Original Study
Olanzapine Reduces Chemotherapy-induced Nausea and Vomiting Compared With Aprepitant in Myeloma Patients Receiving High-dose Melphalan Before Stem Cell Transplantation: A Retrospective Study

https://doi.org/10.1016/j.clml.2017.06.012Get rights and content

Abstract

Introduction

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.

Patients and Methods

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.

Results

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.

Conclusion

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.

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.

References (17)

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    Citation 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].

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