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The serotonin type-3 (5-HT3) 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 cel...
Context in source publication
Context 1
... median number of emetic episodes was 3 (range, 0-15) for the granisetron-treated group and 1 (range, 0-9) for the ondansetron-treated group (P ¼ 0.228). The overall control of emesis was similar between treatment groups (Table 3). Although control of emesis declined throughout the study period, the majority of patients had a complete or major response. ...
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Citations
... Rolapitant is a new oral NK1R inhibitor with a longer plasma half-life (approximately 7 days) and no CYP3A4 inhibition. It was tested in two phase III studies in combination with 5-HT3 inhibitor and dexamethasone in patients receiving highly and (Orchard et al. 1999) 197 Autologous, allogeneic 63% versus 61% (p = 0.68) Granisetron versus ondansetron (Walsh et al. 2004) 96 ...
Hematopoietic stem cell transplant results in a variety of treatment-related side effects other than pain. The side effects encountered may include prolonged, late, or permanent side effects of prior cancer therapy in addition to treatment-related effects from transplant chemotherapy, prolonged cytopenias, and therapy used for supportive care during transplant. Systemic side effects to address during and after transplant may include fatigue, delirium, and malnutrition. Gastrointestinal side effects may include mucositis, nausea, vomiting, diarrhea, and constipation. In this chapter we discuss the recognition, approach, and therapeutic interventions for the management of these non-pain-related side effects of Hematopoietic stem cell transplant.
... Prospective randomized trials in pediatric and adult patients undergoing autologous or allogeneic HSCT did not detect statistically significant difference between the antiemetic efficacy of granisetron and ondansetron. [32][33][34] Although the efficacy analysis of the control and the fosaprepitant group showed that the percentage of pediatric patients experiencing vomiting was only lower in the second time period >24-120h (100% vs 74.3%), a clear benefit of the addition of fosaprepitant was demonstrated: besides the significant reduction of vomiting events in all three analyzed time periods (0-24h: 2.9-fold reduction | >24-120h: 1.7-fold reduction | >120-240h: 2.6-fold reduction | 0-240h: 2.3-fold reduction), the use of antiemetic on-demand medication with dimenhydrinate (333 vs 143 doses), and levomepromazine perfusor (17 vs 5 days use of perfusor) was reduced. ...
Background
High-dose myeloablative conditioning prior to autologous hematopoietic stem cell transplantation (autoHSCT) in pediatric patients is usually highly emetogenic. The antiemetic neurokinin-1 receptor antagonist fosaprepitant was safe and effective in children receiving highly emetogenic chemotherapy. Data on fosaprepitant during autoHSCT in children are currently not available.
Methods
A total of 35 consecutive pediatric patients, who received an antiemetic prophylaxis with fosaprepitant (4 mg/kg; single dose, max. 1 x 150 mg/kg BW) and ondansetron (24-hours continuous infusion; 8–32 mg/24h) or granisetron (2 x 40 µg/kg∙d⁻¹) during highly emetogenic conditioning chemotherapy before autoHSCT were retrospectively analyzed, and their results were compared with a control group comprising 35 consecutive pediatric patients, who received granisetron or ondansetron only. The antiemetic efficacy and the safety of the two prophylaxis regimens were compared with respect to three time periods after the first chemotherapy administration (0–24h, >24–120h, >120–240h).
Results
Clinical adverse events and clinically relevant increases/decreases of laboratory markers were similarly low and did not significantly differ between the two study groups (p>0.05). The registered number of vomiting events was significantly higher in the control group in the time periods of 0–24h (64 vs 22 events; p<0.01), >24–120h (135 vs 78 events; p<0.0001), >120–240h (268 vs 105 events; p<0.0001), and the whole observation period 0–240h (467 vs 205 events; p<0.0001). The percentage of patients experiencing vomiting was higher in the control group during the time period of >24–120h (100% vs 74.3%) but not the other analyzed time periods (p>0.05).
Conclusion
The fosaprepitant-based antiemetic prophylaxis was safe, well tolerated and significantly reduced vomiting in children undergoing highly emetogenic chemotherapy prior to autoHSCT. Prospective randomized trials are necessary to confirm these results.
... [2][3][4] Although the combination of dexamethasone plus a 5-HT 3 receptor antagonist is often used prior to HSCT, vomiting is not controlled in as many as 80-93% of patients. [5][6][7][8][9][10][11][12][13] Since the neurokinin-1 receptor antagonist aprepitant was approved, the use of triple combination antiemetic therapy (i.e., dexamethasone, 5-HT 3 receptor antagonist, and aprepitant) has resulted in further improvements in the control of CINV in non-HSCT patients with solid tumors who are treated with moderate to highly emetogenic chemotherapy. [14][15][16] In addition, aprepitant has been recently reported to prevent CINV associated with high-dose preparative regimens followed by HSCT. ...
Study objective:
To evaluate the efficacy and safety of aprepitant added to standard antiemetic regimens used in high-dose chemotherapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Design:
Retrospective medical record review.
Setting:
Hematology ward of a university hospital in Japan.
Patients:
Of 88 patients treated with high-dose chemotherapy followed by allo-HSCT, 46 received aprepitant and granisetron as antiemetic therapy (between April 1, 2010, and December 31, 2011), and 42 received granisetron alone (between April 1, 2008, and March 31, 2010).
Interventions:
Patients in both groups received 3 mg of granisetron intravenously 30 minutes before the administration of anticancer drugs. In the aprepitant group, 125 mg of aprepitant was administered orally 60-90 minutes before the administration of the first moderately to highly emetogenic anticancer drug. On the following days, 80 mg of aprepitant was administered orally every morning. The mean administration duration of aprepitant was 3.3 days (range 3-6 days).
Measurements and main results:
The primary objective was to evaluate the percentage of patients who achieved complete response (CR; no vomiting and none to mild nausea). The CR rate in the aprepitant group was significantly higher than that in the control group (48% vs 24%, p=0.02). Multivariate analysis showed that nonprophylactic use of aprepitant was associated with failure to achieve CR (odds ratio [OR] 2.92; 95% confidence interval [CI] 1.13-7.99, p=0.03). The frequency of abdominal pain was lower in the aprepitant group (9% vs 25%, p=0.03). Rates of other frequently observed adverse drug events were similar between groups. There was no significant difference in neutrophil engraftment (median 18 vs 17 days), platelet engraftment (median 32 vs 32 days), the incidence of acute graft-versus-host-disease (63% vs 55%, p=0.52), viral infection (74% vs 67%, p=0.49), or 1-year overall survival (63% vs 62%, p=0.90) between the two groups.
Conclusions:
The addition of aprepitant to granisetron increases the antiemetic effect without influencing transplantation-related toxicities in allo-HSCT.
... 22,23 A number of studies assessed special populations. Three trials detailed results in patients undergoing myeloablative therapy before transplant, [24][25][26] two described efforts in patients receiving multiday chemotherapy regimens, 27,28 and three trials evaluated antiemetic therapies in pediatric patients undergoing cancer therapy. [29][30][31] Three studies examined complementary therapies in patients receiving cancer treatment. ...
Overview
In 2011, ASCO updated its guideline for the use of antiemetics in oncology, informed by a systematic review of the medical literature. This is an abbreviated version of that guideline, which is available in full at www.asco.org/guidelines/antiemetics . Key changes from the prior update in 2006 include the following: Combined anthracycline and cyclophosphamide regimens were reclassified as highly emetic. Patients who receive this combination or any highly emetic agents should receive a 5-HT 3 receptor antagonist, dexamethasone, and an NK 1 receptor antagonist. A large trial validated the equivalency of fosaprepitant, a single-day intravenous formulation, with aprepitant; either therapy is appropriate. Preferential use of palonosetron is recommended for moderate emetic risk regimens, combined with dexamethasone. For low-risk agents, patients can be offered dexamethasone before the first dose of chemotherapy. Patients undergoing high emetic risk radiation therapy should receive a 5-HT 3 receptor antagonist before each fraction and for 24 hours following treatment and may receive a 5-day course of dexamethasone during fractions 1 to 5. Continued symptom monitoring throughout therapy is recommended. Clinicians often underestimate the incidence of nausea, which is not as well controlled as vomiting. Detailed information about the development of the guideline as well as practice tools are available at www.asco.org/guidelines/antiemetics .
... 22,23 A number of studies assessed special populations. Three trials detailed results in patients undergoing myeloablative therapy before transplant, [24][25][26] two described efforts in patients receiving multiday chemotherapy regimens, 27,28 and three trials evaluated antiemetic therapies in pediatric patients undergoing cancer therapy. [29][30][31] Three studies examined complementary therapies in patients receiving cancer treatment. ...
In 2011, ASCO updated its guideline for the use of antiemetics in oncology, informed by a systematic review of the medical literature. This is an abbreviated version of that guideline, which is available in full at www.asco.org/guidelines/antiemetics. Key changes from the prior update in 2006 include the following: Combined anthracycline and cyclophosphamide regimens were reclassified as highly emetic. Patients who receive this combination or any highly emetic agents should receive a 5-HT3 receptor antagonist, dexamethasone, and an NK1 receptor antagonist. A large trial validated the equivalency of fosaprepitant, a single-day intravenous formulation, with aprepitant; either therapy is appropriate. Preferential use of palonosetron is recommended for moderate emetic risk regimens, combined with dexamethasone. For low-risk agents, patients can be offered dexamethasone before the first dose of chemotherapy. Patients undergoing high emetic risk radiation therapy should receive a 5-HT3 receptor antagonist before each fraction and for 24 hours following treatment and may receive a 5-day course of dexamethasone during fractions 1 to 5. Continued symptom monitoring throughout therapy is recommended. Clinicians often underestimate the incidence of nausea, which is not as well controlled as vomiting. Detailed information about the development of the guideline as well as practice tools are available at www.asco.org/guidelines/antiemetics.
... 2 A number of studies have been published regarding control of nausea and vomiting during the time when such therapy is delivered up until or shortly after the stem cell infusion. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Variable degrees of success regarding control of nausea and vomiting have been reported, with many agents, including serotonin antagonists such as granisetron and ondansetron. Often, patients undergoing these therapies with high-dose chemotherapy, with or without radiation, have had a long history of similar types of therapy with variable control of nausea and vomiting. ...
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.
... 40,41 Because of the very low response rate, dexamethasone has been added to the 5-HT3 receptor antagonists and each has been given on a daily basis during high-dose chemotherapy. The complete response rate appeared to improve 20% to 50% in various studies [42][43][44][45][46] with the addition of dexamethasone. The various first-generation 5-HT3 receptor antagonists used with or without dexamethasone seem to show no difference in complete response. ...
... The various first-generation 5-HT3 receptor antagonists used with or without dexamethasone seem to show no difference in complete response. 44,47 Control of nausea and vomiting in patients undergoing high-dose chemotherapy and stem cell transplantation is a significant challenge, with past studies showing limited success. Current standard therapy seems to be a first-generation 5-HT3 receptor antagonist and dexamethasone, each given daily during the chemotherapy regimen. ...
The prevention of chemotherapy-induced nausea and vomiting (CINV) has improved significantly with the introduction of the 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists combined with dexamethasone. Most studies have reported on patients undergoing single-day highly or moderately emetogenic chemotherapy. There have been fewer studies and much less success in preventing CINV in patients undergoing multiple-day chemotherapy or high-dose chemotherapy with stem cell transplant. Current practice guidelines suggest the use of a first-generation 5-HT3 receptor antagonist and dexamethasone daily for each day of the multiple-day chemotherapy regimens. This practice seems to control acute CINV, but delayed CINV remains poorly controlled with a complete response (e.g., no emesis, no rescue) of less than 50% in most studies. Three new agents-palonosetron, aprepitant, and olanzapine-have shown high efficacy in preventing acute and delayed CINV in patients undergoing single-day chemotherapy. These agents have high potential for preventing CINV in patients undergoing multiple-day chemotherapy. This article proposes recommendations for their use in clinical trials and in practice.
... , who comprise 5-12% of patients in this and some other studies; 16,19 (ii) the inclusion of patients with central nervous system pathology and those in whom potential emetogenic procedures such as lumbar punctures were performed; and (iii) the widespread use of total body irradiation (26% of patients), which is more emetogenic than other schemes. 19,20 The intensity of emesis in our study was high, especially among transplant recipients. These results are similar to other published data, although children and recipients of non-total body irradiation regimens experience a more benign course, 16,21 and not very different from those reported in some studies in the pre-5HT3- antagonist ...
The aim of this study was to evaluate the incidence and severity of chemotherapy-induced nausea and vomiting (CINV) in oncohematology in routine clinical practice, its impact on quality of life, and caregivers' perception of the extent of the problem.
This was a multicenter, prospective, observational follow-up study including: (i) acute myeloid leukemia patients treated with moderately to highly emetogenic chemotherapy and (ii) hematopoietic stem cell transplant recipients, without reduced intensity conditioning. No exclusion criteria were applied. All patients received at least one 5-HT3 antagonist for emesis prophylaxis. Patients recorded emetic episodes and rated nausea daily. Quality of life was assessed through a validated functional living Index-Emesis questionnaire. A survey of caregivers' predictions of CINV was made and the predictions then compared with the observed CINV.
One hundred consecutive transplant and 77 acute myeloid leukemia patients were studied. Transplant conditioning was the most important risk factor for CINV: complete response occurred in only 20% of transplant patients (vs. 47% for leukemia patients). Among patients with emesis, the mean percentage of days with emesis and the mean (+/-SD) total number of emetic episodes were 61% and 9.4+/-8.9 (transplant recipients), and 53.6% and 6.2+/-7.3 (leukemia patients), respectively. CINV control was lower in the delayed than in the acute phase. Antiemetic rescue therapy was ineffective. CINV had a deleterious effect on quality of life, especially among transplant recipients. Caregivers underestimated the incidence of delayed nausea and emesis in the transplant setting.
Despite 5-HT3 antagonist prophylaxis, CINV remains a significant problem in oncohematology, especially in the delayed phase and in transplant recipients.
High-dose chemotherapy involves the administration of potentially toxic doses of chemotherapeutic agents in an effort to eradicate cancer cells. A wide range of high-dose regimens has been developed and they typically consist of several agents given at high doses over 2–7 days. The use of peripheral blood as a source of stem cells for autologous hematopoietic stem-cell transplantation (HSCT) greatly contributed to the application of myeloablative chemotherapy in the treatment of both hematological and solid malignancies. In the setting of HSCT, chemotherapy-induced nausea and vomiting (CINV) are almost universal and may occur not only during administration of anticancer agents but also for days or weeks during the recovery period from chemotherapy. In addition, irradiation used in many preparative regimens is associated with a number of acute side effects that include nausea and vomiting, compounding the side effects of chemotherapy. Therefore, high-dose multiple-day chemotherapy with HSCT provides a unique challenge to achieving good antiemetic control and remains one of the neglected areas of antiemetic research. There are difficulties in developing evidenced-based recommendations for the optimal strategy of CINV control in this setting. The chapter provides an overview of CINV in patients undergoing high-dose chemotherapy regimens, with a focus on challenges and unmet needs in this special population. It also provides an overview of the results with modern antiemetics in this setting. Finally, current treatment guidelines are also discussed along with suggestions for future investigations.
