Control Of Vomiting Research Articles

Emesis control by aprepitant in children and adolescents with chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) is a feared adverse reaction during cancer treatment. Aprepitant has shown to be effective for CINV in adults, but little is known on its effect in pediatrics. So far, the drug is not licensed in this population. To investigate efficacy of aprepitant in children and young adolescents with high or moderate emetogenic courses, with uncontrollable emesis in previous cycles. Retrospective, observational study in children and adolescents treated with aprepitant at Ghent University Hospital, Belgium. Antiemetic regimens and emesis control were analyzed. Twenty patient charts representing 104 chemotherapy cycles were reviewed. Complete vomiting control was observed in 10 patients (50 %), representing 89/104 (85.6 %) episodes. Incomplete vomiting control was observed in 10 patients (50 %), representing only 15 episodes (14.4 %). Of these episodes with incomplete vomiting control, 6 were in acute phase (40 %), 7 in delayed phase (46.7 %) and 2 in both acute and delayed phase (13.3 %). Aprepitant might be effective in preventing or reducing vomiting in children. When combined with standard antiemetics, aprepitant was well tolerated. In attendance of results of on-going international clinical trials, our results encourage us to continue the use of aprepitant after failure of emesis control in previous cycles.

Hydroxyzine distribution in postmortem cases and potential for redistribution

Hydroxyzine is an antihistaminic with sedative properties used in the control of anxiety and emesis. Peripheral blood hydroxyzine concentrations are compared to central blood and liver concentrations in 10 medical examiner cases. Specimens were initially screened for alcohol and simple volatiles by GC-FID headspace analysis, ELISA for drugs of abuse, and alkaline drugs by GC/MS. Hydroxyzine, when detected by the alkaline drug screen, was subsequently confirmed and quantified by a specific GC-NPD procedure. Data suggest that postmortem peripheral blood hydroxyzine concentrations may be considered therapeutic to at least 0.24mg/L and corresponding liver concentrations to at least 4.9mg/kg. Hydroxyzine concentrations ranged 0.07–3.0mg/L in peripheral blood, 0.04–3.8mg/L in central blood, and 0.88–55mg/kg in liver. Hydroxyzine central blood to peripheral blood ratios averaged 0.92±0.25 (±standard deviation; N=6). Liver to peripheral blood ratios, on the other hand, were higher and averaged 13.8±6.2 (±standard deviation; N=10). Given that a liver to peripheral blood ratio less than 5 is consistent with little to no postmortem redistribution while exceeding 20–30 is indicative of propensity for significant postmortem redistribution, these data suggest that hydroxyzine is prone to a moderate degree of postmortem redistribution.

Peripheral and central NK1 receptors in emesis control in Suncus murinus

Brain penetrant tachykinin NK1 receptor antagonists are known to reduce cisplatin‐induced emesis in ferrets. In the present studies, we investigate the role of central versus peripheral NK1 receptors in the mechanism of emesis in S. murinus. R116301 was selected as a reference brain penetrant NK1 receptor antagonist, and R115614 was used as a peripherally restricted antagonist; both have similar affinity for S. murinus NK1 receptors (PA2~8) and in vivo potency to reduce substance P‐induced plasma extravasation (ID50 ~2.9 μmol/kg). Drugs or vehicle were administered s.c, or i.c.v. 30 min prior to nicotine (30.7 μmol/kg, s.c.), copper sulphate.5H2O (480.6 μmol/kg, i.g.), or cisplatin (100 μmol/kg, i.p).Peripheral StudiesR116301 (23–53 mmol/kg, s.c) attenuated nicotine‐ and cisplatin‐induced emesis by 76 and 52 %, respectively (P<0.05). R115614 (30–70 mmol/kg, s.c) reduced copper sulphate‐ and cisplatin‐induced emesis by 75 and 50 %, respectively (P<0.05).Central StudiesR116301 (10–100 nmol, i.c.v.) antagonised nicotine‐induced emesis 89 % (P<0.05), while R115614 (100–500 nmol, i.c.v.) was incative (P>;0.05). In conclusion, centrally located tachykinin NK1 receptors play an important role in the emetic reflex but peripherally located NK1 receptors may also be involved in some causes of emesis.

Management of Chemotherapy-Induced Nausea and Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a serotonin 5-HT3 receptor antagonist, dexamethasone and a neurokinin 1 (NK1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second-generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity and a different mechanism of action than the first-generation 5-HT3 receptor antagonists appears to be the most effective agent in its class. Aprepitant, the first and only agent clinically available in the NK1 receptor antagonist drug class has been used effectively as an additive agent to the 5-HT3 receptor antagonists and dexamethasone to control CINV. Rolapitant and netupitant are other NK1 receptor antagonists that are currently in phase III clinical trials. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a US-FDA approved antipsychotic, has emerged in recent trials as an effective preventative agent for CINV, as well as a very effective agent for the treatment of breakthrough emesis and nausea. Clinical trials using gabapentin, cannabinoids and ginger have not been definitive regarding their efficacy in the prevention of CINV. Additional studies are necessary for the control of nausea and for the control of CINV in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.

The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy

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

A Review of the Prevention of Nausea and Vomiting Induced by Chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles and patient risk factors significantly influence CINV. The use of a combination of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, dexamethasone and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second-generation 5-HT3 receptor antagonist with a unique mechanism of action, appears to be the most effective agent in its class. Aprepitant, the only agent clinically available in the drug class of NK-1 receptor antagonists, has been used effectively as an additive agent to the 5-HT3 receptor antagonists and dexamethasone. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a US Food and Drug Administration-approved antipsychotic, has emerged in recent trials as effective for the prevention of chemotherapy-induced emesis and nausea and for the treatment of breakthrough emesis and nausea. Additional studies are necessary for the control of nausea and for the control of CINV in the clinical settings of multi-day chemotherapy and bone marrow transplantation.

Association of ABCB1 Polymorphisms with the Antiemetic Efficacy of Granisetron plus Dexamethasone in Breast Cancer Patients

Resistance to antiemetic treatment with 5-hydroxytryptamine 3 receptor antagonists is a problem, with 20-30% of patients showing unsatisfactory responses. Efflux transport by P-glycoprotein, encoded by the ATP-binding cassette ABCB1 gene in the blood-brain barrier, has been the suggested resistance mechanism. We evaluated the association between the antiemetic efficacy of granisetron plus dexamethasone and ABCB1 polymorphisms 3435C>T and 2677G>T/A. Sixty-four breast cancer patients treated with doxorubicin plus cyclophosphamide were evaluated for their responses to antiemetic therapy. Genotyping of patient DNA samples for ABCB1 single nucleotide polymorphisms was performed; the genotypes were then investigated for their association with the efficacy of prophylactic antiemetics. The acute phase complete response rate was 83% in GG subjects (n = 12), and 69% (n = 35) and 41% (n = 17) in heterozygous and homozygous carriers of the 2677T/A allele, respectively (p = 0.047). The ABCB1 2677 TT genotype group showed significantly lower rates of complete control of acute emesis than the group with GG genotypes (p = 0.045). No significant association with complete response was found for 3435C>T (p = 0.190). ABCB1 polymorphisms may influence the extent of acute emesis control in granisetron-treated patients, making the ABCB1 genotype a predictor of prophylactic antiemetic response.

Can treatment with Cocculine improve the control of chemotherapy-induced emesis in early breast cancer patients? A randomized, multi-centered, double-blind, placebo-controlled Phase III trial

BackgroundChemotherapy induced nausea and vomiting (CINV) remains a major problem that seriously impairs the quality of life (QoL) in cancer patients receiving chemotherapy regimens. Complementary medicines, including homeopathy, are used by many patients with cancer, usually alongside with conventional treatment. A randomized, placebo-controlled Phase III study was conducted to evaluate the efficacy of a complex homeopathic medicine, Cocculine, in the control of CINV in non-metastatic breast cancer patients treated by standard chemotherapy regimens.MethodsChemotherapy-naïve patients with non-metastatic breast cancer scheduled to receive 6 cycles of chemotherapy including at least three initial cycles of FAC 50, FEC 100 or TAC were randomized to receive standard anti-emetic treatment plus either a complex homeopathic remedy (Cocculine, registered in France for treatment of nausea and travel sickness) or the matching placebo (NCT00409071 clinicaltrials.gov). The primary endpoint was nausea score measured after the 1st chemotherapy course using the FLIE questionnaire (Functional Living Index for Emesis) with 5-day recall. Secondary endpoints were: vomiting measured by the FLIE score, nausea and vomiting measured by patient self-evaluation (EVA) and investigator recording (NCI-CTC AE V3.0) and treatment compliance.ResultsFrom September 2005 to January 2008, 431 patients were randomized: 214 to Cocculine (C) and 217 to placebo (P). Patient characteristics were well-balanced between the 2 arms. Overall, compliance to study treatments was excellent and similar between the 2 arms. A total of 205 patients (50.9%; 103 patients in the placebo and 102 in the homeopathy arms) had nausea FLIE scores > 6 indicative of no impact of nausea on quality of life during the 1st chemotherapy course. There was no difference between the 2 arms when primary endpoint analysis was performed by chemotherapy stratum; or in the subgroup of patients with susceptibility to nausea and vomiting before inclusion. In addition, nausea, vomiting and global emesis FLIE scores were not statistically different at any time between the two study arms. The frequencies of severe (Grade ≥ 2) nausea and vomiting were low in our study (nausea: P: 17.6% vs C: 15.7%, p=0.62; vomiting: P: 10.8% vs C: 12.0%, p=0.72 during the first course).ConclusionThis double-blinded, placebo-controlled, randomised Phase III study showed that adding a complex homeopathic medicine (Cocculine) to standard anti-emetic prophylaxis does not improve the control of CINV in early breast cancer patients.

Aprepitant and control of emesis induced by 5-day chemotherapy

Addition of aprepitant, an NK-1 receptor antagonist, to dexamethasone and a 5-HT3 receptor antagonist contributes substantially to emetic control in patients receiving 5-day cisplatin-containing chemotherapy, a new trial shows. Some needs in antiemetic therapy remain unmet, including control of emesis with multiple-day chemotherapy and control of nausea.

Effect of Hydroxyzine in Controlling Acute Chemotherapy-Induced Vomiting in Children: A Randomised Trial

ABSRACT Nausea and vomiting are one of the most important side effects of chemotherapy. Psychological factors such as anxiety, fear and negative moods have significant role in the chemotherapy induced emesis. Each chemotherapy course cause state anxiety like an invasive medical procedure. Therefore, we aimed to evaluate the effect of addition a sedative-anxiolytic agent to a 5-HT3 receptor antagonist in improving the control of chemotherapy induced emesis. Seventy chemotherapy courses in 18 children who received at least one highly emotogenic drugs were interpreted. Courses were randomly assigned to receive ondansetron (group I) or ondansetron plus hydroxyzine as a sedative agent (group II). Control of emesis was evaluated according to Soukop-Smith criteria. Performance of patients and degree of symptoms was assessed by using Lansky Play-Performance Scale and the Symptom Distress Scale, respectively. The complete and major control rate of acute emesis in group II (56%) was higher than group I (22%) (p= 0.006). The effect of combination antiemetic therapy was more obvious in female than male (p= 0.03), and in patients whose age greater than 10 years (p= 0.02). The mean play performance scale and symptom distress scale score were similar in two groups, before the chemotherapy course. After completion of course, play performance and symptom distress scale score were significantly better in group-II than that of group-I. Patients and parents in group-II declared significantly better sleeping quality, appetite, activity and mood than group-I. Hydroxyzine may enhance the activity of ondansetron in controlling acute chemotherapy-induced emesis and provided a better performance and lesser symptom distress.

The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy.

9064 Background: Olanzapine (OLN) has been shown to be a safe and effective agent for the prevention of CINV. OLN may also be an effective rescue medication for patients who develop breakthrough CINV despite having received guideline directed CINV prophylaxis. Methods: A double blind, randomized phase III trial was performed for the treatment of breakthrough CINV in chemotherapy naïve patients receiving highly emetogenic chemotherapy (HEC) (cisplatin, &gt;70 mg/m2, or doxorubicin, &gt;50 mg/m2 and cyclophosphamide, &gt; 600mg/m2 ) comparing OLN to Metoclopramide (METO). Patients who developed breakthrough emesis or nausea despite prophylactic dexamethasone (12 mg IV), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) pre chemotherapy and dexamethasone (8 mg p.o. daily, days 2-4) post chemotherapy were randomized to receive OLN, 10 mg orally daily for three days or METO, 10 mg orally TID for three days. Patients were monitored for emesis and nausea for the 72 hours after taking OLN or METO. Eighty patients (median age 56 yrs, range 38-79; 43 females; ECOG PS 0,1) consented to the protocol and all were evaluable. Results: During the 72 hour observation period, 30 of 42 (71%) patients receiving OLN had no emesis compared to 12 of 38 (32%) patients with no emesis for patients receiving METO (p&lt;0.01). Patients without nausea (0, scale 0-10, M.D. Anderson Symptom Inventory) during the 72 hour observation period was: OLN: 67% (28 of 42); METO 24% (9 of 38) (p&lt;0.01). There were no Grade 3 or 4 toxicities. Conclusions: OLN was significantly better than METO in the control of breakthrough emesis and nausea in patients receiving HEC.

The effect of continuous exposure to serotonin receptor antagonism on delayed emesis: An analysis of 1,535 patients in two randomized clinical trials with granisetron (G), APF530, and palonosetron (palo).

e19635 Background: Serotonin-type 3 receptor antagonists (5HT3RA) are recommended by all evidence-based guideline groups. Controversies remain over the role of 5HT3RA in delayed emesis and in dosages. This analysis was conducted to examine if: 1) serotonin antagonism helps prevent delayed emesis, 2) length of continuous exposure to a 5HT3RA impacts efficacy, and 3) higher doses of a 5HT3RA influence results. Palo, a 5HT3RA with a long half life, was superior to older 5HT3RA agents in single agent trials and to G + dexamethasone (dex) in a combination trial in untreated patients (pts) (Saito et al, Lancet Oncol 2009 – Trial 1). APF530 is an extended release formulation of 2% G (500mg = 10 mg of G) in a biodegradable polymer, which with dex showed non-inferiority with palo + dex in a mix of untreated and treated pts (Grous et al, ASCO 2009 – Trial 2). Methods: We analyzed results of only untreated pts from Trial 2 so that the population was similar to those in Trial 1 (previously untreated, highly or moderately emetic chemo and received dex + single administration of a 5HT3RA). This allows comparison, over 2 trials, of G, APF530, palo at 0.25 mg and 0.75 mg. Results: See table. All three groups treated with the long acting 5HT3RA (palo at 0.25 mg or 0.75 mg) or the extended release 5HT3RA (APF530) had similar efficacy in complete control of acute, delayed, or overall 5-day emesis. Only the short acting G was associated with poorer results, in delayed and overall 5-day control. Conclusions: This analysis indicates that 1) continuous exposure to 5HT3RA as a long acting agent or as an extended release formulation provide better emetic control than the standard 5HT3RA granisetron, even with added dex, and 2) similar results were found with palo at 0.25 mg and 0.75 mg. These results indicate a role for serotonin antagonism in delayed emesis provided the patient receives continuous exposure of a 5HT3RA agent. [Table: see text]

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

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

Potential role of GLP‐1 receptors in emesis control in Suncus murinus (house musk shrew)

Studies in rodents and ferrets have shown that GLP‐1 containing neurons connect the brainstem emetic centres with forebrain areas involved in nausea and feeding. The aim of the present study was to use Suncus murinus, a species commonly used in emesis research, to investigate the mechanism of GLP‐1‐induced emesis and to examine if GLP‐1 antagonists have anti‐emetic properties. In conscious freely moving animals, the GLP‐1 receptor agonist, exendin‐4 (0.03–3 nmol, i.c.v.) induced emesis (P&lt;0.01) and c‐fos expression in the amygdala (P&lt;0.01), hypothalamus (P&lt;0.01) and brainstem (P&lt;0.001), but failed to modify amino acid levels in these areas (P&gt;0.05). The GLP‐1 receptor antagonist, exendin (9–39) (30 nmol, i.c.v.), antagonized emesis induced by exendin‐4, and the increases in c‐fos expression (P&lt;0.05). Conversely, ondansetron (3 μmol/kg, s.c.; P&gt;0.05) failed to reduce emesis. In other studies, exendin (9–39), antagonized emesis and c‐fos expression induced by the chemotherapeutic drug, cisplatin (30 mg/kg, i.p.; P&lt;0.05), but not nicotine (5 mg/kg, s.c.; P&gt;0.05), or copper sulphate pentahydrate (120 mg/kg, p.o.; P&gt;0.05). These findings suggest that central GLP‐1 may play a role in emesis control and that GLP‐1 receptors may represent a potential target for anti‐emetic development.

Antiemetic research: future directions

As a part of reviewing the Multinational Association of Supportive Care in Cancer (MASCC) antiemetic guidelines in Perugia in 2009, an expert group identified directions for future antiemetic research. In future trials, the prediction of nausea and vomiting may combine algorithms based on observed prognostic factors relating to the patient and the anticancer therapy, the identification of the genes that code for receptors, and pharmacogenetic studies of the metabolism of drugs. Design issues for future trials include standardising the emetic stimulus across studies and finding the minimum tolerated effective dose and schedule of an antiemetic. Also control of delayed emesis is not independent of the control of acute emesis. The full range of side effects and the impact on global quality of life scores should be part of the routine assessment of an antiemetic. With current high rates of control of acute vomiting, future trials will need to consider new primary endpoints such as nausea, a complex symptom, where improvement is needed. Economic endpoints should be incorporated to ascertain the cost benefit of antiemetic prophylaxis, taking into account the impact of nausea on work capacity. New antiemetic drugs may be targeted at different receptors, such as opioid, cannabinoid and peptide YY receptors. New research is needed into determining the extent of corticosteroid use. The emetic potential of a range of newer cytotoxics particularly when used in combinations and different scheduling, such as prolonged oral dosing of cytotoxics and use of targeted therapies, are all areas in need of research. More antiemetic studies are needed in niche areas such as in patients receiving high dose chemotherapy, radiation therapy or combined modality therapy. Further evidence of the efficacy of newer antiemetic agents is required in children.

Differential time course of action of 5-HT3 and NK1 receptor antagonists when used with highly and moderately emetogenic chemotherapy (HEC and MEC)

Cisplatin-based highly emetogenic chemotherapy (HEC) displays a biphasic pattern of emesis with both an early and delayed period. In contrast, moderately emetogenic chemotherapy (MEC) has a monophasic pattern. The objective of this analysis was to further investigate the impact of the NK1-receptor antagonist aprepitant on these patterns. Three phase III HEC (patients scheduled to receive cisplatin-based chemotherapy) and one phase III MEC (breast cancer patients scheduled to receive anthracycline plus cyclophosphamide (AC)) trials of aprepitant were included. In all studies, patients were randomized in a 1:1 ratio to an aprepitant regimen (aprepitant plus ondansetron plus dexamethasone) or the standard regimen (ondansetron plus dexamethasone). The exact dosing regimen for ondansetron and dexamethasone was different in each study. In a post hoc analysis, multivariate logistic regression models were used to assess the impact on first emesis at different time intervals after chemotherapy. One thousand five hundred twenty-seven patients and 856 patients were randomized and assessed for efficacy in the HEC and MEC trials, respectively. For HEC, aprepitant reduced the risk of first emesis by 38-77% vs. standard regimen, beginning 15-18 h after cisplatin and extending to 60 h. For MEC, aprepitant reduced the risk of first emesis by 38-61% vs. active control, beginning 3 h after AC and for up to 12 h. Time of onset and duration of enhanced control of emesis with the addition of aprepitant differed between HEC and MEC. This suggests that the pattern of NK1-sensitive mechanisms may vary for different chemotherapy regimens.

Assessing the magnitude of antiemetic benefit with the addition of the NK1 receptor antagonist (NK1) aprepitant for all platinum agents: Analysis of 1,872 patients (pts) in prospective randomized clinical phase III trials (RCTs).

9057 Background: While improvements in the complete control of emesis with NK1s in pts receiving cisplatin (DDP) have been well demonstrated, efficacy reports of this antiemetic class in pts given carboplatin (carbo) or oxaliplatin (oxali) have only been anecdotal. Recent trials documented that emesis with oxali is greater than expected. Guideline groups support using NK1s as part of DDP regimens. Our question relates to the relative magnitude of improvement with aprepitant with newer platinum (PLT) agents in the context of known efficacy with DDP. Methods: We analyzed results of 4 RCTs in 1872 pts receiving chemotherapy. In all trials the control arm on Day 1 was ondansetron (ond) + dexamethasone (dex). The NK1 arms added aprepitant 125 mg on day 1 with 80 mg on days 2 and 3. Control arms for delayed emesis with DDP: dex 8 mg bid in two studies; ond 8 mg bid added in the third; in the aprepitant (investigative) arm only 8 mg of dex daily was given. For delayed emesis with carbo/oxali on the control arm, ...

Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of phase 3 trial of aprepitant in patients receiving adriamycin–cyclophosphamide-based chemotherapy

A number of prognostic factors have been identified as risk factors for chemotherapy-induced emesis. This post-hoc analysis addressed whether: (1) these prognostic factors can identify a low-risk group for whom ondansetron plus dexamethasone alone provide a high level of protection (≥80% no emesis); (2) the NK1 receptor antagonist aprepitant improves antiemetic outcome regardless of emetic risk. Breast cancer patients in a phase III double-blind, placebo-controlled trial were randomized to antiemetic regimens including ondansetron and dexamethasone, or aprepitant, ondansetron, and dexamethasone. Multivariate logistic regression models were used to assess the impact on emesis (but not nausea) of the regimen with aprepitant, and previously reported risk factors, including age (<55 and ≥55 years), ethanol use (0-4 or ≥5 drinks/week), history of pregnancy-related morning sickness, and history of motion sickness, using a modified intent-to-treat approach. Treatment with aprepitant (P < 0.0001), older age (P = 0.006), ethanol use (P = 0.0048), and no history of morning sickness (P = 0.0007) were all significantly associated with reduced likelihood of emesis. The proportion of patients with one, two, or three risk factors who remained emesis free was significantly higher with the aprepitant-containing regimen than with the active control (70.2-82.8% vs. 38.6-66.4%, respectively). Aprepitant markedly improved control of emesis in patients with one or more risk factors. This analysis did not support using risk factors for modifying the antiemetic approach. A low-risk group with zero risk factors for whom aprepitant provided little benefit was of questionable clinical utility, since they comprised less than 3% of patients.

The Importance of Dexamethasone in Reducing Post-Operative Morbidity from a Tonsillectomy

The Importance of Dexamethasone in Reducing Post-Operative Morbidity from a Tonsillectomy

Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review

Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review Albert TucaPalliative Care Hospital Team, Palliative Care Department, Institut Catal&agrave; d&rsquo;Oncologia, L&rsquo;Hospitalet de Llobregat, Barcelona, SpainAbstract: Until now only intravenous and oral formulations of 5HT3 receptor antagonists have been available. Recently a new formulation of a 5HT3 receptor antagonist, transdermal granisetron, has been developed, and approved by the FDA. Three phase I studies to evaluate its pharmacokinetic profile have shown that granisetron administered by a transdermal delivery system is absorbed by passive diffusion and maximal concentration is reached 48 hours after patch application. The patch of 52 cm2, which contains 34.3 mg of granisetron, releases 3.3 mg of the drug every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6 days, similar to levels obtained with 2 mg of oral granisetron, administered every day during the same period of time. Two randomized as yet unpublished clinical trials (phase II/III) have been conducted to evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting, in patients receiving moderately and highly emetogenic chemotherapy, compared with 2 mg of oral granisetron. More than 800 cancer patients were included in the trials. The rate of complete control of acute emesis was 49% for the phase II trial and 60% for the phase III trial. Neither trial showed a statistically significant difference between transdermal and oral granisetron. The control of delayed emesis was observed in 46% of patients, and there were no statistically significant differences between transdermal and oral granisetron. The most common adverse effects in both trials were constipation (&lt;7%) and headache (&lt;1%); there were no statistically significant differences between transdermal and oral granisetron. These data show that transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with both moderate and high emetogenic potential. Efficacy and safety of transdermal granisetron are fully comparable with that of oral granisetron. More clinical trials using regimens of 2 or 3 drugs, including dexamethasone and/or aprepitant, are needed to confirm the place of transdermal granisetron in the control of chemotherapy-induced nausea and vomiting.Keywords: cancer chemotherapy induced nausea and vomiting, selective antagonists of 5HT3 receptors, granisetron, transdemal delivery system