Granisetron (Kytril) plus dexamethasone for antiemetic control in bone marrow transplant patients receiving highly emetogenic chemotherapy with or without total body irradiation

Abstract

Keywords: antiemetic; bone marrow transplant; chemotherapy; dexamethasone; granisetron; total body irradiation Nausea, retching, and emesis are some of the most common unwanted effects associated with chemotherapy. These treatment side-effects represent a significant concern to the cancer patient.1 Nausea and vomiting are contributing factors to patient morbidity, and are critical factors in the patient's quality of life during treatment. Additionally, emetic episodes often influence the continuation of treatment.2 Fortunately, with the advent of the serotonin antagonists, there has been a major improvement in the control of nausea and vomiting.3 Granisetron is a potent, selective 5-hydroxytrypamine 3 (5-HT 3 ) receptor antagonist that has activity both in the periphery on the abdominal vagal afferents, and centrally on the chemoreceptor trigger zone (CTZ). Emesis occurs when the vomiting center is stimulated by the CTZ or by afferent impulses from the cerebral cortex, gastrointestinal tract, heart, or vestibular apparatus. 4Several receptor types have been identified in these regions, including dopaminergic, cholinergic, histaminergic, opioid, and serotonergic (5-HT 3 ). 5 Chemotherapy and radiotherapy cause cellular damage, eliciting a release of serotonin from enterochromaffin cells in the intestinal mucosa. Serotonin release also activates 5-HT 3 receptors in the vagal and possibly splanchnic afferent neurons through agonism with resultant stimulation of the CTZ, causing the vomiting reflex.6 Granisetron controls chemotherapy-induced nausea and vomiting via competitive antagonism of serotonin at the 5-HT 3 receptors. 7Granisetron is FDA-approved for the prevention of nausea and vomiting associated with initial and repeated courses of emetogenic cancer chemotherapy. Several trials have addressed the antiemetic efficacy of serotonin antagonists for the prevention of irradiation-induced emesis. [7][8][9][10][11] The controversies that currently exist regarding granisetron use in this patient population include optimal dose and optimal dosing frequency. 11,12The main objectives of this trial were to monitor the emetic control of granisetron plus dexamethasone in patients who received chemotherapy regimens containing high-dose CY with or without TBI as a preparative regimen for BM or PBSC transplantation or PBSC mobilization, and evaluate any adverse effects of the combination. Patients and methods Study designThis study was a single-center, open-label, prospective trial approved by the Institutional Review Board. Written informed consent was obtained from all patients prior to enrollment. All patients had either a hematologic or oncologic malignancy. Patients were eligible if they were receiving any high-dose chemotherapy preparative regimen containing cyclophosphamide (CY) (у60 mg/kg/day or у1.5 g/m 2 /day) with or without TBI (12 Gy divided over 4 days), followed by BM or PBSC transplantation or PBSC mobilizaton. Additionally, patients had to be 16 years or

Granisetron vs ondansetron for prevention of nausea and vomiting in hematopoietic stem cell transplant patients: results of a prospective, double-blind, randomized trial

“…These studies have substantiated the efficacy of granisetron and ondansetron for prevention of N/V associated with high-dose conditioning regimens, however, different dosing strategies and end points have made comparisons of these results difficult. One such study was conducted by Abbott et al 18 and evaluated the efficacy of intravenous granisetron plus intravenous dexamethasone 10 mg administered daily until 24 h after conditioning therapy was complete. Only 1% of 100 patients enrolled failed to respond, however, the response criteria were different than those used in our study.…”

“…Outside of the HSCT setting, numerous studies have concluded that these agents provide equivalent control of N/V induced by highly emetogenic chemotherapy when administered at equipotent doses. [2][3][4][5][6][7][8] Although three of these agents have been extensively studied in HSCT patients over the last 8 years, [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] limited data directly comparing these agents is available. [21][22][23] Ondansetron, the first 5-HT 3 receptor antagonist approved in the United States, has been the most widely studied and is most effectively used in combination with corticosteroids for prevention of CINV; granisetron's effects are also enhanced with the use of corticosteroids.…”

Prospective evaluation of antiemetic outcome following high-dose chemotherapy with hematopoietic stem cell support

“…19 For patients receiving high-dose chemotherapy or chemo/ radiotherapy regimens in association with hematopoietic stem cell support, a number of studies suggest that antiemetic control may be a greater challenge in this setting. 17,[20][21][22][23][24][25] In the current prospective trial, we have clearly demonstrated that despite the use of standard prophylactic treatments, antiemetic control is indeed suboptimal for patients receiving allogeneic or autologous hematopoietic stem cell transplants and appears to be inferior to the results obtained with standard-dose chemotherapy. Limitations of the study include the diverse conditioning regimens, antiemetic treatments, and small sample size.…”

“…14 Other prospective studies did not analyze these predictive factors. 22,23 Of note, none were found to have a significant impact. There was a trend toward less emesis in patients receiving dexamethasone and perhaps this would have achieved significance with a larger patient sample.…”

Effectiveness and Safety of Antiemetic Aprepitant in Japanese Patients Receiving High-Dose Chemotherapy Prior to Autologous Hematopoietic Stem Cell Transplantation

“…[2][3][4] However, a number of recipients still suffer from uncontrollable CINV. [5][6][7][8][9][10] Therefore, additional options to reduce CINV in these patients are needed.…”