Prophylactic Antiemetic Regimens Research Articles

Antiemetic Prophylaxis for Postdischarge Nausea and Vomiting and Impact on Functional Quality of Living During Recovery in Patients with High Emetic Risks: A Prospective, Randomized, Double-Blind Comparison of Two Prophylactic Antiemetic Regimens

We compared two antiemetic prophylaxis regimens, their efficacy for preventing postdischarge nausea and vomiting, and their impact on quality of living, during recovery. Sixty-four women undergoing outpatient gynecological surgery and at high risk for emesis were randomized into one of two groups. The study group received intraoperative IV dexamethasone 8 mg and ondansetron 4 mg, followed with an 8 mg oral disintegrating ondansetron tablet, to be taken on discharge and in the morning of postoperative days 1 and 2. The control group received only the IV ondansetron 4 mg intraoperatively. The incidence and severity of emetic symptoms and pain were assessed while patients were in the recovery room and via telephone and patient diary for 5 days after discharge. A modified functional living index of emesis was used to assess the impact on quality of living during recovery. Sixty patients, 30 in each group, completed the study. The incidences for postdischarge nausea were 57% and 20%, and for postdischarge vomiting 20% and 3% in the control and study groups, respectively, for the period between the 8th and 120th hours postanesthesia (P < 0.05). Thirty-three percent of the study and 60% of the control group reported that emetic symptoms negatively affected their quality of living (P < 0.05). When compared with a single dose of intraoperative IV ondansetron prophylaxis, our study regimen of additional intraoperative dexamethasone and once a day ondansetron significantly reduced the incidence of postdischarge nausea and vomiting and its negative impact on quality of living during the first 5 days of recovery.

Prevention of chemotherapy-induced nausea and vomiting: focus on fosaprepitant

Fosaprepitant is a prodrug of aprepitant, a neurokinin(1) (NK(1)) receptor antagonist used in prophylactic antiemetic regimens used prior to cytotoxic chemotherapy. Fosaprepitant is being developed to provide a parenterally administered alternative to the orally administered aprepitant. Fosaprepitant is rapidly converted to aprepitant and an intravenous dose of 115 mg is bioequivalent to 125 mg orally, with similar plasma concentrations at 24 hours. In phase I and II trials fosaprepitant shows efficacy, but the large randomized efficacy studies have utilized aprepitant. When it is added to dexamethasone and a 5HT(3) receptor antagonist on day 1 prior to chemotherapy aprepitant improves the control of acute post chemotherapy emesis and when continued on days 2 and 3 with dexamethasone it demonstrated even greater improvement in the control of delayed emesis. This has been shown with both cisplatin-containing regimens and those based upon cyclophosphamide and an anthracycline. Fosaprepitant is well tolerated with mild to moderate venous irritation being the only additional toxicity to those seen with oral aprepitant, and that is a function of dose, concentration, and infusion rate. Headaches are the other toxicity most commonly reported. Fosaprepitant can be used as a parenteral alternative to aprepitant in regimens to control chemotherapy-induced emesis.

Prevention of nausea and vomiting following breast surgery

Background The purpose of this study was to determine the rate of nausea and vomiting in women following breast surgery (PONV) under general anesthesia (GA), before and after the introduction of a standardized prophylactic anti-emetic (AE) regimen. Methods We performed a retrospective review of eligible patients, between July 2001 and March 2003. Patients operated on before September 2002 had standard preoperative care (old cohort [OC]); patients operated on after September 2002 were treated prophylactically with oral dronabinol 5 mg and rectal prochlorperazine 25 mg (new cohort [NC]). Data were collected from hospital records regarding age, diagnosis, comorbid conditions, previous anesthesia history, anesthesia and operative details, episodes PONV, and use of AE. The rate and severity of PONV was calculated for both cohorts. Results Two hundred forty-two patients were studied: 127 patients in the OC and 115 patients in the NC. The median age was 56 years (range 32 to 65). The rate of nausea and vomiting were significantly better in the patients treated prophylactically with dronabinol and prochlorperazine (59% vs. 15%, P < .0001 and 29% vs. 3%, P < .0001). Twenty patients in the OC were given some prophylactic AE treatment and 12 (60%) of them required further treatment; only 12 of 109 patients (11%) in the NC required further AE treatment ( P < .0001). Conclusion PONV is a significant problem in breast surgical patients. Preoperative treatment with dronabinol and prochlorperazine significantly reduced the number and severity of episodes of PONV.

Comparison of Prophylactic Antiemetic Therapy with Patient-controlled Epidural Analgesia after Thoracotomy

Background: Patient controlled analgesia (PCA) has become an important means for treating postoperative pain. However, postoperative nausea and vomiting (PONV) are a major problem for patient using PCA system. This study was designed to evaluate the efficacy of two prophylactic antiemetic regimens on PONV during PCA after lobectomy. Methods: Sixty five patients, who underwent lobectomy and received a mixture of 0.18% ropivacaine at 0.5/kg/hr of fentanyl (2,000) via thoracic epidural catheter. The study design was a prospective, randomized, double-blinded, placebo-controlled study. Group C was saline control group. In Group A or B, (ramosetron) or (ondansetron) was administered as an intravenous bolus at completion of operation. We assessed the frequency and severity of PONV at 6, 24, 48 hours after anesthesia. Postoperative pain was assessed 6 hr after the operation and everyday for 6 days on visual analog scale (VAS). Postoperative side effects and patient satisfaction for epidural analgesia were assessed by 4 grades. Results: PONV occurred in 20%, 20%, and 35% of patients in Group A, B, and C at 6 hr after anesthesia, and 12%, 30%, and 30% at 24 hr after anesthesia. There were no significantly statistical differences among three groups. The VAS scores during coughing were higher than those of resting state without intergroup difference. There were no serious clinical adverse events caused by the study drug and epidurally administered drugs in any study groups. Conclusions: This study found that ramosetron and ondansetron for preventing PONV during epidural PCA after lobectomy was not different from placebo control.

The Antiemetic Efficacy of Oral Ondansetron plus Intravenous Dexamethasone in Patients with Gynecologic Malignancies Receiving Carboplatin-Based Chemotherapy

Purpose. The purpose of this study was to develop a cost-effective prophylactic antiemetic regimen for the prevention of carboplatin-induced emesis.Methods. Patients being treated in the Gynecologic Cancer Program of the Cleveland Clinic Taussig Cancer Center with a carboplatin-based chemotherapy regimen received a prophylactic antiemetic program consisting of a single dose of oral ondansetron (16 mg) plus intravenous dexamethasone (20 mg) approximately 30 min prior to chemotherapy. Evaluation of the effectiveness of this antiemetic regimen was performed during a single treatment course.Results. A total of 27 patients (median age, 62; range, 41–83) participated in this phase 2 trial. Three patients received single-agent carboplatin, and 24 were treated with either a carboplatin/paclitaxel or carboplatin/docetaxel regimen. The carboplatin AUC dosing level was 4, 5, or 6 in 6, 5, and 16 individuals, respectively. No patient developed vomiting; 2 (7%) individuals experienced nausea during the 24-h period following chemotherapy administration.Conclusion. The combination of a single dose of oral ondansetron (16 mg) plus intravenous dexamethasone (20 mg) is an effective prophylactic antiemetic regimen for patients receiving carboplatin-based chemotherapy.

Low-Dose Oral Granisetron (1 mg) plus Intravenous Dexamethasone: Efficacy in Gynecologic Cancer Patients Receiving Carboplatin-Based Chemotherapy

Objective.The objective of this study was to determine the efficacy of a low-dose oral granisetron plus intravenous dexamethasone prophylactic antiemetic regimen in patients receiving carboplatin-based chemotherapy.Patients and methods.Patients with gynecologic malignancies being treated with either single-agent carboplatin or a carboplatin–paclitaxel regimen received a single 1-mg oral dose of granisetron 30 min prior to chemotherapy plus intravenous dexamethasone (20 mg) as prophylaxis for emesis. Patients either had not previously been treated with chemotherapy or had not received any cytotoxic drugs for ≥4 months prior to study entry. Effectiveness was evaluated based on the degree of control of nausea and vomiting during the 24 h following treatment.Results.Of the 32 patients participating in this phase 2 trial, only 2 (6%) experienced any degree of nausea or vomiting within the first 24 h of chemotherapy administration. Both of these individuals had carcinomatosis and were experiencing emesis prior to chemotherapy. One patient developed mild delayed nausea >24 h after treatment. No major or minor toxic effects of the antiemetic regimen observed.Conculsion.A 1-mg dose of oral granisetron plus intravenous dexamethasone (20 mg) is a safe, effective, and relatively inexpensive prophylactic antiemetic regimen for patients receiving single-agent carboplatin or combination carboplatin–paclitaxel chemotherapy.

485 Incidence of emesis and nausea in fractionated radiotherapy patients

The findings of a large, multicentre assessment involving 1387 patients undergoing fractionated radiotherapy, between thorax and pelvis, demonstrated that few patients receive anti-emetic prophylaxis (≈15%). A subgroup of patients (n = 297) consented to complete the patient specific assessments recording daily their emesis and nausea; 269 patients (Group I) who had received no anti-emetic prophylaxis (normal emetogenic risk) and 28 patients (Group II) who had received prophylactic anti-emetic regimens not containing a 5-HT3 receptor antagonist (elevated emetogenic risk). In Group I, 38% of patients experienced moderate/severe nausea, and 36% experienced emesis with 47% of patients experiencing both symptoms. Despite anti-emetic prophylaxis, 61% of patients in Group II experienced moderate/severe nausea and 57% experienced emesis with 75% of patients experiencing both symptoms. Twenty four percent of patients who completed the assessment received anti-emetic medication as treatment/rescue on at least one day of their course of fractionated radiotherapy. As expected the higher the dose per fraction of radiotherapy, the earlier in the course of radiotherapy patients received treatment/rescue anti-emetic medication. This assessment confirmed that the majority of patients receiving fractionated radiotherapy do not receive anti-emetic prophylaxis, although a significant proportion of patients experience emesis and nausea. In addition there is a need for more effective anti-emetic prophylaxis. The findings of a large, multicentre assessment involving 1387 patients undergoing fractionated radiotherapy, between thorax and pelvis, demonstrated that few patients receive anti-emetic prophylaxis (≈15%). A subgroup of patients (n = 297) consented to complete the patient specific assessments recording daily their emesis and nausea; 269 patients (Group I) who had received no anti-emetic prophylaxis (normal emetogenic risk) and 28 patients (Group II) who had received prophylactic anti-emetic regimens not containing a 5-HT3 receptor antagonist (elevated emetogenic risk). In Group I, 38% of patients experienced moderate/severe nausea, and 36% experienced emesis with 47% of patients experiencing both symptoms. Despite anti-emetic prophylaxis, 61% of patients in Group II experienced moderate/severe nausea and 57% experienced emesis with 75% of patients experiencing both symptoms. Twenty four percent of patients who completed the assessment received anti-emetic medication as treatment/rescue on at least one day of their course of fractionated radiotherapy. As expected the higher the dose per fraction of radiotherapy, the earlier in the course of radiotherapy patients received treatment/rescue anti-emetic medication. This assessment confirmed that the majority of patients receiving fractionated radiotherapy do not receive anti-emetic prophylaxis, although a significant proportion of patients experience emesis and nausea. In addition there is a need for more effective anti-emetic prophylaxis.

Adjuvant propofol enables better control of nausea and emesis secondary to chemotherapy for breast cancer

We investigated the prophylactic antiemetic effect of added low-dose infusion of propofol in patients exhibiting nausea and vomiting refractory to dexamethasone and serotonin antagonist during non-cisplatin chemotherapy for breast cancer. In a prospective open longitudinal study, 117 patients who had more than five episodes of nausea and vomiting in their first chemotherapy cycle during the first 24 hr completed the study. They received in addition to the usual prophylactic antiemetic regimen a continuous intravenous infusion of 1 mg.kg-1.hr-1 propofol started four hours before chemotherapy and continued up to 24 hr for the two subsequent cycles. The number of vomiting/nausea episodes, level of sedation, patient activity, appetite and preference for future chemotherapy cycles were assessed. In the propofol supplemented cycles 90 and 80% of patients, during the 1st and 2nd propofol-assisted cycle respectively, were free of nausea and vomiting during the first 24 hr after chemotherapy. Patients were more frequently active and had more appetite during the propofol-assisted cycles. No propofol-associated side effects were observed. We conclude that the addition of a subhypnotic infusion of propofol enables better control of nausea and vomiting caused by non-cisplatin chemotherapy in the first 24 hr post-treatment.

Prophylactic Antiemetic Therapy with Patient-Controlled Analgesia

This placebo-controlled, randomized, double-blind trial was designed to evaluate the efficacy of three prophylactic antiemetic regimens on postoperative nausea and vomiting (PONV) during patient-controlled analgesia (PCA) with morphine. We studied 286 elective surgical patients for 36 h postoperatively. Group 1 was saline control. In Groups 2 and 3, metoclopramide or droperidol was administered as an intravenous (i.v.) bolus and then added to morphine in the PCA device. In Group 4, tropisetron, a long-acting investigational 5-hydroxytryptamine subtype 3 (5-HT3) antagonist was given as a single i.v. dose. We assessed the frequency and severity of PONV, as well as the need for rescue, frequency of side effects, and overall patient satisfaction. Severity of PONV was measured with a symptom-severity score (STS) which was based on both intensity and duration. The average total doses of antiemetics were metoclopramide 53.8 +/- 2.2 mg, droperidol 5.99 +/- 0.3 mg, and tropisetron 6.1 +/- 0.2 mg. Control patients had a 54% incidence of PONV. Droperidol reduced both the incidence (P < 0.001) and severity (P < 0.01) of PONV for the entire 36 h. Tropisetron reduced incidence and severity (P < 0.05), but the effect of the single bolus dose lasted only 18 h. Metoclopramide had a marginally significant effect under these conditions. Only droperidol decreased the need for rescue medication (P < 0.01), although rescue with tropisetron was highly effective. Side effects and patient satisfaction were comparable among the groups, but patients receiving droperidol were sleepier (P < 0.05) than control patients and recalled somewhat more anxiety (P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Prophylactic antiemetic regimens for chemotherapy-induced emesis

Prophylactic antiemetic regimens for chemotherapy-induced emesis

Oral metoclopramide with or without diphenhydramine: potential for prevention of late nausea and vomiting induced by cisplatin.

Late nausea and vomiting lasting 2-7 days occurs in 20%-68% of patients receiving cisplatin. We therefore studied the effects of oral metoclopramide given at doses of 20, 50, or 100 mg four times a day for 25 doses (7 days) beginning after cisplatin to determine the maximum tolerated dose (MTD) for prophylactic oral antiemetic regimens. Patients were stratified into younger (less than or equal to 30 yr old) and older (greater than 30 yr old) groups. Dose escalation was performed without or with concomitant oral diphenhydramine. For the younger group, the MTD for metoclopramide without diphenhydramine was less than 20 mg, and the MTD with diphenhydramine was 20 mg. For the older group, the MTD without diphenhydramine was 20 mg, and the MTD with diphenhydramine was 50 mg. Extrapyramidal reactions in the younger group and agitated depression in the older group were the major dose-terminating toxic effects. Patient acceptance of these regimens was excellent.