International Journal of Hematology

, Volume 105, Issue 4, pp 478–484 | Cite as

Palonosetron, aprepitant, and dexamethasone for prevention of nausea and vomiting after high-dose melphalan in autologous transplantation for multiple myeloma: A phase II study

  • Atsushi Isoda
  • Rie Saito
  • Fuminori Komatsu
  • Yuki Negishi
  • Noriyasu Oosawa
  • Tetsuya Ishikawa
  • Yuri Miyazawa
  • Morio Matsumoto
  • Morio Sawamura
  • Akihiro Manaka
Original Article


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/m2 on days 1–2) before ASCT (on day 4). Intravenous palonosetron (0.75 mg on day 1), oral aprepitant (125 mg on day 1; 80 mg on days 2–4), and intravenous dexamethasone (6.6 mg on days 1–4) were administered for prevention of CINV. Complete response (no emesis and no rescue antiemetic) and complete control (no emesis, no rescue antiemetic, and no more than mild nausea) rates were 75 and 68% during the overall phase (0–120 h), while they were 88 and 86% in the acute phase (0–48 h), 75 and 68% in the delayed phase (48–120 h), and 67 and 59% in the extended phase (120–168 h), respectively. There were no serious adverse events related to the antiemetic therapy. In conclusion, the three-antiemetic regimen consisting of palonosetron, aprepitant, and dexamethasone was safe and effective for controlling CINV due to high-dose melphalan treatment, especially during the delayed phase.


Multiple myeloma High-dose melphalan Nausea Palonosetron Aprepitant 



The authors would like to thank Drs. Momoko Mawatari, Akio Saito, Akinori Yuzuriha, Naru Sato, and Hiroko Koya for their contributions to patient care and data collection.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371:895–905.CrossRefPubMedGoogle Scholar
  2. 2.
    Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, et al. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015;16:1617–29.CrossRefPubMedGoogle Scholar
  3. 3.
    Cunningham D, Paz-Ares L, Milan S, Powles R, Nicolson M, Hickish T, et al. High-dose melphalan and autologous bone marrow transplantation as consolidation in previously untreated myeloma. J Clin Oncol. 1994;12:759–63.CrossRefPubMedGoogle Scholar
  4. 4.
    Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F, et al. Comparison of 200 mg/m2 melphalan and 8 Gy total body irradiation plus 140 mg/m2 melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood. 2002;99:731–5.CrossRefPubMedGoogle Scholar
  5. 5.
    Trigg ME, Inverso DM. Nausea and vomiting with high-dose chemotherapy and stem cell rescue therapy: a review of antiemetic regimens. Bone Marrow Transplant. 2008;42:501–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Maemondo M, Masuda N, Sekine I, Kubota K, Segawa Y, Shibuya M, et al. A phase II study of palonosetron combined with dexamethasone to prevent nausea and vomiting induced by highly emetogenic chemotherapy. Ann Oncol. 2009;20:1860–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Wong EH, Clark R, Leung E, Loury D, Bonhaus DW, Jakeman L, et al. The interaction of RS 25259-197, a potent and selective antagonist, with 5-HT3 receptors, in vitro. Br J Pharmacol. 1995;114:851–9.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Schwartzberg L, Barbour SY, Morrow GR, Ballinari G, Thorn MD, Cox D. Pooled analysis of phase III clinical studies of palonosetron versus ondansetron, dolasetron, and granisetron in the prevention of chemotherapy-induced nausea and vomiting (CINV). Support Care Cancer. 2014;22:469–77.CrossRefPubMedGoogle Scholar
  9. 9.
    Segawa Y, Aogi K, Inoue K, Sano M, Sekine I, Tokuda Y, et al. A phase II dose-ranging study of palonosetron in Japanese patients receiving moderately emetogenic chemotherapy, including anthracycline and cyclophosphamide-based chemotherapy. Ann Oncol. 2009;20:1874–80.CrossRefPubMedGoogle Scholar
  10. 10.
    Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Ma GJ, Eldridge K, Hipple A, et al. Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting: results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer. 2003;97:3090–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, De Wit R, et al. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin—the aprepitant protocol 052 study G. J Clin Oncol. 2003;21:4112–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer PC, Somerfield MR, et al. Antiemetics: American society of clinical oncology clinical practice guideline update. J Clin Oncol. 2011;29:4189–98.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Deauna-Limayo D, Aljitawi OS, Ganguly S, Abhyankar S, Wick JA, McGuirk JP. Combined use of multiday palonosetron with aprepitant and low-dose dexamethasone in prevention of nausea and emesis among patients with multiple myeloma and lymphoma undergoing autologous hematopoietic stem cell transplant: a pilot study. J Oncol Pharm Pract. 2013;20:263–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Jordan K, Jahn F, Jahn P, Behlendorf T, Stein A, Ruessel J, et al. The NK-1 receptor-antagonist aprepitant in high-dose chemotherapy (high-dose melphalan and high-dose T-ICE: paclitaxel, ifosfamide, carboplatin, etoposide): efficacy and safety of a triple antiemetic combination. Bone Marrow Transplant. 2011;46:784–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Bechtel T, McBride A, Crawford B, Bullington S, Hofmeister CC, Benson DM, et al. Aprepitant for the control of delayed nausea and vomiting associated with the use of high-dose melphalan for autologous peripheral blood stem cell transplants in patients with multiple myeloma: a phase II study. Support Care Cancer. 2014;22:2911–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Schmitt T, Goldschmidt H, Neben K, Freiberger A, Husing J, Gronkowski M, 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 III trial. J Clin Oncol. 2014;32:3413–20.CrossRefPubMedGoogle Scholar
  17. 17.
    Musso M, Scalone R, Crescimanno A, Bonanno V, Polizzi V, Porretto F, et al. Palonosetron and dexamethasone for prevention of nausea and vomiting in patients receiving high-dose chemotherapy with auto-SCT. Bone Marrow Transplant. 2010;45:123–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Giralt SA, Mangan KF, Maziarz RT, Bubalo JS, Beveridge R, Hurd DD, et al. Three palonosetron regimens to prevent CINV in myeloma patients receiving multiple-day high-dose melphalan and hematopoietic stem cell transplantation. Ann Oncol. 2011;22:939–46.CrossRefPubMedGoogle Scholar
  19. 19.
    Ikari Y, Ogata K, Nakashima Y, Sato E, Masaki M, Katsuya H, et al. Safety and pharmacokinetic evaluation of repeated intravenous administration of palonosetron 0.75 mg in patients receiving highly or moderately emetogenic chemotherapy. Support Care Cancer. 2014;22:1959–64.CrossRefPubMedGoogle Scholar
  20. 20.
    Fujii H, Okamoto S, Kodera Y, Ogura M, Tanimoto M, Hirano M, et al. A clinical study of L-PAM injection as the pre-conditioning for hematopoietic stem cell transplantation in patients with hematological malignancies. Transplant Now. 2001;14:673–84 (article in Japanese).Google Scholar
  21. 21.
    Roila F, Boschetti E, Tonato M, Basurto C, Bracarda S, Picciafuoco M, et al. Predictive factors of delayed emesis in cisplatin-treated patients and antiemetic activity and tolerability of metoclopramide or dexamethasone. A randomized single-blind study. Am J Clin Oncol. 1991;14:238–42.CrossRefPubMedGoogle Scholar
  22. 22.
    Du Bois A, Meerpohl HG, Kommoss FGM, Pfleiderer A, Vach W, Fenzl E. Course, patterns, and risk-factors for chemotherapy-induced emesis in cisplatin-pretreated patients: a study with ondansetron. Eur J Cancer. 1992;28:450–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Sekine I, Segawa Y, Kubota K, Saeki T. Risk factors of chemotherapy-induced nausea and vomiting: index for personalized antiemetic prophylaxis. Cancer Sci. 2013;104:711–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Razavi D, Delvaux N, Farvacques C, De Brier F, Van Heer C, Kaufman L, et al. Prevention of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy: a double-blind, placebo-controlled study assessing the usefulness of alprazolam. J Clin Oncol. 1993;11:1384–90.CrossRefPubMedGoogle Scholar
  25. 25.
    Malik IA, Khan WA, Qazilbash M, Ata E, Butt A, Khan MA. Clinical efficacy of lorazepam in prophylaxis of anticipatory, acute, and delayed nausea and vomiting induced by high doses of cisplatin. A prospective randomized trial. Am J Clin Oncol. 1995;18:170–5.CrossRefPubMedGoogle Scholar
  26. 26.
    Navari RM, Einhorn LH, Loehrer PJ, Passik SD, Vinson J, McClean J, et al. A phase II trial of olanzapine, dexamethasone, and palonosetron for the prevention of chemotherapy-induced nausea and vomiting: a Hoosier oncology group study. Support Care Cancer. 2007;15:1285–91.CrossRefPubMedGoogle Scholar
  27. 27.
    Kamen C, Tejani MA, Chandwani K, Janelsins M, Peoples AR, Roscoe JA, et al. Anticipatory nausea and vomiting due to chemotherapy. Eur J Pharmacol. 2014;722:172–9.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2016

Authors and Affiliations

  • Atsushi Isoda
    • 1
  • Rie Saito
    • 2
  • Fuminori Komatsu
    • 2
  • Yuki Negishi
    • 2
  • Noriyasu Oosawa
    • 2
  • Tetsuya Ishikawa
    • 1
  • Yuri Miyazawa
    • 1
  • Morio Matsumoto
    • 1
  • Morio Sawamura
    • 3
  • Akihiro Manaka
    • 2
    • 4
  1. 1.Department of HematologyNational Hospital Organization Shibukawa Medical CenterShibukawaJapan
  2. 2.Department of PharmacyNational Hospital Organization Shibukawa Medical CenterShibukawaJapan
  3. 3.Department of Clinical ResearchNational Hospital Organization Shibukawa Medical CenterShibukawaJapan
  4. 4.Department of Clinical Laboratory MedicineGunma University Graduate School of MedicineMaebashiJapan

Personalised recommendations