Complete Control Of Emesis Research Articles

Vomiting despite adherence to guidelines: Suboptimal control of vomiting in pediatric cancer patients.

Vomiting is a common and distressing acute side effect of chemotherapy, negatively impacting quality of life, nutritional status, and the ability of patients to tolerate further treatment. Standardized guidelines have been developed to improve control of nausea and vomiting. We aimed to determine the benefit of adherence to clinical practice guidelines (CPGs) on complete control of acute chemotherapy-induced vomiting in newly diagnosed pediatric patients with cancer. An electronic dashboard of pediatric patients newly diagnosed with cancer at Phoenix Children's Hospital between August 2019 and January 2021 and receiving their first cycle of chemotherapy was utilized to monitor chemotherapy regimen, antiemetic medications, and vomiting episodes. Blocks were classified as guideline-inconsistent, guideline-consistent, or guideline-consistent PLUS if additional prophylactic antiemetic medications were utilized. We identified patients with complete control of vomiting, defined as no vomiting and no additional antiemetics needed. Among 136 patients, 29% received guideline-inconsistent care, 37% received guideline-consistent care, and 34% received guideline-consistent PLUS care. Overall, 48% of patients achieved complete control of vomiting. Older patients (p<0.0001) and those receiving higher emetogenicity chemotherapy (p=0.0003) were more likely to receive guideline-consistent or guideline-consistent PLUS therapy. With guideline-consistent and -consistent PLUS grouped together, the diagnosis was also associated with improved adherence to CPGs (p=0.022). Multivariate analysis showed that patients more likely to receive guideline-consistent prophylaxis were of older age (OR 1.11, p=0.016) and solid tumor patients (OR 5.59, p=0.028). Despite high rates of CPG adherence, complete control of vomiting remains suboptimal, which highlights the need for novel and/or risk-adapted therapies.

Evaluation of the Use of Fosaprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Pediatric Patients.

A neurokinin-1 (NK1) receptor antagonist is recommended with a 5-HT3 receptor antagonist and dexamethasone for prevention of chemotherapy-induced nausea and vomiting (CINV) in adult patients receiving highly emetogenic chemotherapy. Data for fosaprepitant use in pediatric patients is lacking. A retrospective chart review was conducted using an electronic medical record to characterize the use of fosaprepitant in patients aged 10 months to 18 years at a single institution from August 2015 to January 2017. Thirty-nine patients received fosaprepitant 4 mg/kg (maximum, 150 mg) for prevention of CINV, and 35 were included in the analysis. Ten patients 5 years of age or older who received fosaprepitant after October 2016 were eligible for a follow-up phone call to assess control of delayed CINV. Complete control of emesis was observed in 89% of patients during the acute phase, 63% during the delayed phase, and 60% overall. Overall incidence of nausea as documented in the medical record was 43%. Among the 10 patients who completed follow-up phone calls, 30% experienced emesis and 50% experienced nausea after discharge. Fosaprepitant may be safe and effective in the prevention of CINV in pediatric patients as young as 10 months of age.

Influence of pharmaceutical care on the delayed emesis associated with chemotherapy

Complete control of emesis during chemotherapy remains to be achieved. This could be improved by increasing adherence to medicines and recommendations. The aim of this study was to analyse the effects of pharmaceutical care on the incidence of delayed chemotherapy-induced nausea and vomiting (CINV) in adult cancer outpatients. This is a longitudinal prospective intervention study. Patients included were those who received a new cancer intravenous treatment. We compared complete response (no vomiting and no rescue treatment) and the incidence of nausea in the control group (CG) and in the intervention group (IG), as well as patients' adherence. Pharmaceutical intervention consisted of: reviewing the antiemetic protocol and giving some recommendations to the patients. 102 patients were studied. In the delayed phase complete response was achieved in 84.8 % of the patients in the IG, compared with 69.6 % in the control group [absolute risk reduction (ARR), 15.2 %; p = 0.144]. Regarding absence of vomiting, the difference was higher (71.0 CG vs 97.0 % IG, ARR, 26.0%; p = 0.002). Absence of delayed nausea were also better in the IG (61 vs. 52 %). Compliant patients increased from 59 to 76 %. The intervention of a pharmacist reduced the incidence of delayed CINV and improved medication adherence.

Cyclophosphamide causes activation of protein kinase A (PKA) in the brainstem of vomiting least shrews (Cryptotis parva)

Complete control of emesis caused by cyclophosphamide (CPA) is of immense interest to both patients and physicians. Serotonin 5-HT3- and tachykinin NK1-receptor antagonists are widely used antiemetics in clinic, but they fail to completely control CPA-induced emesis. New antiemetic targets for the full control of CPA-induced vomiting are lacking. We therefore examined the effects of CPA on emetic targets downstream of 5-HT3- and NK1- receptors in an attempt to better understand the molecular bases of CPA-induced emesis. Acute CPA (200mg/kg, i.p.) administration in the least shrew caused a biphasic pattern of emesis over a 40h observation period, with maximal peak vomit frequency during the 1st hour of treatment (acute phase), followed by a delayed-phase which peaks at 27th hour. The NK1 receptor mRNA levels increased significantly at 8h post-CPA treatment in the brainstem, and at 28h in the whole intestine. Substance P mRNA levels tended to increase both in the brainstem and intestine at most time-points post-CPA injection, however due to large variability, they failed to attain significance. Likewise, protein expression profiles of both NK1- and 5-HT3 -receptors in the brainstem were unchanged at any time-point. However, phosphorylation levels of protein kinase A (PKA), but not of extracellular signal-regulated protein kinase 1/2 (ERK1/2), were increased at 2, 8, 22, 28, and 33h time-points after the treatment with CPA. Moreover, brainstem but not frontal cortex cAMP tissue levels tended to be elevated at most time-points, but significant increases occurred only at 1 and 2h post-CPA treatment. The phosphodiesterase inhibitor, rolipram, caused significant increases in shrew brainstem cAMP levels which were associated with its capacity to produce vomiting, while pretreatment with SQ22536, an inhibitor of adenylyl cyclase, prevented rolipram-induced emesis. The results demonstrate that accumulation of cAMP and subsequent activation of PKA in the brainstem may help to initiate and sustain emesis induced by CPA in the least shrew. Our findings suggest that suppression of the cAMP/PKA cascade may have antiemetic potential in the management of CPA-induced emesis.

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, ...

Management of platinum-based chemotherapy-induced acute nausea and vomiting: is there a superior serotonin receptor antagonist?

The last decade has witnessed the great impact of 5-hydroxytryptamine-3 receptor (5-HT(3))antagonists in revolutionizing the management of platinum-based chemotherapy-induced acute nausea and vomiting (CINV). However, despite the availability of a variety of 5-HT(3) antagonists, little data is published to support superiority of one drug over another, leaving the choice of serotonin receptor antagonist largely empirical. The National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines for management of chemotherapy-associated nausea and vomiting cleary endorse the use of serotonin receptor antagonist; however, no single agent is preferred over the rest. Data for patients (n=159) receiving platinum-based chemotherapy regimens were retrospectively collected . Patients getting 5-HT(3) antagonists without steriods or those with known history of brain metastasis, gastroparesis, and intestinal obstruction were not eligible for the study. Patient characteristics including age, gender, primary diagnosis, history of heavy alcohol intake, chemotherapy regimen administered , number of cycles, and Eastern Cooperative Group performance status at the start of therapy were noted. Primary outcome was the complete control of platinum-induced acute nausea and vomiting. Secondary outcome measures included control of > or = grade 1 nausea or vomiting, comparison of two doses of dexamethasone, and antiemetic eficacy among various platinum drugs. National Cancer Institute Common Toxicity Criteria version 2.0 was used to assess toxicity. A total of 126 patients received 369 cycles of platinum-based therapy. Dolasetron ( n=157), granisetron ( n=81), and ondansetron ( n=131) achieved complete control of vomiting in 89.8, 95.5, and 92.3% (p=0.67) of cycles, respectively. Respectively, complete nausea control was observed in 68.1, 75.3 and, 69.4% (p=0.50). Dexamethasone 20 mg was not superior to 10 mg in complete control of nausea and vomiting ( p= 0.15 and p=0.63, respectively). However, complete nausea control was signinficantly better in the subgroup of patients getting cisplatin-compared with carboplatin-based regimens (78.8% vs. 67.7%, p<0.05). No significant difference exists in the antiemetic efficacy of the three 5-HT(3) antagonists studied in controlling CINV when administered in combination with dexamethasone. Choicce of antiemetic regimen should therefore be based on drug cost.

5-Hydroxytryptamine-3 Receptor Antagonist With or Without Short-Course Dexamethasone in the Prophylaxis of Radiation Induced Emesis: A Placebo-Controlled Randomized Trial of the National Cancer Institute of Canada Clinical Trials Group (SC19)

To evaluate the effectiveness of prophylactic dexamethasone for the control of radiation induced emesis (RIE) when added to ondansetron during days 1 to 5 of fractionated radiotherapy. The study had two hypotheses: ondansetron and dexamethasone could provide superior control of RIE over ondansetron alone during the prophylactic period and; the combination could provide sustained control of RIE during subsequent fractions of radiotherapy. Between May 2001 to Jan 2004, 211 patients receiving radiotherapy (> or = 15 fractions) to the upper abdomen were randomly assigned to receive ondansetron 8 mg bid with either dexamethasone 4 mg daily or placebo during fractions 1 to 5. Rescue antiemetics were provided. During the prophylactic period there was a trend for improved complete control of nausea in the dexamethasone arm (50% v 38%; P = .06) while complete and partial control of emesis, average nausea score, and use of rescue medications were similar in the two groups. During the overall study period patients receiving dexamethasone had better complete control of emesis (23% v 12%; P = .02) and a lower average nausea score (0.28 v 0.39; P = .03); there was a trend towards less use of rescue medications with dexamethasone (70% v 80%; P = .09); other outcomes were similar on the two arms. Quality of life analysis showed a significant difference in appetite. The addition of dexamethasone to ondansetron as prophylaxis provides a modest improvement in protection against RIE during moderately emetogenic fractionated radiotherapy. It is a potentially useful addition to 5-hydroxytryptamine-3 receptor antagonists in this setting.

Relative efficacy of various 5- hydroxytryptamine receptor antagonists in the prevention and control of acute nausea and vomiting associated with platinum-based chemotherapy

8623 Background: The introduction of 5-Hydroxytryptamine-3 receptor (5-HT3) antagonists has represented a significant clinical advance in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV), particularly for patients receiving highly emetogenic platinum-based regimens. However no study to date has compared the relative efficacy of Dolasetron, Granisetron, Ondansetron and Palonosetron with Dexamethasone in the prevention and control of acute CINV in patients undergoing platinum-based therapy. Methods: Retrospective data were reviewed for 207 consecutive patients receiving Platinum-based chemotherapy in our infusion center between November 1999 and August 2005. Patients receiving 5-HT3 antagonists without Dexamethasone (n=11) were not eligible for the study. Further 15 patients were excluded because of no documentation of CINV. The remaining 181 patients constitute the subject of this study. Patient characteristics including age, sex, race, diagnosis, history of heavy alcohol intake, chemotherapy regimen administered, number of cycles, and performance status at the start of therapy were noted. Primary outcome measure was complete control of acute CINV. National Cancer Institute Common Toxicity Criteria version 2.0 was used to assess toxicity. Results: The 181 patients received 572 cycles of platinum-based therapy. Dolasetron (n=157), Granisetron (n=81), Ondansetron (n=131) and Palonosetron (n=203) (each given with Dexamethasone) achieved complete control of vomiting in 89.8%, 95.5%, 92.3% and 88.1% (ρ=0.86) of cycles respectively. Respectively, complete nausea control was observed in 68.1%, 75.3%, 69.4% and 73.3% (ρ=0.35). DEX 20 mg was not superior to 10mg in complete control of nausea and vomiting (ρ=0.06 and ρ=0.67 respectively). Similarly complete control of nausea and vomiting (ρ=0.12 and ρ=0.10 respectively) was not significantly different in patients getting cisplatin compared to carboplatin based regimens. Conclusion: This study does not demonstrate a significant difference in the efficacy of the four 5-HT3 antagonists in controlling acute CINV. The higher dose of Dexamethasone confers no added benefit over the lower 10mg dose. No significant financial relationships to disclose.

Effectiveness of serotonin-receptor antagonist antiemetic therapy over successive courses of carboplatin-based chemotherapy.

There are extremely limited data available in the general oncology or gynecologic cancer literature to document the effectiveness of antiemetic therapy over multiple courses of cytotoxic chemotherapy. To examine this highly clinically relevant issue, we analyzed the complete treatment course of patients with gynecologic cancers receiving carboplatin-based chemotherapy regimens who had participated in one of four institutional serotonin-receptor antagonist antiemetic trials, which had specifically evaluated the benefits of such therapy during only the first treatment course. Medical records were reviewed to examine the development of emesis during subsequent chemotherapy treatment cycles. The 91 patients included in this analysis received a median of 6 courses (range 1-18) of carboplatin (initial AUC dose 4, 5, and 6 in 29, 29, and 32 patients, respectively). All received ondansetron or granisetron plus dexamethasone with every treatment course. Complete control of emesis (no acute or delayed nausea or vomiting) was experienced by 56 (62%) patients during every cycle. Conversely, 20% of women noted one or more episodes of nausea without vomiting and 19% developed at least one incidence of vomiting. In no case was emesis considered to be severe (grade 3), and no patient required either discontinuation of carboplatin or a dose reduction due to the development of emesis. In the large majority of patients, serotonin-receptor antagonist antiemetic therapy, administered in combination with dexamethasone, is highly effective over multiple courses in preventing significant carboplatin-induced nausea and vomiting.

Antiemetic Efficacy of Granisetron: a Randomized Crossover Study in Patients Receiving Cisplatin-containing Intraarterial Chemotherapy

Cisplatin (CDDP) is one of the most active chemotherapeutic agents but is among the most emetogenic drugs. The emetic side-effects of CDDP-containing intraarterial chemotherapy have not been evaluated in a prospective randomized trial and the efficacy of serotonin antagonists in preventing the emesis associated with this method of CDDP administration has not been assessed. CDDP 50 mg/m2 and methotrexate 30 mg/m2 were administered every 3 weeks through intraarterial catheters placed in the bilateral internal iliac arteries. Patients were classified into two groups: granisetron treatment group (group G) and no treatment group (group NG) with the first course of chemotherapy, crossing over with the second course. The patients in group G received granisetron 40 micrograms/kg by intravenous infusion. Although intraarterial CDDP administration produced less emesis than intravenous CDDP administration, at the same concentration, gastrointestinal toxicity is still the most unpleasant side-effect for patients. Granisetron administration significantly reduced nausea and vomiting during the acute emetic phase (an evaluation of treatment as very effective and effective was made in 89% in group G and 33% in group NG (P < 0.001). Complete control of emesis was achieved in 68 and 18% of patients in groups G and NG, respectively (P < 0.0001). A single prophylactic infusion of granisetron was effective in preventing the nausea and vomiting associated with intraarterial CDDP-containing therapy.

S7-5 - Non-peptide tachykinin NK1 antagonists: Towards complete control of emesis

S7-5 - Non-peptide tachykinin NK1 antagonists: Towards complete control of emesis

Dose-ranging evaluation of the antiemetic efficacy of intravenous dolasetron in patients receiving chemotherapy with doxorubicin or cyclophosphamide

Selective 5-HT3 antagonists have proven to be safe and effective for the prevention of chemotherapy-induced nausea and vomiting. Dolasetron is a new highly selective addition to this class of antiemetics that has been shown to have significant antiemetic activity in patients receiving cisplatin-containing regimens. This pilot study was designed to evaluate the antiemetic efficacy of dolasetron in cancer patients receiving doxorubicin and/or cyclophosphamide. This study used an open-label, non-randomized design to evaluate the efficacy and safety of intravenous dolasetron in the prevention of emesis in patients receiving doxorubicin (25-75 mg/m2) and/or cyclophosphamide (400-1200 mg/m2). Sixty-nine patients received a single, intravenous dose of dolasetron over 15-20 min beginning 30 min prior to the start of chemotherapy. Dose levels of dolasetron studied were: 0.3, 0.6, 1.2, 1.8 and 2.4 mg/kg. Patients were monitored for emesis, nausea and adverse events for 24h after the start of chemotherapy. Overall, 61% of patients experienced complete control of emesis. No significant trend towards increased antiemetic efficacy (P = 0.076) or nausea control with increasing dolasetron dose was noted, although the power to detect significant differences was limited by the small number of patients on the 0.3-mg/kg and 2.4-mg/kg dose levels. Age, gender, and type of chemotherapy were significant predictors of complete antiemetic control. Adverse events were generally mild and included headache, chills, lightheadedness, fever, diarrhea, dizziness, and asymptomatic prolongation of ECG intervals. Intravenous dolasetron is safe and effective in the prevention of emesis induced by doxorubicin and/or cyclophosphamide.

Omitting nitrous oxide in general anaesthesia: meta-analysis of intraoperative awareness and postoperative emesis in randomized controlled trials

We have reviewed randomized controlled trials to assess the effectiveness and safety of anaesthetics which omitted nitrous oxide (N2O) to prevent postoperative nausea and vomiting (PONV). Early and late PONV (6 and 48 h after operation, respectively), and adverse effects were evaluated using the numbers-needed-to-treat (NNT) method. In 24 reports with information on 2478 patients, the mean incidence of early and late vomiting with N2O (control) was 17% and 30%, respectively. Omitting N2O significantly reduced vomiting compared with a N2O regimen; the combined NNT to prevent both early and late vomiting with a N2O-free regimen was about 13 (95% confidence intervals (CI) 9, 30). The magnitude of the effect depended on the incidence of vomiting in controls. In studies with a baseline risk higher than the mean of all reports, the NNT to prevent both early and late vomiting with a N2O-free anaesthetic was 5 (95% CI 4, 10). When the baseline risk was lower than the mean, omitting N2O did not improve outcome. Omitting N2O had no effect on complete control of emesis or nausea. The NNT for intraoperative awareness with a N2O-free anaesthetic was 46 compared with anaesthetics where N2O was used. This clinically important risk of major harm reduces the usefulness of omitting N2O to prevent postoperative emesis.

158 Ondansetron antiemetic prophylaxis in patients undergoing fractionated radiotherapy

Patients (n = 109) given fractionated radiotherapy of the abdomen were studied to compare the antiemetic efficacy of ondansetron (ond) with placebo. The patients recorded daily emesis, nausea and bowel habit and graded weekly symptoms of nausea, vomiting, diarrhea and lack of appetite. The EORTC C30 questionnaire was completed. Sixty-seven percent of patients given ond had complete control of emesis compared with 45% of patients with placebo ( P P P P

Granisetron. An update of its therapeutic use in nausea and vomiting induced by antineoplastic therapy.

Granisetron is a selective serotonin3 (5-hydroxytryptamine3, 5-HT3) receptor antagonist which has significant antiemetic activity against chemotherapy-induced nausea and vomiting. A single prophylactic intravenous dose is sufficient to control acute nausea and vomiting in approximately 60 to 70% of patients. In comparative studies, the acute antiemetic efficacy of granisetron is equivalent or superior to that of traditional antiemetic regimens even in patients receiving highly emetogenic cisplatin-containing chemotherapy. However, limited data have suggested that granisetron therapy offers no advantages over traditional antiemetics in terms of the control of delayed emesis. Recently, a number of large randomised studies have directly compared the efficacy and tolerability of granisetron, ondansetron and tropisetron and reported no significant differences between the 3 drugs in controlling acute nausea and vomiting, although 1 study reported a modest statistical advantage for granisetron over ondansetron but not tropisetron in the complete control of vomiting. In crossover studies, significantly more patients preferred granisetron to either ondansetron or tropisetron. The efficacy of granisetron appears to be maintained with repeated doses over several cycles of chemotherapy, although the influence of various prognostic factors affecting antiemetic response has not been adequately analysed. Concomitant administration of dexamethasone significantly improves the acute antiemetic efficacy of granisetron, increasing response rates by approximately 15%. Granisetron is an effective antiemetic in children undergoing highly emetogenic chemotherapy, and effectively controls radiotherapy-induced and postoperative nausea and vomiting. Trials using an oral formulation are scarce at present, but preliminary results suggest a similar efficacy and tolerability profile to that of the intravenous formulation. Granisetron has been well tolerated in clinical trials. The most frequently reported adverse event has been headache (14%). Extrapyramidal effects, which can limit the use of traditional antiemetics such as metoclopramide, have not been reported with granisetron. Thus, recent data confirm that granisetron is an effective and well tolerated agent for the prophylactic treatment of chemotherapy-induced acute nausea and vomiting, with efficacy equivalent or superior to that of other currently available agents. It has a promising role to play in paediatric oncology, and is an effective agent in controlling radiotherapy-induced acute emesis. Granisetron offers comparable or superior efficacy in controlling acute nausea and vomiting with a much simpler dosage regimen than that of traditional antiemetic regimens.

A randomised cross-over trial of antiemetic therapy for platinum-based chemotherapy. Improved control with an intensive multiagent regimen

In a partially blinded randomised cross-over trial, 78 patients receiving cisplatinum based chemotherapy were assigned to receive two forms of antiemetic therapy: SAD, a regimen composed of serenace (haloperidol), ativan (lorazepam), and dexamethasone followed by low dose maxolon (metoclopramide) and STADMAX, a regimen composed of scopolamine (hyoscine), tavegyl (clemastine), ativan, dexamethasone and high dose maxolon. Each antiemetic regimen was given in random order, with the first and second cycles of cytotoxic chemotherapy. 66 (85%) patients completed both cycles of antiemetic therapy and were available for the cross-over comparison. Significantly less acute vomiting, as assessed by nurse observer ( P < 0.0001), and less delayed vomiting, as assessed by patient diary ( P = 0.03), were seen with STADMAX. In the first 18 h, complete control of vomiting (no episodes) was achieved in 30 (45%) patients with STADMAX compared with 10 (15%) receiving SAD. Overall, major control of emesis (⩽ 2 episodes) was achieved in 56 (85%) patients with STADMAX compared with 35 (53%) receiving SAD. Vomiting was also better controlled on STADMAX in the week after this initial 18 hour period based on the 7 day patient diary with no vomiting episodes in 18 65 (28%) on STADMAX vs. 13 65 (20%) on SAD. However, no significant differences in appetite, nausea or vomiting were found when based on linear analogue self assessment (LASA) scales recorded by patients. Significant differences in side effects of the two antiemetic regimens were noted on LASA scales with more dry mouth ( P = 0.01), blurred vision ( P = 0.03) and diarrhoea ( P = 0.04) associated with STADMAX and more restlessness ( P = 0.002) associated with SAD. Significantly, no episodes of dystonic reactions were seen among patients on either regimen. In the 68 patients who completed both cycles and were in a position to express a preference, 46 (68%) preferred STADMAX compared with only 20 (29%) who preferred SAD ( P = 0.001), while 2 patients expressed no preference. It is concluded that STADMAX is the preferred regimen to SAD for the control of cisplatinum-related emesis. It has a role, both where specific serotonin 3 antagonists are not available and as a model for building more effective combinations where these agents are available.

ONDANSETRON VERSUS METOCLOPRAMIDE IN THE PREVENTION OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING - A METAANALYSIS

Nausea and vomiting remain important clinical problems occuring in 25 to 50% of patients receiving chemotherapy for cancer. Clinical trials comparing a new antiemetic drug, ondansetron, to metoclopramide have suggested improved control of nausea and vomiting but studies disagree on the magnitude of the treatment effect and its statistical significance. We combined evidence from randomized controlled trials in a meta-analysis of the efficacy and safety of ondansetron compared to metoclopramide in the prevention of acute (less-than-or-equal-to 24 hours) nausea and emesis associated with chemotherapy. Literature search identified six randomised controlled trials of ondansetron versus metoclopramide in an adult population. Study outcomes were the observed incidence of emesis (vomiting or retching) and patient-reponed grades of nausea after chemotherapy. For meta-analysis of each outcome we defined therapeutic success as complete protection (ie. zero episodes during 24 hours following chemotherapy). The relative odds of success (ondansetron/metoclopramide) was calculated for each trial and all trials combined. Results were expressed as a relative risk (RR) for zero emesis or nausea at 24 hours. The six trials reported on 705 patients (median age range 53-59 years; 57% female). Relative odds for complete control of emesis was greater than one in all trials but was nonsignificant (p>0.05) in two trials, including the largest trial. When trials were combined, summary odds ratios for control of emesis and nausea were greater than one (p<0.05). RR of zero emesis with ondansetron was 1.72 (95% CI 1.45 to 1.97) and was similar for nausea (RR= 1.78, 95% CI 1.39 to 2.13). In trials using high-dose cisplatin chemotherapy, higher rates of extrapyramidal affects and diarrhea were associated with metoclopramide (p<0.05) while headache was frequently associated with ondansetron (p<0.05). Combined clinical trial evidence supports the conclusion. that, relative to metoclopramide, ondansetron places patients at a much lower risk of nausea and emesis following chemotherapy with moderately or highly emetogenic regimens.

Parenteral ondansetron for the treatment of chemotherapy- and radiation-induced nausea and vomiting.

Ondansetron hydrochloride dihydrate is a 5-hydroxytryptamine (5-HT3) antagonist that was recently approved by the Food and Drug Administration for the treatment of chemotherapy-induced emesis. The mechanism of action is thought to be due to competitive inhibition of specific serotonin receptors in the central nervous system and gastrointestinal tract. In clinical trials with cisplatin-induced emesis, ondansetron resulted in complete control of vomiting (0-2 episodes) in 55-87% of patients during the first 24 hours of chemotherapy administration. It was significantly more effective than metoclopramide in comparative trials. Ondansetron is also being investigated for the treatment of radiation- and anesthesia-associated nausea and vomiting. Studies in animals demonstrate potential efficacy in the treatment of anxiety, drug withdrawal, and schizophrenia. The drug is generally well tolerated, with no reported extrapyramidal reactions.

Oral ondansetron (GR 38032F) for the control of CMF-induced emesis in the outpatient

The efficacy of the serotonin antagonist ondansetron (GR 38032F) was evaluated in the prevention of nausea and vomiting induced by CMF chemotherapy in 29 breast cancer patients. At their first treatment course of CMF, all given IV on day 1 q 21 days, patients were given oral antiemetic treatment as follows: ondansetron 8 mg, 2 h prior to CMF, repeated after 5 and 10 h the day of chemotherapy and then 8 mg tds for a minimum of 3 days to a maximum of 5 days following chemotherapy. At first course of CMF, complete protection from emesis and nausea was observed in 86.2% and 62% of patients, respectively. At subsequent CMF courses with ondansetron, complete control of emesis was observed in 80% of patients. Side effects were mild and no dystonic reactions were observed. Ondansetron represents an effective, safe, and easily administered outpatient regimen. The addition of a corticosteroid to ondansetron could further improve control of CMF-induced emesis.

Tetracosactrin vs. methylprednisolone in the prevention of emesis in patients receiving FEC regimen for breast cancer

0.5 mg tetracosactrin is considered to be equivalent to 40 mg methylprednisolone with regard to the induced cortisol secretion. 97 female breast cancer patients who received their first two FEC courses (epirubicin 50–75 mg/m 2, 5-fluorouracil 500 mg/m 2, cyclophosphamide 500 mg/m 2) entered this randomised crossover study (76 had previously received an adjuvant treatment); tetracosactrin was administered intramuscularly and methylprednisolone intravenously immediately before chemotherapy administration. The tolerability was evaluated using a diary card during 5 days and patients were asked for their preference at the end of the two cycles. There was no difference either for vomiting (dry heaves were included) or nausea between the two treatments (the analysis was performed on day 1, the worse day of days 2 and 3 and the worse day of days 4 and 5). At day 1, 49% of the patients experienced no or mild nausea after tetracosactrin and 62% after methylprednisolone (not significant) (first period analysis); a complete control of vomiting (including dry heaves) was observed in 49% of the patients after tetracosactrin and 53% after methylprednisolone (not significant). No difference was observed between patients with or without previous chemotherapy. However, slightly more patients preferred tetracosactrin ( P = 0.048).