Antiemetic Efficacy Of Granisetron Research Articles

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.

Retraction Note to: Antiemetic efficacy of granisetron and metoclopramide in children undergoing ophthalmic or ENT surgery

Further to the Expression of Concern posted online on March 13th, 2012, it is with considerable regret that the Canadian Journal of Anesthesia hereby retracts the above-cited article by Dr. Yoshitaka Fujii as a result of:(1) overwhelming evidence of fabrication relating to the fact that the distributions of many variables reported by Dr. Fujii in these studies are exceedingly unlikely; and the inability of Dr. Fujii’s institution to attest to the integrity of the study and/or the data conducted under its auspices, as set out in the Joint Editors-in-Chief Request for Determination of April 9, 2012. We extend our sincere appreciation to Toride Kyodo General Hospital for their review of the status of Dr. Fujii’s research and to the investigating committee for their review of his research findings.

COMPARISON OF TROPISETRON AND GRANISETRON IN THE CONTROL OF NAUSEA AND VOMITING IN CHILDREN RECEIVING COMBINED CANCER CHEMOTHERAPY

Tropisetron and granisetron are selective serotonin (5-HT 3 ) antagonists that have been proven effective in the prevention of nausea and vomiting in adults and children receiving cancer chemotherapy. This prospective, randomised study was designed to compare the efficacy of the two agents in the prevention of vomiting and nausea in children receiving highly emetogenic chemotherapy for various malignancies. A total of 51 children (mean age: 7.7 - 4.8 year) were studied in 133 chemotherapy cycles. In 66 chemotherapy cycles, the children received tropisetron as an antiemetic agent in a dose of 0.2 mg/kg/24 h intravenously and, in 67 cycles, they received granisetron 40 w g/kg/24 h intravenously before cytotoxic drug administration during the days they received chemotherapy. The response per 24 h of chemotherapy was defined as complete (no nausea and vomiting), partial (1-4 events of vomiting and/or nausea), and failure (more than 4 events o fvomiting and/or nausea). Efficacy of antiemetic therapy was evaluatedas acute (Day 1) and overall was based on the worst day during the chemotherapy. Complete control of acute vomiting was achieved in 74% of tropisetron and 88% of granisetron patients ( P = 0.04), and complete control of acute nausea in 56% and 82% respectively ( p = 0.002). Overall response by means of complete control of both vomiting and nausea during the whole therapy period was 29% of tropisetron group and 55% of granisetron group ( p = 0.007). The statistical analysis (depending on the emetogenicity of the chemotherapy cycles) showed increased efficacy of granisetron in highly (grade 3) emetogenic chemotherapy cycles ( p = 0.002), whereas there was no differencein the very highly emetogenic cycles ( p = 0.7). Also, granisetron was found to be more effective than tropisetron, especially in patients heavier than 25 kg ( p = 0.02). The adverse reactions were few and mild. There were no differences in the tolerability of the two antiemetic therapy modalities. In conclusion, granisetron was found to be more effective than tropisetron in controlling nausea and vomiting in children receiving highly emetogenic chemotherapy. This increased antiemetic efficacy of granisetron might have been related to maximal dose differences according to body weight.

Cisplatin-induced emesis in the cat: effect of granisetron and dexamethasone

The emetic action of cisplatin was investigated in the cat using a closed circuit video recording system. In initial investigations, cisplatin 3 and 5 mg/kg, i.v. induced emesis over a 2-day period following a latency of 17.6±9.6 and 15.6±7.8 h, respectively. The anti-emetic efficacy of granisetron and dexamethasone was investigated in the cisplatin 5 mg/kg, i.v.-induced emesis model. In these experiments, cisplatin induced 47.0±14.0 and 20.0±9.0 retches+vomits on days 1 and 2, respectively, following a latency of 2.4±0.4 h. Granisetron (1 mg/kg, i.m.) administered three times per day reduced significantly the retching+vomiting response induced by cisplatin on days 1 and 2 by 100.0% ( P<0.05) and 75.0% ( P<0.05), respectively; dexamethasone (0.01–1 mg/kg, i.m.) administered three times per day reduced significantly the retching+vomiting response by 68.8–100.0% ( P<0.05) and 33.3–100.0% ( P<0.05) on days 1 and 2, respectively. The emetic action of cisplatin 7.5 mg/kg, i.v. was also investigated. This dose of cisplatin-induced emesis following a latency of 1.2±0.2 h and comprised 119.0±20.8 retches+vomits over a 24-h period. Granisetron and dexamethasone antagonized the emesis occurring in the first 3-h period ( P<0.05) but were less effective to antagonize the subsequent emetic response ( P>0.05). The pharmacological sensitivity of low dose cisplatin-induced emesis in the cat is variable but unique and not representative of the clinical situation.

Antiemetic efficacy of granisetron plus dexamethasone in bone marrow transplant patients receiving chemotherapy and total body irradiation

Few trials exist regarding the antiemetic efficacy of granisetron in bone marrow transplant (BMT) recipients conditioned with high-dose chemotherapy and total body irradiation (TBI). In this single-center, open-label, prospective, trial, the antiemetic efficacy and safety of granisetron plus dexamethasone were evaluated in 26 patients conditioned with cyclophosphamide-containing regimens (the majority receiving 60 mg/kg per day on 2 consecutive days), and TBI (12 Gy divided over 4 days). Daily intravenous doses of granisetron 1 mg plus dexamethasone 10 mg were given 30 min prior to chemotherapy or radiation, and continued for 24 h after the last conditioning treatment for a median of 6 days (range 3-9). Emetic control was defined by the number of emetic episodes occurring within a 24 h period, or the requirement for rescue medication for nausea or vomiting. A total of 25 patients completed 186 evaluable treatment days. Response (emetic control by treatment days) was complete in 50% of patients, major in 48%, minor in 2%, and there were no failures. Adverse effects were minor, with diarrhea (15%), headache (14%), and constipation (11%) reported most often. Based on these results, the antiemetic regimen of granisetron plus dexamethasone appears effective and well tolerated during BMT conditioning with high-dose cyclophosphamide and TBI.

Anti-emetic efficacy of prophylactic granisetron, droperidol and metoclopramide in the prevention of nausea and vomiting after laparoscopic cholecystectomy: a randomized, double-blind, placebo-controlled trial

This study evaluates the prophylactic anti-emetic efficacy of granisetron, droperidol and metoclopramide, for the prevention of post-operative nausea and vomiting in female patients undergoing elective laparoscopic cholecystectomy. The patients were randomly assigned to one of four groups (n = 30 for each group): granisetron 3 mg, droperidol 1.25 mg, metoclopramide 10 mg and placebo (saline). These medications were given immediately before the induction of anaesthesia. During the first 24 h after anaesthesia, the incidence of post-operative nausea and vomiting was 13, 30, 33 and 37% after administration of granisetron, droperidol, metoclopramide and placebo, respectively (P < 0.05, overall Fisher's exact probability test). No clinically important adverse effects were observed in either group. Our results suggest that granisetron is a better anti-emetic than droperidol or metoclopramide for the prevention of post-operative nausea and vomiting after laparoscopic cholecystectomy when compared with a placebo.

812 Randomized comparison of the antiemetic efficacy of granisetron plus methyl prednisolone sodium succinate with granisetron alone for the prevention of cisplatin-induced emesis in patients with advanced stage III non-small cell lung cancer

812 Randomized comparison of the antiemetic efficacy of granisetron plus methyl prednisolone sodium succinate with granisetron alone for the prevention of cisplatin-induced emesis in patients with advanced stage III non-small cell lung cancer

Dexamethasone improves the efficacy of granisetron in the first 24 h following high-dose cisplatin chemotherapy

The object of the study was to determine whether dexamethasone improved the efficacy of the serotonin receptor (5-HT3) antagonist granisetron in controlling acute (within 24 h) emesis in cancer patients receiving high-dose cisplatin chemotherapy and to ascertain whether continuation of granisetron after 24 h reduces the occurrence of delayed emesis. This randomised, double-blind, multicentre, three-arm study was conducted at 21 medical centres. A group of 292 nausea- and emesis-free patients with cancer, who had never had chemotherapy and were scheduled to receive at least 50 mg/m2 cisplatin, were given 3 mg granisetron i.v. in a 15-min infusion with or without 10 mg dexamethasone i.v. completed 5 min prior to high-dose cisplatin and 1 mg granisetron p.o. at +6 h and +12 h. Primary study end-points were control of emesis and nausea. Patients completed a self-report diary every 6 h for the first 24 h. At the end of the 24-h period, the patients who received dexamethasone had a significantly higher complete protection rate from emesis (64% compared to 39%) than those who received no steroid. Similarly, the dexamethasone-treated group had a significantly higher complete plus partial (0-2 emetic episodes) protection rate (84% compared to 64%). This study shows that dexamethasone markedly enhances the antiemetic efficacy of granisetron for acute-onset emesis in high-dose cisplatin chemotherapy.

Possible cardiac side effects of granisetron, an antiemetic agent, in patients with bone and soft-tissue sarcomas receiving cytotoxic chemotherapy.

The cardiac effect of granisetron, a selective 5-hydroxytryptamine3 receptor antagonist, on 12 patients with bone and soft-tissue sarcomas treated by cytotoxic chemotherapy consisting of multiple courses was examined. Of the 12 patients, 4 showed significant electrocardiographical changes, including sinus bradycardia, integral change of P-waves, junctional escape beat, and atrioventricular (AV) block with Wenckebach phenomenon, indicating stimulatory regulation of the vagus nerve. These changes were observed in each patient after several courses of chemotherapy but not in the first course. There was no correlation between the electrocardiographical changes and the chemotherapeutic agents used or the type of tumor present. A patient with osteosarcoma showed persistent bradycardia in three courses, all protocols of which contained high-dose methotrexate. From these findings we conclude that the cardiac responses may be due to stimulated activity of the vagal efferent nerve, which is regulated reflexly by afferent nerve activity suppressed by granisetron. On the other hand, the antiemetic efficacy of granisetron was satisfactory. These results suggest that careful observation of the heart is necessary when granisetron is used, especially for chemotherapy consisting of repeated multiple courses.

Granisetron, ein neues und potentes Antiemetikum zur Behandlung der zytostatikainduzierten Emesis gynäkologischer Malignome

The efficacy of Granisetron, a new and selective 5HT3-receptor-antagonist in the treatment of cytostatic induced emesis, was tested in the department of gynaecology and obstetrics of the University of Essen on 77 patients. The patients received cytostatic drugs with a high emetogenic potency (for example cisplatin) or with a moderately high emetogenic potency (for example cyclophosphamide). We were able to demonstrate the high antiemetic efficacy of Granisetron. We had in 63% of the cases a "complete response" during the first 24 h after the chemotherapy and a "complete response" of 60% for the "delayed emesis". The observed adverse reactions such as constipation and headache were easily solved with standard laxatives or standard analgesics. Because of the high efficacy of Granisetron, which was combined with a low rate of side effects, it was possible to give to all the 77 patients the complete and necessary chemotherapy, so that no patient refused to receive the chemotherapy just because of nausea or emesis. The use of Granisetron is therefore a major step forward in the care of patients receiving chemotherapy because nausea and emesis can be treated effectively.