Original StudyOlanzapine Reduces Chemotherapy-induced Nausea and Vomiting Compared With Aprepitant in Myeloma Patients Receiving High-dose Melphalan Before Stem Cell Transplantation: A Retrospective Study
Introduction
High-dose melphalan (HDM) is routinely used as a preparative regimen before autologous stem cell transplantation (HSCT) for patients with multiple myeloma and other hematologic malignancies. Melphalan is highly emetogenic and can cause acute and delayed chemotherapy-induced nausea and vomiting (CINV) in ≤ 80% to 100% of patients undergoing HSCT.1 Olanzapine, an antipsychotic agent, has been shown to control breakthrough CINV in patients with solid tumors. Consensus guidelines have recommended olanzapine or aprepitant with a serotonin receptor antagonist (5HT3) and corticosteroid for the prevention of CINV in patients who receive highly emetogenic chemotherapy; however, the consensus guidelines have not addressed CINV prevention for patients receiving high-dose conditioning regimens before stem cell transplantation.2, 3 (A summary of the more recent updates can be found in the presentation of the Multinational Association of Supportive Care in Cancer [MASCC]/European Society for Medical Oncology Antiemetic Guideline 2013. The most recent update can be found at the MASCC website: MASCC Antiemetic Guidelines.) In our experience, prevention of acute and delayed CINV after HDM administration was suboptimal with an aprepitant regimen. Owing to favorable results reported in the nontransplantation setting, we changed our CINV prevention from an aprepitant-based regimen to an olanzapine-based regimen for patients receiving HDM before stem cell transplantation. We performed a retrospective study to assess the safety and efficacy of an olanzapine-based regimen during transplantation and compare our results to those of patients who had recently received a standard aprepitant regimen.
Section snippets
Patients and Methods
The Northwestern Memorial Hospital electronic database was used for data extraction for the present retrospective study. Consecutive hospital inpatients who had received melphalan 200 mg/m2 given as a single undiluted 20-minute intravenous (IV) infusion on day −1 before autografting and treated from January 1, 2015 through January 1, 2016 were included in the present study. The aprepitant-based regimen was given as follows: IV ondansetron 16 mg, oral aprepitant 125 mg, and methylprednisolone
Results
The demographic data are listed in Table 1. A total of 117 patients were identified who had been treated with aprepitant (n = 54), olanzapine (n = 43), or fosaprepitant (n = 20). No significant differences were found in age, gender, melphalan dose according to milligrams/kilogram or milligrams/square meters, ondansetron treatment days, or interval to stem cell engraftment among the 3 study arms. Olanzapine was administered for a median of 5 days (range, 2-15 days). Differences in the length of
Discussion
The effects of CINV after HDM therapy can be debilitating, causing dehydration, loss of appetite and nutrition, weight and muscle loss, diminished quality of life, and delayed hospital discharge. Prevention of acute and delayed CINV remains challenging. A 3-drug regimen with a neurokinin-1 inhibitor, 5HT3 inhibitor, and corticosteroid for HDM has been shown to improve CINV control compared with therapy with a 5HT3 antagonist plus corticosteroid alone. However, most transplant patients continue
Conclusion
Olanzapine appears to improve acute and delayed CINV control better than does an aprepitant-based regimen for HSCT recipients treated with HDM. Prevention of delayed CINV, especially that developing > 5 days after HDM administration, remains problematic.
Disclosure
The authors have stated that they have no conflicts of interest.
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Randomized, Placebo-Controlled, Phase III Trial of Fosaprepitant, Ondansetron, Dexamethasone (FOND) Versus FOND Plus Olanzapine (FOND-O) for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients with Hematologic Malignancies Receiving Highly Emetogenic Chemotherapy and Hematopoietic Cell Transplantation Regimens: The FOND-O Trial
2018, Biology of Blood and Marrow TransplantationCitation Excerpt :Our study design evaluating VAS scores for 5 days after the last day of chemotherapy administration has routinely been performed in previous CINV study designs. A recent retrospective study that assessed olanzapine efficacy in patients receiving high-dose melphalan demonstrated benefit > 5 days post-transplantation due to improved delayed CINV rates [17]. Patient-reported nausea has consistently demonstrated a negative impact on patient quality of life [27,28] and is a commonly expressed fear of chemotherapy [29].
Chemotherapy-induced Nausea and Vomiting Prophylaxis in High-dose Melphalan and Autologous Stem Cell Transplantation
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