In this context, the role of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists needs to be explored. To evaluate the superiority of single-dose palonosetron over granisetron in pediatric patients undergoing highly emetogenic chemotherapy (HEC) for osteosarcoma. In this double-blind, randomized study, pediatric patients were assessed in terms of acute nausea and vomiting following HEC for osteosarcoma. These children were assigned to group 1 (palonosetron) and group 2 (granisetron) without any other antiemetic prophylaxis. The primary outcome variable was the children's segment with a complete response (CR) during the acute phase of the 1st on-study chemotherapy cycle. The risk factors associated with the emesis were analyzed. The patients were followed up for the first 24 h after chemotherapy. A total number of 200 children were evaluated in terms of the response, and other factors that might alter the response were assessed in the 2 groups. These 200 children underwent 604 blocks of chemotherapy. Complete responses were documented in 83% and 72% of children receiving palonosetron and granisetron, respectively, during the acute phase. Only dexamethasone, used as a rescue medication, was found to be a significant risk factor that predisposed to the response (p < 0.05). Single-dose palonosetron is an effective alternative to granisetron for preventing CINV in children receiving HEC for osteosarcoma.

Palonosetron A Promising New Prophylactic for PONV

Aim and Objective- The aim of the study was to evaluate the efficacy of palonosetron 0.075 mg for prevention of postoperative nausea and vomiting (PONV) in patients undergoing middle ear surgeries in comparison with ondansetron. Methods - In this prospective observational study, 70 healthy patients who were undergoing elective middle ear surgeries were divided into 2 groups: Group P (palonosetron 0.075 mg i.v., n = 35) and group C (ondansetron 8 mg i.v., n = 35). The drugs were given 5 minutes before induction of anaesthesia. The incidence of nausea, vomiting, retching, severity of nausea, use of recue antiemetic and incidence of complete response were evaluated. Results - The incidence of nausea, vomiting and severity of nausea was lower in palonosetron group as compared to ondansetron group but this difference was not statistically different. The incidence of use of rescue antiemetic (5.71% vs 23.53%) was significantly lower in palonosetron group. The incidence of complete response was higher in palonosetron group (88.87% vs 68.57%) but the difference was not statistically significant. Conclusion- The prophylactic intravenous administration of single dose of palonosetron 0.075 mg is not more effective in controlling postoperative nausea and vomiting as compared to ondansetron 8 mg in middle ear surgery.

Abstract P5-11-03: Difference between 1st and 2nd generation serotonin receptor antagonists in triplet antiemetic therapy for highly emetogenic chemotherapy in breast cancer patients – according to recent multi-institutional double-blind randomized clinical research on the AC regimen

Abstract &amp;lt;Background&amp;gt; The information presented herein extends our recent study of TTT (Trial for Triplet Antiemetic Therapy). One of our main clinical questions has been whether a 2nd generation serotonin receptor antagonist (5-HT3ra) would be superior to 1st generation 5-HT3ra when administering triplet antiemetic therapy for the prevention of chemotherapy induced nausea &amp; vomiting (CINV), since a prior Japanese trial demonstrated palonosetron to be superior to granisetron for controlling the delayed phase of CINV induced by highly emetogenic chemotherapy (HEC) and to doublet antiemetic therapy including dexamethasone for anthracycline and cyclophosphamide containing regimens (AC). &amp;lt;Objectives&amp;gt; In this study, we assessed the efficacies of 1st and 2nd generation 5-HT3ra agents for use as triplet antiemetic therapy for AC, by monitoring CINV, focusing especially daily CR in the delayed phase. &amp;lt;Material and method&amp;gt; Between 2012 and 2015, 491 women with breast cancer receiving AC were recruited from 11 institutions in Japan, and randomly assigned to either single-dose palonosetron (0.75mg) or granisetron (40μg/kg) prior to chemotherapy on day 1, both with dexamethasone (9.9 mg intravenously) and aprepitant (125mg orally) on day 1 followed by additional doses (80mg orally) on days 2 and 3. Age, institution and habitual alcohol intake were used as stratification factors. The primary endpoint was a complete response (CR). Statistical analysis was done by Mantel-Haenszel Method. This trial was registered with UMIN000007882. &amp;lt;Results&amp;gt; All 491 patients were included in efficacy analyses (ITT): 246 patients in the palonosetron group and 245 in the granisetron group. We previously reported that the difference in CR during the delayed phase, i.e. 24 hours after the administration of AC, did not reach statistical significance (53.8% vs 58.5%) in MASCC 2016. However, daily CR in the palonosetron group was much higher than that in the granisetron group after 48 hours. &amp;lt;Conclusions&amp;gt; Palonosetron showed better efficacy in controlling CINV during the late period of the delayed phase, i.e. 48 hours after AC administration, than granisetron as triplet antiemetic therapy for AC. &amp;lt;Considerations&amp;gt; The pattern of CINV reportedly shows two peaks including an acute phase caused by serotonin and a delayed phase caused by substance P, though the pattern of CINV with triplet antiemetic therapy administration might be different if the suppression of each of these peaks were to be achieved more efficiently. CINV may not be divided into two phases in the future, or the borderline area between the acute and delayed phases may require revision. The analysis of the late period of the delayed phase was ad hoc in this trial. However, when conducting studies related to CINV, it might be worthwhile to revise the borderline area between the two phases of CINV to facilitate elucidating the mechanisms underlying this potentially debilitating side effect of chemotherapy. Citation Format: Ogata H, Saito M, Tsuneizumi M, Kutomi G, Hosoya K, Kawai Y, Sugizaki K, Katsumata N, Senuma K, Kitabatake T, Suda M, Uomori T, Miura K, Kurata M, Nitta Y, Yonemoto N, Matsuoka J. Difference between 1st and 2nd generation serotonin receptor antagonists in triplet antiemetic therapy for highly emetogenic chemotherapy in breast cancer patients – according to recent multi-institutional double-blind randomized clinical research on the AC regimen [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-11-03.

Single-dose palonosetron and dexamethasone in preventing nausea and vomiting induced by moderately emetogenic chemotherapy in breast and colorectal cancer patients.

Palonosetron, a unique second-generation 5-HT3 receptor antagonist, has been demonstrated to control emesis related to chemotherapy-induced nausea and vomiting (CINV). The aim of this study was to evaluate the efficacy and tolerability of palonosetron followed by a single dose of dexamethasone in patients with breast cancer (BC) or colorectal cancer (CRC) receiving moderate emetogenic chemotherapy (MEC). Chemotherapy-naive BC and CRC patients were given MEC as adjuvant or first-line treatment. Palonosetron (0.25 mg IV) and dexamethasone (8 mg IV) were administered before chemotherapy on day 1. The primary endpoint was complete response (CR; no vomiting and no use of rescue medication) during the overall study period (days 1-5). The antiemetic response was evaluated during the acute (day 1) and delayed (days 2-5) phases. Sixty-eight patients were enrolled (median age 61 years, 56 females; BC = 40, CRC = 28). CR was observed in 46 of 68 patients (67.6%), while CR during the acute and delayed phases was 75.0% in each cancer group. The antiemetic regimen was well tolerated. A single administration of palonosetron and dexamethasone on day 1 in BC and CRC patients adequately controls CINV during the entire period of emetic risk.

Aprepitant plus palonosetron as salvage therapy for CINV induced by moderately emetogenic chemotherapy in cancer patients

Background Despite the efficacy of prophylaxis with serotonin type 3 (5-HT3) receptor antagonists, nausea and vomiting are still among the most common chemotherapy-induced toxicities. The aim of this study was to evaluate the efficacy of adding aprepitant in patients with chemotherapy-induced nausea and vomiting (CINV) refractory to prophylaxis with 5-HT3 receptor antagonists and dexamethasone. Patients and Methods Between January 2008 and November 2010, 51 patients (median age 59 years) with a variety of malignancies (breast cancer: 23; lung cancer: 12; sarcoma: 6; ovarian cancer: 3; other: 7) were enrolled. All patients were refractory to antiemetic therapy according to ASCO guidelines and developed at least grade 2 nausea and/or vomiting after the first chemotherapy course. Aprepitant was given at 125 mg on day 1 and 80 mg on days 2–3. Patients also received a single dose of palonosetron 250 μg on day 1 plus dexamethasone 12–20 mg at a constant dose. Results After addition of aprepitant, the number of patients with grade 3/4 nausea decreased from 31 (61%) to 4 (8%), and those with grade 2 nausea from 20 (39%) to 6 (12%) [both p

A Randomized Trial of Olanzapine and Palonosetron versus Infused Ondansetron for the Treatment of Chemotherapy Induced Nausea and Vomiting in Patients Undergoing Hematopoietic Stem Cell Transplantation

Background:Despite routine antiemetic administration during conditioning for hematopoietic stem cell transplantation (HSCT), breakthrough chemotherapy induced nausea and vomiting (CINV) can still be problematic. Recent studies in solid tumor therapy have demonstrated effectiveness of both olanzapine and the second generation 5HT3 receptor antagonist palonosetron in management of CINV. However, there remains little comparative data on efficacy of these agents, especially within HSCT.Aims:To compare the effectiveness of olanzapine and palonosetron to an ondansetron infusion (standard of care) for the treatment of breakthrough CINV in patients undergoing HSCT.Method:A randomized open-label prospective study was performed in HSCT patients suffering breakthrough CINV during conditioning despite standard prophylaxis with IV ondansetron 8mg TDS plus a single dose of oral aprepitant 165mg. Patients were randomised on a 1:1:1 basis to receive either ondansetron 32mg in 250ml normal saline as a continuous infusion over 24 hours, an olanzapine wafer 10mg once daily, or a single dose of palonosetron 0.25mg IV. All groups were allowed prn metoclopramide IV and / or lorazepam SL as rescue anti-nausea medication. Nausea score was graded from 0 (no nausea) to 100 (worst nausea) and recorded using a visual analogue scale (VAS). The primary endpoint was a composite outcome of no emesis, no use of rescue medication, and nausea score reduction of >50%. The secondary endpoint was nausea score reduction of >50%. Both endpoints were measure at 24 and 48hrs after initiation of the study treatment. Statistical analysis was conducted using a double-sided Fisher's exact test.Results:In total, 18, 22 and 22 patients were randomized to the ondansetron, olanzapine and palonosetron arms respectively. Overall 53% of patients had undergone autologous and 47% allogeneic HSCT. Conditioning regimens included high dose melphalan (200mg/m2) and BEAM for autologous HSCT and Cy / TBI and fludarabine / melphalan (melphalan 120mg/m2) for allogeneic protocols. A similar proportion of patients randomized to ondansetron versus olanzapine versus palonosetron received autologous versus allogeneic HSCT, with similar ratios of individual conditioning regimens included within each arm (p=NS for all comparisons). Patients' age, gender and other risk factors such as history of CINV were also similar between arms (p=NS for all comparisons). The primary endpoint was achieved in 6%, 45% and 18%, and 6%, 64% and 18% of ondansetron versus olanzapine versus palonosetron patient groups at 24 and 48hrs respectively. Overall olanzapine was significantly more effective at controlling breakthrough CINV compared to ondansetron at both 24 and 48hrs (p=0.011 and 0.0002 respectively). Olanzapine was also more effective than palonosetron at 48hrs (p=0.005). The secondary outcome was observed in 17%, 60% and 62%, and 35%, 71% and 43% of ondansetron versus olanzapine versus palonosetron patient groups at 24 and 48hrs respectively. Again, olanzapine was superior to ondansetron at controlling nausea at both 24 and 48hrs (p=0.0009 and p=0.048 respectively). However, there was no significant difference between olanzapine and palonosetron in reduction of nausea score >50% at either time point. Palonosetron was superior to ondansetron at nausea control at 24 (p=0.008) but not at 48hrs. Serious adverse drug reactions were not reported in any arms, and median duration from stem cell infusion to the engraftment was 13 days, 13 days and 14 days for ondansetron, olanzapine and palonosetron arms respectively (p=NS).Conclusions:When compared to ondansetron infusion and a single dose of palonosetron, daily olanzapine is superior treatment of breakthrough CINV in patients undergoing HSCT. A single dose of palonosetron does not significantly reduce emesis but is effective for the treatment of nausea up to 24 hours. Further studies are required to determine the ideal dosing frequency of palonosetron. DisclosuresOff Label Use: Olanzapine is used as an antiemetic, which is widely accepted..

Comparison of antiemetic efficacy and safety of palonosetron vs ondansetron in the prevention of chemotherapy-induced nausea and vomiting in children.

Chemotherapy-induced nausea and vomiting (CINV) in children is a major side effect despite the use of combination antiemetic drugs. To compare the efficacy and safety profile of palonosetron, a second-generation 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, with ondansetron in the prevention of CINV in children. A prospective, randomized, crossover study was conducted in patients aged 2-18 years. 160 chemotherapy cycles, consisting of chemotherapy drugs with moderate- and high-emetogenic potential, were studied. The study group received a single dose of intravenous (IV) palonosetron 5 mcg/kg, and the standard group received IV ondansetron 5 mg/m2 every 8 hours while receiving chemotherapy. The patients were observed for vomiting, use of rescue antiemetic medications, and nausea from Day 1 0-72 hours after completion of each chemotherapy cycle. All adverse events during the study period were recorded. The overall percentage of patients with complete response (CR) in the palonosetron and ondansetron groups were 60% and 56.2%, respectively (𝑃 = .631). The CR rates in the palonosetron and ondansetron groups were 75% and 70%, respectively, in the acute phase (𝑃 = .479), and 68.8% and 65%, respectively, in the delayed phase (𝑃 = .614). There was no statistically significant difference in the CR rates cross both groups. A single dose of palonosetron is noninferior to ondansetron in the prevention of CINV in children and can be considered as an alternative antiemetic drug. There was no significant difference in adverse effects between the palonosetron and ondansetron group.

“A comparison of ondansetron and palonosetron for prevention of post-operative nausea and vomiting in patients undergoing elective abdominal surgeries under general anaesthesia” A randomized double blind study

Background: Post-operative nausea and vomiting (PONV) is commonly seen in female patients undergoing abdominal surgeries under general anaesthesia. In this randomized double blind prospective study, efficacy of ondansetron and palonosetron for prevention of PONV following abdominal surgeries under general anaesthesia was compared. Methods: 60 female patients undergoing elective abdominal surgery were randomly allocated to one of the two groups of 30 patients each. Group O patients received injection Ondansetron 4mg and Group P patients received injection Palonosetron 75mcg intravenously 15 minutes before induction. All episodes of PONV within 72 hours after induction of anaesthesia were recorded. Statistical Analysis: Statistical analysis was done using two sample t test. Results: The incidence of complete response (no PONV, no rescue medication required) during 0-6 hours in post-operative period was 93.33% in patients of group O and 86.67% in patients of group P. But the incidence of complete response during 624 hrs of post-operative period was only 73.33% in patients of group O while it was 93.33% in patients of group P. During 2448 hours in postoperative period incidence of complete response was only 66.67% in group O while it was 96.67 % in group P. And during 48-72 hrs in postoperative period incidence of complete response was 86.67% in patients of group O and 96.67% in patients of group P. Rescue antiemetic in the form of inj. Metoclopramide was given in the patients who had vomiting. Conclusion: Single dose of Palonosetron was more effective for prevention of nausea and vomiting in comparison to Ondansetron after 6 hrs in post-operative period in abdominal surgeries.

Antiemetic efficacy of single-dose palonosetron and dexamethasone in patients receiving multiple cycles of multiple day-based chemotherapy

IntroductionThe 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).MethodsPatients 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.ResultsFifty 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.ConclusionsThis 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.

Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate

High dose methotrexate (HD-MTX), used in the treatment of children with acute lymphoblastic leukemia (ALL), is moderately emetogenic. First generation 5-HT(3) receptor antagonists are effective prophylactic agents but require multiple administrations. Palonosetron has a half life of 36-42 hours and has higher affinity and selectivity to the 5-HT(3) receptor. Adult studies have demonstrated that palonosetron is both more effective and require fewer administrations than first generation 5-HT(3) receptor antagonists. The purpose of this study was to examine the effect of a single dose of palonosetron (5 µg/kg) for the prevention of chemotherapy-induced nausea and vomiting in children 18 years of age with ALL treated with HD-MTX, 5 g/m(2). Between January 2010 and December 2010, 138 courses, originating from 53 children, were included from four Danish Childhood Cancer Centers. Information regarding emetic episodes, rescue therapy, and nausea were recorded prospectively on questionnaires. Complete response (no emesis and no rescue therapy) was achieved in 84.1% of courses during the acute (0-24 hours post-chemotherapy) and in 60.1% during the delayed phase (24-66 hours post-chemotherapy). 92.0% of courses were free of emesis during the acute, and 86.2% were free of emesis during the delayed phase. 76.8% of courses were free of nausea during the acute, and 78.3% were free of nausea during the delayed phase. A single dose of palonosetron--without concomitant corticosteroid--was effective in preventing both acute and delayed phase CINV in majority of children with ALL treated with HD-MTX.

Olanzapine Versus Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Randomized Phase III Trial

The purpose of the study was to compare the effectiveness of olanzapine (OLN) and aprepitant (APR) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy. A phase III trial was performed in chemotherapy-naive patients receiving cisplatin ≥ 70 mg/m(2) or cyclophosphamide ≥ 500 mg/m(2) and doxorubicin ≥ 50 mg/m(2), comparing OLN to APR in combination with palonosetron (PAL) and dexamethasone (DEX). The OLN, PAL, DEX (OPD) regimen was 10 mg of oral OLN, 0.25 mg of IV PAL, and 20 mg of IV DEX prechemotherapy, day 1, and 10 mg/day of oral OLN alone on days 2-4 postchemotherapy. The APR, PAL, DEX (APD) regimen was 125 mg of oral APR, 0.25 mg of IV PAL, and 12 mg of IV DEX, day 1, and 80 mg of oral APR, days 2 and 3, and 4 mg of DEX BID, days 2-4. Two hundred fifty-one patients consented to the protocol and were randomized. Two hundred forty-one patients were evaluable. Complete response (CR) (no emesis, no rescue) was 97% for the acute period (24 hours postchemotherapy), 77% for the delayed period (days 2-5 postchemotherapy), and 77% for the overall period (0-120 hours) for 121 patients receiving the OPD regimen. CR was 87% for the acute period, 73% for the delayed period, and 73% for the overall period in 120 patients receiving the APD regimen. Patients without nausea (0, scale 0-10, MD Anderson Symptom Inventory) were OPD: 87% acute, 69% delayed, and 69% overall; APD: 87% acute, 38% delayed, and 38% overall. There were no grade 3 or 4 toxicities. CR and control of nausea in subsequent chemotherapy cycles were equal to or greater than cycle 1 for both regimens. OPD was comparable to APD in the control of CINV. Nausea was better controlled with OPD. In this study, OLN combined with a single dose of DEX and a single dose of PAL was very effective at controlling acute and delayed CINV in patients receiving highly emetogenic chemotherapy. CR rates were not significantly different from a similar group of patients receiving highly emetogenic chemotherapy and an antiemetic regimen consisting of APR, PAL, and DEX.

Single dose palonosetron and dexamethasone in preventing nausea and vomiting induced by high emetogenic ABVD regimen in Hodgkin Lymphoma patients

To evaluate the efficacy of a new agent, palonosetron, in Hodgkin Lymphoma patients treated with ABVD regimen. Complete response during the overall phase of the first ABVD cycle, was the primary endpoint. Secondary end points were: emesis-free patients and use of rescue medication during the acute and overall phases. From January 2008 to February 2009 36 patients were enrolled. The primary endpoint (CR 0–120h) was achieved by 55.6% patients. In conclusion our study demonstrated that a single dose of palonosetron plus a single dose of dexamethasone was effective in preventing CINV in patients treated with ABVD regimen.

Single-dose palonosetron and dexamethasone in preventing nausea and vomiting induced by moderately emetogenic chemotherapy in breast and colorectal cancer patients

Palonosetron, a unique second-generation 5-HT3 receptor antagonist, has been demonstrated to control emesis related to chemotherapy-induced nausea and vomiting (CINV). The aim of this study was to evaluate the efficacy and tolerability of palonosetron followed by a single dose of dexamethasone in patients with breast cancer (BC) or colorectal cancer (CRC) receiving moderate emetogenic chemotherapy (MEC). Chemotherapy-naive BC and CRC patients were given MEC as adjuvant or first-line treatment. Palonosetron (0.25 mg IV) and dexamethasone (8 mg IV) were administered before chemotherapy on day 1. The primary endpoint was complete response (CR; no vomiting and no use of rescue medication) during the overall study period (days 1-5). The antiemetic response was evaluated during the acute (day 1) and delayed (days 2-5) phases. Sixty-eight patients were enrolled (median age 61 years, 56 females; BC = 40, CRC = 28). CR was observed in 46 of 68 patients (67.6%), while CR during the acute and delayed phases was 75.0% in each cancer group. The antiemetic regimen was well tolerated. A single administration of palonosetron and dexamethasone on day 1 in BC and CRC patients adequately controls CINV during the entire period of emetic risk.

Palonosetron Versus Other 5-HT 3 Receptor Antagonists for Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients With Cancer on Chemotherapy in a Hospital Outpatient Setting

Background 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). Objective 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. Methods 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. Results 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. Conclusions 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.

Single-dose palonosetron for prevention of chemotherapy-induced nausea and vomiting in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy containing steroids: results of a phase II study from the Gruppo Italiano per lo Studio dei Linfomi (GISL)

PurposeThe control of nausea and vomiting induced by chemotherapy is paramount for overall treatment success in cancer patients. Antiemetic therapy during chemotherapy in lymphoma patients generally consists of anti-serotoninergic drugs and dexamethasone. The aim of this trial was to evaluate the efficacy of a single dose of palonosetron, a second-generation serotonin type 3 (5-HT3) receptor antagonist, in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy (MEC) containing steroids.MethodsPatients received a single intravenous bolus of palonosetron (0.25 mg) before administration of chemotherapy. Complete response (CR) defined as no vomiting and no rescue therapy during overall phase (0–120 h) was the primary endpoint. Complete control (CC) defined as CR and only mild nausea was a secondary endpoint.ResultsEighty-six evaluable patients entered in the study. A CR was observed in 74 patients (86.0%) during the overall phase; the CR during the acute (0–24 h) and delayed (24–120 h) phases was 90.7% and 88.4%, respectively. CC was 89.5% during the acute and 84.9% during the delayed phase; the overall CC was 82.6%.ConclusionsThis was the first trial, which demonstrated the efficacy of a single dose of palonosetron in control CINV in patients with aggressive non-Hodgkin’s lymphoma receiving MEC regimen containing steroids.

Palonosetron for the prevention of chemotherapy-induced nausea and vomiting in glioblastoma patients treated with temozolomide: a phase II study

Chemotherapy-induced nausea and vomiting (CINV) is a side effect related to administration of the adjuvant temozolomide (TMZ) in patients affected by glioblastoma. After chemoradiotherapy, adjuvant TMZ is administered as an oral multiple-day regimen, and TMZ-associated CINV may interfere with the continuation of chemotherapy, with potentially negative consequences on clinical efficacy. The aim of the present study was to investigate the efficacy of palonosetron for prevention of CINV-induced by adjuvant TMZ. From March 2007 to August 2008, 33 patients with confirmed glioblastoma and eligible for adjuvant treatment with TMZ were enrolled in the study. All patients with responding or stable disease after concomitant radiotherapy plus daily TMZ (75 mg/m(2)) received a single i.v. bolus 0.25 mg of palonosetron 30 min before the beginning of adjuvant TMZ (150-200 mg/m(2)/day for five consecutive days every 4 weeks). The primary endpoint was the percentage of patients with complete response (CR), defined as no emetic episodes and no rescue medication during the overall phase (0-168 h). Secondary endpoints included CR during the 0-120 h and 0-168 h phases and complete control (CC; CR and no more than mild nausea) during the 0-120 h, 120-168 h, and 0-168 h phases. Thirty-three patients were enrolled in the study (median age 57.6 years, 23 male and 10 female, median Karnofsky Performance Status = 80). Each patient was receiving fixed doses of dexamethasone (range 2-8 mg/day). CR in the 0-120 h, 120-168 h, and 0-168 h phases was seen in 91% of patients. CC was observed in 88%, 91%, and 88% of cases during the 0-120 h, 120-168 h, and 0-168 h phases, respectively. Anti-emetic prophylaxis with palonosetron was well tolerated and the most frequent adverse event was grade 1-2 headache reported by seven patients (21%). A single dose of palonosetron before the initiation of multiple oral doses of TMZ, in patients on treatment with steady doses of dexamethasone, provides a high protection against CINV throughout the overall phase (0-168 h). The pharmacological profile of palonosetron, compared to first-generation 5-HT3 receptor antagonists, may have an impact on its clinical efficacy.

Palonosetron in Prevention of Nausea and Vomiting After Highly Emetogenic Chemotherapy Before Haematopoietic Stem Cell Transplantation—Single Center Experience

A clinical study of palonosetron was performed to evaluate its efficacy in preventing both acute and delayed emesis after high-dose chemotherapy (HDC) before hematopoietic stem cell transplantation (HSCT) using a historical control group of patients treated with ondansetron as the comparative drug. Among the 46 evaluated patients 20 with lymphoma received BEAM as the conditioning regimen; 16 has relapsed germ cell tumors treated with CARBOPEC; and 10 with acute myeloid leukemia received BuCY. Increasing severity of nausea was evaluated according to the following 4-grade scale: none (no nausea); mild (slight nausea but no disruption to daily activities); moderate (nausea and some disruption to daily activities); and severe (extreme nausea and severe disruption to daily activities). The emetic response rate was evaluated using the criteria: complete (no emetic episode); major (1-2 episodes); minor (3-5 episodes); and failure (>5 episodes). The response rate of the study drugs was evaluated by the following 4-grade scale based on the condition of nausea and vomiting: highly effective, moderately effective, slightly effective, and not effective. Patients treated with palonosetron showed significantly greater response rates than those receiving ondansetron during the both the acute and the delayed phases: highly and moderately effective: acute phase 15% versus 5% CARBOPEC; 70% versus 35% BEAM and 32% versus 20% BuCY; delayed phase: 60% versus 30% BuCY; 100% versus 50% BEAM and 25% versus 10% CARBOPEC. Single-dose palonosetron was more effective than ondansetron treatment to prevent acute and delayed nausea and vomiting following HDC before HSCT.

3078 Phase II study: single dose of palonosetron plus dexamethasone to control nausea, vomiting in patients treated with moderately emetogenic chemotherapy

3078 Phase II study: single dose of palonosetron plus dexamethasone to control nausea, vomiting in patients treated with moderately emetogenic chemotherapy

Single dose of palonosetron plus dexamethasone to control nausea, vomiting and to warrant an adequate food intake in patients treated with highly emetogenic chemotherapy (HEC). Preliminary results

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.

Palonosetron—A Single-Dose Antiemetic Adjunct for Hepatic Artery Radioembolization: A Feasibility Study

Nausea and vomiting may occur in a significant minority of patients following hepatic artery embolization with yttrium-90 spheres (K. T. Sato et al. Radiology 247:507-515, 2008). This encumbers human and economic resources and undercuts the assertion that it is as a well-tolerated outpatient treatment. A single intravenous dose of palonosetron HCl was administered before hepatic artery embolization with yttrium-90 spheres to ameliorate posttreatment nausea and vomiting, in 23 consecutive patients. The patients were discharged the day of procedure on oral antiemetics, steroids, and blockers of gastric acid release. All patients had clinical and laboratory evaluation at 2 weeks after the procedure. The data were gathered and reviewed retrospectively. At 2-week follow-up, none reported significant nausea, vomiting, additional antiemetic use, need for parenteral therapy, hospital readmission, or palonosetron-related side effects. All patients recovered from postembolization symptoms within a week after treatment. In conclusion, this retrospective study suggests that single-dose palonosetron is feasible, safe, and effective for acute and delayed nausea and vomiting in this group of patients. The added cost may be offset by benefits.