aprepitant and Multiple-Myeloma

High-dose melphalan (HDMel) is the most common conditioning chemotherapy regimen for autologous stem cell transplantation (SCT) in patients affected by multiple myeloma (MM). No consensus exists for the emetogenicity or prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in this regimen.. Data on the incidence and efficacy/safety of CINV prophylaxis among patients affected by MM undergoing autologous SCT with the HDMel regimen was extracted from electronic databases and analyzed.. Eleven studies involving multiple CINV prophylaxis regimens were identified and included. No consensus on HDMel emetogenicity was reached, but most studies summarized the emetogenicity as moderate-high risk. An aprepitant-based three-drug regimen (aprepitant + serotonin receptor antagonist (5HT3RA) + dexamethasone) showed better efficacy than a two-drug regimen (5HT3RA + dexamethasone) for CINV prevention without increasing the frequency in adverse events.. The aprepitant-based three-drug regimen should be the regimen of choice for CINV prophylaxis for MM patients undergoing autologous SCT with HDMel conditioning.

Topics: Adult; Antiemetics; Antineoplastic Agents, Alkylating; Aprepitant; Dexamethasone; Female; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Male; Melphalan; Multiple Myeloma; Nausea; Quality of Life; Serotonin Antagonists; Transplantation Conditioning; Transplantation, Autologous; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a significant side effect in multiple myeloma (MM) patients receiving high-dose melphalan treatment followed by autologous stem cell transplantation (ASCT). We evaluated the efficacy and safety of a triple antiemetic combination of palonosetron, aprepitant, and low-dose dexamethasone in 24 MM patients who received melphalan conditioning (100 mg/m

Topics: Adult; Aged; Antiemetics; Aprepitant; Dexamethasone; Drug Therapy, Combination; Humans; Isoquinolines; Melphalan; Middle Aged; Morpholines; Multiple Myeloma; Myeloablative Agonists; Palonosetron; Postoperative Nausea and Vomiting; Quinuclidines; Transplantation, Autologous; Treatment Outcome

Chemotherapy-induced nausea/vomiting (CINV) is a major problem for patients treated with high-dose chemotherapy (HDCT) conditioning before stem cell transplantation (SCT), both during chemotherapy and afterwards (delayed nausea/vomiting). The standard of care (5-HT3 antagonist and dexamethasone) appears to be ineffective against delayed nausea and vomiting. The objective of this study was to compare standard antiemetic treatment with standard treatment plus prolonged treatment with aprepitant (Emend®) until 7 days after the end of chemotherapy in patients treated with HDCT before autologous SCT. Ninety-six patients were randomized to the experiment (EXP) group receiving Emend in addition to standard antiemetics or to the control (CTR) group receiving placebo. Emend or placebo treatment started 1 h before the first HDCT dose for SCT and ended 7 days after HDCT. Thirty-eight patients in the EXP group experienced complete response (no vomiting) compared to 16 patients in the CTR group. There was a significant difference between the EXP (0.63 ± 2.71) and the CTR (3.72 ± 4.91) group during 10 days after the end of HDCT (p = 0.001) with regard to the number of vomiting episodes. No difference with regard to days of nausea or in the use of antiemetic rescue was noted between the groups. We conclude that standard antiemetic treatment can be improved by addition of aprepitant continued for 7 days after the end of chemotherapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Dexamethasone; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lymphoma; Male; Middle Aged; Morpholines; Multiple Myeloma; Nausea; Serotonin 5-HT3 Receptor Antagonists; Stem Cell Transplantation; Treatment Outcome; Vomiting

The aim of this study is to evaluate the efficacy of aprepitant as part of the antiemetic regimen for high-dose melphalan conditioning in multiple myeloma patients.. This is a prospective, single-arm study.. The study was conducted at an Academic Medical Facility.. Twenty-six patients receiving high-dose melphalan with autologous stem cell support were included in this study.. Eligible patients were >18 years with a diagnosis of MM undergoing high-dose melphalan followed by autologous peripheral blood stem cell transplantation (PBSCT). All patients had serum aminotransferases and total bilirubin less than 2× upper limit of normal. Treatment consisted of aprepitant 125 mg orally on day 1, followed by 80 mg orally 24 and 48 h after the initial dose; ondansetron 16 mg orally day 1; dexamethasone 12 mg orally day 1, and 8 mg orally days 2-4 with breakthrough medications as needed.. Patients were evaluated for the frequency of emetic episodes, the need for breakthrough antiemetic medication, and the mean nausea score in 24-h increments beginning 24 h after chemotherapy and continuing until 120 h. Nausea score was determined using a linear analog scale (0-10). Complete response (CR) was defined as no more than one (1) emetic episode during the evaluation period. A total of 26 patients (17 male, 9 female) were enrolled in the study. Of these, 25 (96 %) were complete responders and 24 (92 %) had no documented emetic episodes during the study period. One patient (4 %) had 1 emetic episode and one patient (4 %) had 2 emetic episodes. Some degree of nausea was reported by 23/26 patients, and the mean nausea score for the entire group over the study period was 0.7 (range 0-10).. Addition of aprepitant to standard antiemetics resulted in low rates of delayed nausea/vomiting associated with high-dose melphalan and PBSCT, and has now become standard practice in this patient population at our institution.

Topics: Antiemetics; Aprepitant; Female; Humans; Male; Melphalan; Middle Aged; Morpholines; Multiple Myeloma; Nausea; Peripheral Blood Stem Cell Transplantation; Prospective Studies; Transplantation Conditioning; Vomiting

The optimal regimen to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing high-dose chemotherapy and autologous stem-cell transplantation (ASCT) is unclear. To evaluate the effect of aprepitant in addition to a standard regimen, we conducted this randomized, placebo-controlled phase III trial.. Patients with multiple myeloma were randomly assigned at a one-to-one ratio to receive either aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 to 4), granisetron (2 mg orally on days 1 to 4), and dexamethasone (4 mg orally on day 1 and 2 mg orally on days 2 to 3) or matching placebo, granisetron (2 mg orally on days 1 to 4), and dexamethasone (8 mg orally on day 1 and 4 mg orally on days 2 to 3). Melphalan 100 mg/m(2) was administered intravenously on days 1 to 2. ASCT was performed on day 4. The primary end point (complete response) was defined as no emesis and no rescue therapy within 120 hours of melphalan administration. Quality of life was assessed by modified Functional Living Index-Emesis (FLIE) questionnaire on days -1 and 6.. Overall, 362 patients were available for the efficacy analysis (181 in each treatment arm). Significantly more patients receiving aprepitant reached the primary end point (58% v 41%; odds ratio [OR], 1.92; 95% CI, 1.23 to 3.00; P = .0042). Absence of major nausea (94% v 88%; OR, 2.37; 95% CI, 1.09 to 5.15; P = .026) and emesis (78% v 65%; OR, 1.99; 95% CI, 1.25 to 3.18; P = .0036) within 120 hours was increased by aprepitant. Mean total FLIE score (± standard deviation) was 114 ± 18 for aprepitant and 106 ± 26 for placebo (P < .001).. The addition of aprepitant resulted in significantly less CINV and had a positive effect on quality of life.

Topics: Aprepitant; Dexamethasone; Double-Blind Method; Granisetron; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Morpholines; Multiple Myeloma; Nausea; Prospective Studies; Quality of Life; Transplantation, Autologous; Vomiting

The objective of this investigation was to assess the effect of aprepitant on the pharmacokinetics of high-dose melphalan used as conditioning therapy before blood stem cell transplantation in multiple myeloma.. Aprepitant (125 mg) or placebo was administered 1 h before melphalan therapy (1 h infusion of 100 mg m⁻²). Eleven plasma samples were obtained over 8 h and melphalan was quantified using an LC/MS/MS method. Standard pharmacokinetic parameters were calculated and nonparametric testing was applied to assess the differences between aprepitant and placebo treatment.. Twenty patients received placebo and 10 patients aprepitant treatment. There were no differences observed for C(max) at the end of melphalan infusion (placebo 3431 ± 608 ng ml⁻¹ vs. aprepitant 3269 ± 660 ng ml⁻¹). In addition, AUC and terminal elimination half-life were not changed by aprepitant. Total clearance of melphalan was 304 ± 58 ml min⁻¹ m⁻² (placebo) which was not influenced by aprepitant (288 ± 78 ml min⁻¹ m⁻²).. The administration of the NK₁ receptor antagonist aprepitant 1 h before a high-dose chemotherapy does not influence the exposure and the elimination of melphalan. Therefore, oral administration of 125 mg aprepitant 1 h before melphalan infusion does not alter the disposition of intravenously administered melphalan.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents, Alkylating; Aprepitant; Double-Blind Method; Drug Administration Schedule; Drug Interactions; Female; Hematopoietic Stem Cell Transplantation; Humans; Infusions, Intravenous; Male; Melphalan; Middle Aged; Morpholines; Multiple Myeloma; Neurokinin-1 Receptor Antagonists; Prospective Studies; Transplantation Conditioning

Acute and delayed chemotherapy-induced nausea and vomiting (CINV) occurs in most patients who receive high-dose melphalan and significantly affects patients' quality of life during autologous stem cell transplantation. Faced with unsatisfactory results using an aprepitant-based regimen, an olanzapine-based regimen was initiated, with the hope of improving the incidence of acute and delayed CINV. A retrospective study was conducted to compare the effectiveness of olanzapine- versus aprepitant-based regimens for CINV prevention in adult hematopoietic stem cell recipients who received high-dose melphalan.. We compared olanzapine (n = 43) to aprepitant (n = 54) and fosaprepitant (n = 20). Olanzapine was given orally at 5 mg twice daily for 5 days, aprepitant was given at 125 mg on day -1 and 80 mg on days 0 and 1, and fosaprepitant was given at 150 mg on day -1. The dose of 2 concomitant drugs (dexamethasone and 5-hydroxytryptamine type 3 receptor antagonist) was similar in the 2 groups. Nausea prevention was the primary endpoint. A complete response using a composite index of no emesis and no use of rescue medications was the secondary endpoint.. The results showed that olanzapine significantly reduced the number of patients who experienced acute (P < .0001) or delayed (P < .004) nausea and significantly reduced the use of rescue medications for acute-onset (P < .0046) and delayed-onset (P < .0001) CINV compared with aprepitant.. Compared with fosaprepitant, olanzapine reduced the number of patients with acute (P < .0318) and delayed (P < .1519) nausea and reduced the need for rescue medications for acute-onset (P < .0643) and delayed-onset (P < .0024) CINV.

Topics: Adult; Aged; Algorithms; Antiemetics; Aprepitant; Benzodiazepines; Disease Management; Female; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Male; Melphalan; Middle Aged; Morpholines; Multiple Myeloma; Myeloablative Agonists; Nausea; Olanzapine; Transplantation Conditioning; Treatment Outcome; Vomiting

To evaluate the clinical and cost benefits of the administration of aprepitant for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) during high-dose chemotherapy (HDCT).. We retrospectively reviewed the charts of patients who received HDCT at our institution between January 2009 and December 2013. Cost-effectiveness was analyzed using direct medical costs.. We identified a total of 38 patients (27 with non-Hodgkin lymphoma and 11 with multiple myeloma). Thirteen patients received aprepitant and granisetron (aprepitant group) for CINV prophylaxis, whereas 25 patients received granisetron only (non-aprepitant group). The incidence of severe nausea (≥grade 3) was significantly lower in the aprepitant group than in the non-aprepitant group (p = 0.039). The total mean cost per patient during hospitalization, excluding the cost of HDCT and transplantation, was USD 10,941.8 in the aprepitant group and USD 14,577.2 in the non-aprepitant group (p = 0.041). This cost benefit reflected reductions in the costs of hospitalization, transfusion, and infection treatment.. Our data indicated that the addition of aprepitant for CINV prophylaxis during HDCT reduced the incidence of severe nausea and might also provide economic benefit in the overall management of HDCT prior to autologous peripheral blood stem cell transplantation.

Topics: Adult; Aged; Antineoplastic Agents; Aprepitant; Cost-Benefit Analysis; Female; Granisetron; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Morpholines; Multiple Myeloma; Nausea; Peripheral Blood Stem Cell Transplantation; Retrospective Studies; Vomiting

The current standard for prevention of chemotherapy-induced nausea/vomiting in autologous stem cell transplant only achieves 4-20% emetic control.. To assess emetic responses to multiday palonosetron, aprepitant, and low-dose dexamethasone among patients with myeloma and lymphoma undergoing autologous hematopoietic stem cell transplant.. Oral aprepitant 125/80/80 mg was administered with intravenous dexamethasone 4 mg and palonosetron 0.25 mg on days -3, -2, -1 for multiple myeloma and days -7 through -3 for lymphoma. Palonosetron was repeated day +3 in both groups.. A total of 20 patients were enrolled and 18 analyzed. None experienced emetic failure with complete control achieved in 78, 33, and 17% in the acute, delayed, and extended phases, respectively. Nausea occurred in 78% although not significant in 61%, with median Nausea Visual Score of 4.5. Quality of life correlated with emetic and nausea control. Eight patients developed grade 2-3 nonhematologic toxicities with only one event attributed to the study medications.. This triplet regimen was feasible with acceptable safety profile in the autologous hematopoietic stem cell transplant setting. Emetic control was best achieved in the acute phase. Lesser degree of emetic and nausea control in the delayed and extended phases impacted quality of life. Our results warrant further evaluation in a larger autologous hematopoietic stem cell transplant population.

Topics: Adult; Aged; Antiemetics; Aprepitant; Dexamethasone; Female; Hematopoietic Stem Cell Transplantation; Humans; Isoquinolines; Lymphoma; Male; Middle Aged; Morpholines; Multiple Myeloma; Nausea; Palonosetron; Pilot Projects; Quality of Life; Quinuclidines; Transplantation, Autologous; Vomiting