An open-label dose comparison study of ondansetron for the prevention of emesis associated with chemotherapy prior to bone marrow transplantation

Stem cell transplantation, using high-dose chemotherapy with or without TBI, is usually associated with significant nausea and vomiting. A variety of antiemetic regimens have been studied to control nausea and vomiting associated with the preparative therapy phase of SCT. We review the most significant studies and highlight the limitations of many of these studies. In addition, we review the few studies with the use of aprepitant as an antiemetic in combination with a 5HT 3 antagonist and a steroid. The American Society of Clinical Oncology guideline for antiemetic use for treatment regimens that are highly emetogenic is reviewed regarding recommendations for SCT preparative regimens. On the basis of this review of published data, we recommend the basic outline for an effective antiemetic investigational approach to the study and to the control of nausea and vomiting during the preparative phase of treatment for SCT.

Section: Resultsmentioning

confidence: 99%

Nausea and vomiting with high-dose chemotherapy and stem cell rescue therapy: a review of antiemetic regimens

Trigg

Inverso

2008

“…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.…”

mentioning

confidence: 99%

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

Walsh

Morris

Holle

et al. 2004

Summary:The serotonin type-3 (5-HT 3 ) antagonists represent a significant advance in the prevention of acute nausea and vomiting (N/V) from highly emetogenic chemotherapy. We sought to determine if any differences in efficacy or adverse effects exist between two such agents, ondansetron and granisetron, during conditioning therapy for hematopoietic stem cell transplantation (HSCT). Patients were randomized to receive either ondansetron 0.15 mg/kg intravenously every 8 h or granisetron 10 lg/kg intravenously daily. Additionally, all patients received scheduled dexamethasone and lorazepam. Prophylaxis was continued until 24 h after completion of chemotherapy. Nausea and distress were measured subjectively with visual analog scales and emetic episodes were quantified. Of the 110 randomized patients, 96 were evaluable for efficacy and safety. No significant differences in efficacy were observed between the ondansetron-and granisetron-treated patients, evaluated by comparing the degree of nausea and distress, number of emetic episodes and overall control of emesis. The adverse effects were also comparable and no patients were removed from study because of severe toxicities. This trial demonstrates that ondansetron and granisetron are equally effective at preventing acute N/V associated with conditioning therapy frequently used for HSCT. The agent of choice should be based on drug acquisition cost or preference.

“…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.…”

Section: Discussionmentioning

confidence: 81%

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

Ballen

Hesketh

Heyes

et al. 2001

Summary:Considerable progress has been made in improving the control of chemotherapy-induced emesis. The impact of available antiemetic options for patients receiving stem cell transplants is unclear, as few prospective data have been collected. We prospectively evaluated antiemetic outcome in patients receiving stem cell transplantation over a 7-day period following the initiation of chemotherapy. The primary endpoints were the number of emetic episodes and the extent of nausea measured on a four-point scale. Eighty-two patients were evaluated. Ninety-five percent of patients had nausea during the first week of treatment; 80% had at least one emetic episode. The percentage of patients with emesis was as follows: day 1: 13%, day 2: 21%, day 3: 30%, day 4: 38%, day 5: 44%, day 6: 39%, day 7: 18%. In multivariate analysis, gender, emesis with prior chemotherapy, history of morning or motion sickness, type of transplant (auto vs allo), use of total body irradiation, or use of dexamethasone did not effect emesis control. Most patients receiving high-dose chemotherapy experience incompletely controlled emesis. Control of nausea and emesis progressively worsened with each subsequent day following initiation of chemotherapy, reaching a nadir on day 5. New treatment approaches are needed to improve emesis control in this patient population. Bone Marrow Transplantation (2001) 28, 1061-1066. Keywords: nausea; bone marrow transplantation Myeloablative chemotherapy and radiotherapy followed by autologous or allogeneic stem cell transplantation have been shown to be curative for certain hematologic malignancies, aplastic anemia, and genetic disorders. 1-3 Over the last three decades of transplantation, there have been significant advances in supportive management to lessen tox- icity and improve tolerance of autologous and allogeneic stem cell transplantation. [4][5][6][7] From the patient's standpoint, two of the most feared adverse effects of chemotherapy are treatment-induced nausea and vomiting. 8,9 Considerable progress has been made in the control of nausea and vomiting for patients receiving standard doses of chemotherapy. The use of 5-hydroxytryptamine-3 (5HT3) antagonists, such as dolasetron, granisetron and ondansetron, have contributed significantly to the control of nausea and vomiting in patients receiving moderately and highly emetogenic chemotherapy. [10][11][12][13] The great majority of patients receiving emetogenic chemotherapy at standard doses should achieve complete control of emesis at the present time.A number of patient and treatment-related factors predictive for the development of chemotherapy-induced emesis have been defined. These include age, gender, ethanol consumption history, and the intrinsic emetogenicity of the chemotherapy agents. 14 Also of importance is chemotherapy dose. The emetogenicity of a number of chemotherapy agents such as cisplatin and cyclophosphamide increases with increasing dose. 15 The outcome of antiemetic therapy has not been well studied in the setting of highdose chemo...