Aprepitant for the Prevention of Chemotherapy-Induced Nausea, Vomiting in Multiple Myeloma

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The addition of aprepitant to granisetron and dexamethasone resulted resulted in less chemotherapy-induced nausea and vomiting.
The addition of aprepitant to granisetron and dexamethasone resulted resulted in less chemotherapy-induced nausea and vomiting.

According to a recent study published in the Journal of Clinical Oncology, the addition of aprepitant to granisetron and dexamethasone resulted in significantly less chemotherapy-induced nausea and vomiting (CINV) and improved quality of life in patients receiving high-dose melphalan in autologous stem-cell transplantation (ASCT) for the treatment of multiple myeloma.

In the randomized, placebo-controlled phase 3 study, researchers from Heidelberg University Hospital in Heidelberg, Germany, sought to determine the optimal regimen to prevent CINV for patients receiving high-dose melphalan and ASCT.1

Patients with multiple myeloma were given one of two regimens: (1) aprepitant 125 mg orally on day 1 and 80 mg orally on days 2 through 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 and 3, or (2) 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 and 3.

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Of the 181 patients in each treatment arm, 58% of patients receiving the combination with aprepitant achieved a complete response, defined as no emesis and no rescue therapy within 120 hours after treatment with melphalan, compared with 41% of patients receiving the regimen with placebo (odds ratio [OR], 1.92; 95 CI, 1.23-3.00; P=0.0042).

Furthermore, 94% of patients treated with aprepitant had no major nausea versus 88% treated with placebo (OR, 2.37; 95% CI, 1.09-5.15; P=0.026), and 78% of patients treated with aprepitant had no emesis versus 65% treated with placebo (OR, 1.99; 95% CI, 1.25-3.18; P=0.0036) within 120 hours of melphalan treatment.

In order to measure quality of life, researchers surveyed patients using a modified Functional Living Index–Emesis questionnaire. Of 356 patients surveyed, 74% of patients receiving the regimen containing aprepitant had reported no change to daily life compared with 59% of patients receiving placebo (P=0.004).1

The American Society of Clinical Oncology (ASCO) recommends the combination of a 5-HT3 antagonist, such as granisetron, ondansetron, and palonosetron, and dexamethasone for the prevention of CINV in patients receiving high-dose chemotherapy and ASCT; however, the optimal regimen for prophylaxis has yet to be determined.1,2 ASCO guidelines recommend the consideration of aprepitant in addition to a 5-HT3 antagonist and dexamethasone, but acknowledge that there is limited evidence to support its use in patients receiving stem-cell transplantation.

Aprepitant is an oral substance P and neurokinin 1 (NK1) receptor antagonist approved by the U.S. Food and Drug Administration for the prevention of CINV in combination with a 5-HT3 antagonist and a corticosteroid, like dexamethasone.3 The recommended dose is 125 mg orally 1 hour prior to chemotherapy on day 1 and 80 mg orally once daily on days 2 and 3. Fosaprepitant dimeglumine, the intravenous formulation, can be substituted for aprepitant on day 1.3

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Because this study demonstrated a high rate of emesis in both treatment arms, palonosetron may be considered as an alternative to granisetron as it provides superior control of delayed emesis compared with first-generation 5-HT3 antagonists; however, no studies have shown whether this effect holds true when combined with an NK1 antagonist.4,5

The study results showed that the aprepitant-containing regimen significantly reduced the incidence of acute and delayed nausea and emesis compared with placebo, and therefore, the use of aprepitant in addition to a 5-HT3 antagonist and dexamethasone for patients with multiple myeloma receiving high-dose chemotherapy and ASCT should be heavily considered.

References

  1. Schmitt T, Goldschmidt H, Neben K, et al. Aprepitant, granisetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting after high-dose melphalan in autologous transplantation for multiple myeloma: results of a randomized, placebo-controlled phase 3 trial. J Clin Oncol. 2014 Sep 15. [Epub ahead of print] doi: 10.1200/JCO.2013.55.0095.
  2. Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2011;29(31):4189-4198.
  3. Emend [package insert]. Whitehouse Station, NJ: Merck & Co., Inc. https://www.merck.com/product/usa/pi_circulars/e/emend/emend_pi.pdf
  4. Saito M, Aogi K, Sekine I, et al. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomized, comparative phase III trial. Lancet Oncol. 2009;10(2):115-124.
  5. Aapro MS, Grunberg SM, Manikhas GM, et al. A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol. 2006;17(9):1441-1449.

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