Antiemesis

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search

Adapted from the NCCN[1], ASCO[2] and MASCC/ESMO[3]

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ASCO

ESMO

MASCC/ESMO

NCCN

Emetic risk of chemotherapy, immunotherapy, TKIs and other agents

Hint: You can sort the table by clicking on the boxes containing arrows at the top of each column.
All drugs are IV route unless otherwise specified.

NCCN, ASCO and MASCC categories of emetic risk in the absence of prophylaxis:

  • High: >90% frequency of emesis (HEC)
  • Moderate: 30-90% frequency of emesis (MEC)
  • Low: 10-30% frequency of emesis
  • Minimal: less than 10% frequency of emesis

ASCO guidelines say that in cases of combination chemotherapy regimens, patients should be given antiemetics that are recommended for the individual medication with the highest emetic risk. The exception is with anthracycline and Cyclophosphamide (Cytoxan) combinations as described below.

Drug NCCN emetogenic potential (2021) ASCO emetogenic potential

(2020)

MASCC/ESMO emetogenic potential (2019) Comment
Trastuzumab emtansine (Kadcyla) Low Low Low
Anthracycline (see differences between NCCN & ASCO) & Cyclophosphamide (Cytoxan) combination chemotherapy High (Doxorubicin (Adriamycin) or Epirubicin (Ellence) with Cyclophosphamide (Cytoxan)) High (Daunorubicin (Cerubidine), Doxorubicin (Adriamycin), Epirubicin (Ellence), or Idarubicin (Idamycin) with Cyclophosphamide (Cytoxan)) High MASCC comment - in patients with breast cancer
Aldesleukin (Proleukin) Moderate: >12 to 15 million international units/m2
Low: ≤12 million international units/m2
Alemtuzumab (Campath) Minimal Moderate Moderate
Altretamine (Hexalen) or Hexamethylmelamine (oral) Moderate/High Moderate/High NCCN and ASCO did not further delineate between degrees of emetic potential
Amifostine (Ethyol) Moderate: >300 mg/m2
Low: ≤300 mg/m2
Arsenic trioxide (Trisenox) Low Moderate
Asparaginase (Elspar) Minimal
Atezolizumab (Tecentriq) Minimal Minimal
Axitinib (Inlyta) (oral) Minimal/Low Minimal/Low Low
Azacitidine (Vidaza) Moderate Moderate Moderate
Bendamustine Moderate Moderate Moderate
Belinostat (Beleodaq) Low
Bevacizumab (Avastin) Minimal Minimal Minimal
Bexarotene (Targretin) (oral) Low/Minimal NCCN did not further delineate between degrees of emetic potential
Bleomycin (Blenoxane) Minimal Minimal Minimal
Blinatumomab (Blincyto) Low Low
Bortezomib (Velcade) Minimal Low Low
Bosutinib (Bosulif) (oral) Low/Minimal Moderate Moderate
Brentuximab vedotin (Adcetris) Low Low
Busulfan (Myleran) High/Moderate: at least 4 mg/day
Low/Minimal: less than 4 mg/day
Minimal Minimal
Busulfan (Myleran) (oral) High/Moderate: at least 4 mg/day
Low/Minimal: less than 4 mg/day
NCCN did not further delineate between degrees of emetic potential
Cabazitaxel (Jevtana) Low Low Low
Cabozantinib (Cometriq) (oral) Low/Minimal Moderate
Capecitabine (Xeloda) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Carboplatin (Paraplatin) High: AUC 4 or more

Moderate: AUC less than 4

Moderate (but recommended triplet combination of NK1, 5-HT3, and Dex if AUC 4 or more) Moderate (but recommended triplet combination of NK1, 5-HT3, and dexamethasone) MASCC/ESMO did not subclassify based on dose
Carfilzomib (Kyprolis) Low Low
Carmustine (BCNU) High: >250 mg/m2
Moderate: ≤250 mg/m2
High High ASCO and MASCC/ESMO did not subclassify based on dose
Catumaxomab (Removab) Low Low
Cetuximab (Erbitux) Minimal Minimal Low
Ceritinib (Zykadia) Moderate
Chlorambucil (Leukeran) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Cisplatin (Platinol) High High High Some only consider emetogenic potential high when dose 70 mg/m2 or more
Cladribine (Leustatin) Minimal Minimal Minimal
Clofarabine (Clolar) Moderate Moderate Moderate
Crizotinib (Xalkori) (oral) High/Moderate Moderate Moderate
Cyclophosphamide (Cytoxan) High: greater than 1500 mg/m2 or when given with certain anthracyclines
Moderate: up to and including 1500 mg/m2
High: 1500 mg/m2 or more, or when given with anthracyclines
Moderate: less than 1500 mg/m2
High: > 1500 mg/m2 or when combined with anthracyclines (in breast cancer patients)

Moderate: < 1500 mg/m2

Cyclophosphamide (Cytoxan) (oral) High/Moderate: 100 mg/m2/day or more
Low/Minimal: less than 100 mg/m2/day
Moderate Moderate NCCN did not further delineate between degrees of emetic potential
Cytarabine (Ara-C) Moderate: >200 mg/m2
Low: 100 to 200 mg/m2
Minimal: less than 100 mg/m2
Moderate: >1000 mg/m2
Low: ≤1000 mg/m2
Moderate: > 1000 mg/m2

Low: < 1000 mg/m2

Dabrafenib (Tafinlar) (oral) Low/Minimal Low
Dacarbazine (DTIC) High High High
Daratumumab (Darzalex) Minimal
Dactinomycin (Cosmegen) Moderate High
Dasatinib (Sprycel) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Daunorubicin (Cerubidine) Moderate High when given with Cyclophosphamide (Cytoxan)
Moderate when used alone
High: when given with combined with cyclophosphamide (in breast cancer patients)

Moderate: when used alone

Decitabine (Dacogen) Minimal
Denileukin diftitox (Ontak) Minimal
Dexrazoxane (Zinecard) Minimal
Docetaxel (Taxotere) Low Low Low
Doxorubicin (Adriamycin) High: 60 mg/m2 or more, or when given at any dose with Cyclophosphamide (Cytoxan)
Moderate: less than 60 mg/m2
High when given with Cyclophosphamide (Cytoxan)
Moderate when used alone
High: when given with combined with cyclophosphamide (in breast cancer patients)

Moderate: when used alone

Pegylated liposomal doxorubicin (Doxil) Low Low Low
Epirubicin (Ellence) High: >90 mg/m2 or when given at any dose with Cyclophosphamide (Cytoxan)
Moderate: ≤90 mg/m2
High when given with Cyclophosphamide (Cytoxan)
Moderate when used alone
High: when combined with cyclophosphamide (in breast cancer patients)

Moderate: when used alone

Eribulin (Halaven) Low Low
Erlotinib (Tarceva) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Estramustine (Emcyt) (oral) High/Moderate NCCN did not further delineate between degrees of emetic potential
Etoposide (Vepesid) Low Low Low
Etoposide (Vepesid) (oral) High/Moderate Low NCCN did not further delineate between degrees of emetic potential
Everolimus (Afinitor) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Floxuridine (FUDR) Low
Fludarabine (Fludara) Minimal Minimal Minimal
Fludarabine (Fludara) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Fluorouracil (5-FU) Low Low Low
Gefitinib (Iressa) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Gemcitabine (Gemzar) Low Low Low
Hydroxyurea (Hydrea) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Idarubicin (Idamycin) Moderate High when given with Cyclophosphamide (Cytoxan)
Moderate when used alone
High: when combined with cyclophosphamide (in breast cancer patients) Moderate: when used alone
Ifosfamide (Ifex) High: 2000 mg/m2 or more per dose
Moderate: <2 g/m2 per dose
Moderate Moderate ASCO and MASCC did not subclassify based on dose
Imatinib (Gleevec) (oral) Low/Minimal Moderate Moderate NCCN did not further delineate between degrees of emetic potential
Interferon alfa-2a (Roferon-A) Moderate: 10 million international units/m2 or more
Low: between 5 and 10 million international units/m2
Minimal: 5 million international units/m2 or less
NCCN did not specify interferon alfa-2a vs. 2b
Interferon alfa-2b (Intron-A) Moderate: 10 million international units/m2 or more
Low: between 5 and 10 million international units/m2
Minimal: 5 million international units/m2 or less
NCCN did not specify interferon alfa-2a vs. 2b
Ipilimumab (Yervoy) Minimal Low
Irinotecan (Camptosar) Moderate Moderate Moderate
Ixabepilone (Ixempra) Low Low Low
Lapatinib (Tykerb) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Lenalidomide (Revlimid) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Lenvatinib (Lenvima) (oral) Moderate
Lomustine (CCNU) (oral) High/Moderate (single day) single day; NCCN did not further delineate between degrees of emetic potential
Lurbinectedin (Zepzelca) Moderate
Margetuximab (Margenza) Minimal
Mechlorethamine (Mustargen) High High High
Melphalan (Alkeran) Moderate ASCO and MASCC recommend combination of NK1+5-HT3+DEX when melphalan is used at high dose for BMT conditioning.
Melphalan (Alkeran) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Mercaptopurine (6-MP) (oral) Low/Minimal NCCN did not further delineate between degrees of emetic potential
Methotrexate (MTX) Moderate: 250 mg/m2 or more
Low: between 50 and 250 mg/m2
Minimal: 50 mg/m2 or less
Low Low ASCO and MASCC did not subclassify based on dose
Methotrexate (MTX) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Mitomycin (Mutamycin) Low Low Low
Mitotane (Lysodren) (oral) High/Moderate
Mitoxantrone (Novantrone) Low Low Low
Nelarabine (Arranon) Minimal
Nilotinib (Tasigna) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Niraparib (Zejula) (oral) Moderate to high NCCN did not further delineate between degrees of emetic potential (>30%)
Ofatumumab (Arzzera) Minimal Minimal
Omacetaxine (Synribo) Low
Olaparib (Lynparza) (oral) Moderate to high NCCN did not further delineate between degrees of emetic potential (>30%)
Oxaliplatin (Eloxatin) Moderate Moderate Moderate
Paclitaxel (Taxol) Low Low Low
Paclitaxel, nanoparticle albumin-bound (Abraxane) Low Low
Panitumumab (Vectibix) Minimal Low
Pazopanib (Votrient) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Peg-asparginase (Oncaspar) Minimal
Peginterferon alfa-2a (Pegasys) Minimal NCCN did not specify interferon alfa-2a vs. 2b
Peginterferon alfa-2b (Sylatron) Minimal NCCN did not specify interferon alfa-2a vs. 2b
Pembrolizumab (Keytruda) Minimal
Pemetrexed (Alimta) Low Low Low
Pentostatin (Nipent) Low
Pertuzumab (Perjeta) Minimal Low
Pixantrone (Pixuvri) Minimal
Pomalidomide (Pomalyst) (oral) Low/Minimal Minimal
Ponatinib (Iclusig) (oral) Low/Minimal Low
Pralatrexate (Folotyn) Low Minimal Minimal
Procarbazine (Matulane) (oral) High/Moderate High High NCCN did not further delineate between degrees of emetic potential
Regorafenib (Stivarga) (oral) Low/Minimal Low
Rituximab (Rituxan) Minimal Minimal Minimal
Romidepsin (Istodax) Low Moderate
Rucaparib (Rubraca) Moderate to high NCCN did not further delineate between degrees of emetic potential (>30%)
Ruxolitinib (Jakafi) (oral) Low/Minimal Minimal
Selinexor (Xpovio) (oral) Moderate/High Moderate/High NCCN and ASCO did not further delineate between degrees of emetic potential
Sorafenib (Nexavar) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Streptozocin (Zanosar) High High High
Sunitinib (Sutent) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Temozolmide (Temodar) Moderate Moderate MASCC remark: No direct evidence found for temozolomide IV. Classification is based on oral temozolomide, since all sources indicate a

similar safety profile

Temozolmide (Temodar) (oral) High/Moderate: >75 mg/m2/day
Low/Minimal: ≤75 mg/m2/day
Moderate Moderate NCCN did not further delineate between degrees of emetic potential
Temsirolimus (Torisel) Minimal Low
Thalidomide (Thalomid) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Thioguanine (Tabloid) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Thiotepa (Thioplex) Low Moderate
Topotecan (Hycamtin) Low Low Low
Topotecan (Hycamtin) (oral) Low/Minimal NCCN did not further delineate between degrees of emetic potential
Trabectedin (Yondelis) Moderate
Trametinib (Mekinist) (oral) Low/Minimal
Trastuzumab (Herceptin) Minimal Low Minimal
Trastuzumab deruxtecan (Enhertu) High Moderate
All-trans retinoic acid (ATRA) (oral) Low/Minimal NCCN did not further delineate between degrees of emetic potential
Umbralisib (Ukoniq) (oral) Low/Minimal
Valrubicin (Valstar) Minimal
Vandetanib (Caprelsa) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Vemurafenib (Zelboraf) (oral) Low/Minimal
Vinblastine (Velban) Minimal Minimal Minimal
Vincristine (Oncovin) Minimal Minimal Minimal
Vincristine liposomal (Marqibo) Minimal
Vinflunine (Javlor) Low
Vinorelbine (Navelbine) Minimal Minimal Minimal
Vinorelbine (Navelbine) (oral) Moderate
Vismodegib (Erivedge) (oral) High/Moderate Minimal
Vorinostat (Zolinza) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Ziv-aflibercept (Zaltrap) Low Low

Highly emetogenic IV chemotherapy (HEC)

Day 1 CINV prophylaxis Day 2-4 CINV prophylaxis
ASCO 2017 NK1 + 5-HT3 + DEX + OLN DEX + OLN

(if APR on day 1, then + APR days 2-3)

MASCC 2019 NK1 + 5-HT3 + DEX +/- OLN DEX +/- OLN

(if APR on day 1, then + APR days 2-3)

NCCN 2022 - NK1 + 5-HT3 + DEX + OLN DEX + OLN

(if po APR on day 1, then + APR days 2-3)

- NK1 + 5-HT3 + DEX DEX

(if po APR on day 1, then + APR days 2-3)

- OLN + Palonosetron + DEX OLN

Neurokinin-1 (NK1) antagonist-containing regimen (except netupitant)

Neurokinin 1 (NK1) antagonist

Note: All of the above NK1 antagonists are equally effective in IV and PO formulations at recommended doses [4]

Serotonin (5-HT3) antagonist

  • Dolasetron (Anzemet) 100 mg PO once on day 1
  • Granisetron (choose one of the options below):
    • 2 mg PO once on day 1
    • 0.01 mg/kg (maximum dose 1 mg) IV once on day 1
    • transdermal patch as 3.1 mg/24H patch (containing 34.3 mg granisetron total dose) placed ~24 to 48 hours before the first dose of chemotherapy. May use patch up to 7 days.
  • Ondansetron (Zofran) (choose one of the options below):
    • 8 to 16 mg IV[5] once on day 1
  • Palonosetron (Aloxi) 0.25 mg IV once on day 1
  • Tropisetron (Navoban) 5 mg IV or PO day 1

Note: When given at biologically equivalent doses, all of the above 5-HT3 antagonists are equally efficacious and appear to be interchangeable[6]

Note: Ramosetron is another available 5-HT3, but not approved by FDA

Dexamethasone (DEX)

Steroids contraindicated for use with interleukin-2 and interferon.

Dexamethasone use beyond day 1 might be revised based on the 2018 meta analysis results[7]

Netupitant-containing regimen

Olanzapine (OLN) containing regimen

Reference:

  1. Navari et al. 2016[8]

Moderately emetogenic IV chemotherapy (MEC)

Day 1 CINV prophylaxis Day 2-4 CINV prophylaxis
ASCO 2017 5-HT3 + DEX DEX maybe offered for: oxaliplatin, or anthracycline, or cyclophosphamide
MASCC 2016 5-HT3 + DEX DEX can be considered for: oxaliplatin, or anthracycline, or cyclophosphamide
NCCN 2022 - 5-HT3 + DEX DEX or 5-HT3
- NK1 + 5-HT3 + DEX

(for selected patients with additional risk factors or previous Rx failure)

Aprepitant PO daily days 2 and 3 if aprepitant POused on day 1

+/- DEX

- OLN + Palonosetron + DEX OLN

Serotonin (5-HT3) antagonist

  • Dolasetron (Anzemet) 100 mg PO once on day 1
  • Granisetron (choose one of the options below):
    • 2 mg PO once on day 1
    • 0.01 mg/kg (maximum dose 1 mg) IV once on day 1
    • transdermal patch as 3.1 mg/24H patch (containing 34.3 mg granisetron total dose) placed ~24 to 48 hours before the first dose of chemotherapy. May use patch up to 7 days.
  • Ondansetron (Zofran) (choose one of the options below):
    • 8 to 16 mg IV[5] once on day 1
  • Palonosetron (Aloxi) 0.25 mg IV once on day 1
  • Tropisetron (Navoban) 5 mg IV or PO day 1

Dexamethasone (DEX)

Steroids contraindicated for use with interleukin-2 and interferon.

Dexamethasone use beyond day 1 might be revised based on the 2018 meta analysis results[7]

Netupitant-containing regimen

Olanzapine (OLN) containing regimen

Note: a 4-drug regimen based on Navari et al. 2016[9]

Carboplatin based chemotherapy

Guideline and emetic risk Day 1 CINV prophylaxis Day 2-4 CINV prophylaxis
ASCO 2017 (MEC)

AUC 4 or more

NK1 + 5-HT3 + DEX NONE

(if APR on day 1, then +APR days 2-3)

MASCC 2019 (MEC)

(doesn’t specify AUC)

NK1 + 5-HT3 + DEX NONE

(if APR on day 1, then +APR days 2-3)

NCCN 2019

AUC 4 or more (HEC)

AUC less than 4 (MEC)

NK1 + 5-HT3 + DEX DEX
5-HT3 + DEX

Recommendation to add NK1 is largely based on 2 phase III studies[10][11]. One of them was conducted in female patients with GYN malignancy only. [10] 5-HT3 used in those trials was either granisetron or ondansetron.

Bone marrow transplant (BMT) conditioning regimens

Note: Day 0 is the day of BMT, days with "-" in front are days prior to transplant, days with "+" afterwards are days after transplant

Allogeneic BMT conditioning regimens

Conditioning regimen CINV prophylaxis
FMT (fludarabine, melphalan, thiotepa) - NK1 on day -7

- 5-HT3 on days -7 to -1

Flu/Mel (fludarabine, melphalan) - NK1 on day -2

- 5-HT3 on days -6 to -1

- DEX on days -6 to -1

Flu/Cy/TBI (fludarabine, cyclophosphamide, total body irradiation)
Cy/TBI (cyclophosphamide, total body irradiation) - NK1 on day -6

- 5-HT3 on days -6 to -1

- DEX on days -6 to -4

Bu/Flu (bufulfan, fludarabine)
Bu/Cy (busulfan, cyclophosphamide)

Autologous BMT conditioning regimens

Conditioning regimen CINV prophylaxis
High dose melphalan[12] - NK1 on days -3 to 0

- 5-HT3 on days -3 to 0

- DEX on days -3 to -1

BEAM (busulfan, etoposide, cytarabine, melphalan)
TBC (thiotepa, busulfan, cyclophosphamide)


Highly to moderately emetogenic PO chemotherapy

These are NCCN recommendations only. ASCO did not provide separate antiemetic recommendations for PO vs. IV chemotherapy.
Start before chemotherapy and continue once per day:

Serotonin (5-HT3) antagonist

Optional

Low emetic risk IV chemotherapy

Day 1 Day 2-4
ASCO 2017 Single dose 5-HT3 or DEX 8mg No routine prophylaxis
MASCC 2016 5-HT3 or DEX or Dopamine RA No routine prophylaxis
NCCN 2022 DEX or Metoclopramide or Prochlorperazine or

5-HT3 other than Palonosetron

No routine prophylaxis

Repeat once per day for chemotherapy regimens that last more than one day.

Minimal emetic risk chemotherapy

  • No routine prophylaxis recommended by all 3 guideline groups. Assess patient prior to cycle 2 and add single agent prophylactic antiemetic if patient had emesis with cycle 1.

Low to minimal emetic risk PO chemotherapy

  • use antiemetics prn first

If nausea/vomiting

Choose one of the medications below to start before chemotherapy and continue once per day:

Optional

If continued nausea/vomiting

Use serotonin (5-HT3) antagonist:

Breakthrough CINV treatment

General Principles

-Use antiemetic from another class than the prophylactic regimen

-Agents which are successful in treating a patient’s breakthrough CINV should be given routinely for a period of time rather than on an as needed basis.

-5-HT3 and NK1 RA are generally not effective or approved for treatment of breakthrough nausea/vomiting (assuming they were used as part of prophylaxis)

Olanzapine

  • Olanzapine (Zyprexa) 10 mg PO daily on days 1-3 if CINV develop in the first 24 hours after HEC [13]. Use 5 mg if 10 mg is not well tolerated.[14]

Metoclopromide

Benzodiazepine

Cannabinoid

Other agents

Serotonin 5-HT3 antagonists

Are generally ineffective for breakthrough CINV (assuming they were used as part of prophylactic regimen).

Anticipatory nausea/vomiting

  • Prevent anticipation by optimizing antiemetic therapy for every cycle of chemotherapy
  • Behavioral therapy
    • Relaxation/systemic desensitization
    • Hypnosis/guided imagery
    • Music therapy
  • Acupuncture/acupressure
  • Alprazolam (Xanax) 0.5 to 2 mg PO three times per day starting the night before treatment
  • Lorazepam (Ativan) 0.5 to 1 mg PO beginning the night before treatment and then repeat the next 1-2 hours before anticancer therapy begins

Reference

  1. NCCN antiemesis guidelines
  2. ASCO antiemesis guidelineshttps://ascopubs.org/doi/abs/10.1200/JCO.20.01296
  3. MASCC antiemetic guidlines https://www.mascc.org/antiemetic-guidelines
  4. Grunberg S, Chua D, Maru A, Dinis J, DeVandry S, Boice JA, Hardwick JS, Beckford E, Taylor A, Carides A, Roila F, Herrstedt J. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE. J Clin Oncol. 2011 Apr 10;29(11):1495-501. Epub 2011 Mar 7. link to original article PubMed
  5. 5.0 5.1 As of 6/28/2012, the once daily dose of ondansetron (Zofran) 32 mg is no longer recommended due to dose-dependent QTc prolongation. The Ondansetron (Zofran) package insert recommends only a maximum of 16 mg per dose, which can be given as often as every 4 hours x up to 3 doses, as detailed in the 6/29/2012 FDA Drug Safety Communication.
  6. Karin Jordan et al. "Comparative activity of antiemetic drugs" https://www-sciencedirect-com.elibrary.einstein.yu.edu/science/article/pii/S1040842806001661#tbl2
  7. 7.0 7.1 Ronald CHow et Al. "Efficacy and safety of 1-day versus 3-day dexamethasone for the prophylaxis of chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials" http://jhmhp.amegroups.com/article/view/4296
  8. Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, Dietrich L, Biggs D, Lafky JM, Loprinzi CL. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Jul 14;375(2):134-42. link to original article PubMed
  9. Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, Dietrich L, Biggs D, Lafky JM, Loprinzi CL. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Jul 14;375(2):134-42. link to original article PubMed
  10. 10.0 10.1 Yahata H, Kobayashi H, Sonoda K, et al: Effi- cacy of aprepitant for the prevention of chemotherapy- induced nausea and vomiting with a moderately emetogenic chemotherapy regimen: A multicenter, placebo-controlled, double-blind, randomized study in patients with gynecologic cancer receiving pac- litaxel and carboplatin. Int J Clin Oncol 21:491-497, 2016 https://pubmed.ncbi.nlm.nih.gov/26662632
  11. Hesketh PJ, Schnadig ID, Schwartzberg LS, et al: Efficacy of the neurokinin-1 receptor antagonist rolapitant in preventing nausea and vomiting in pa- tients receiving carboplatin-based chemotherapy. Cancer 122:2418-2425, 2016https://pubmed.ncbi.nlm.nih.gov/27176138
  12. . 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. PubMed ID 25225424.
  13. 13.0 13.1 R. M. Navari, C. K. Nagy, and S. E. Gray, “The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy,” Supportive Care in Cancer, vol. 21, no. 6, pp. 1655–1663, 2013
  14. S. Chanthawong, S. Subongkot, and A. Sookprasert, “Effectiveness of olanzapine for the treatment of breakthrough chemotherapy induced nausea and vomiting,” Journal of the Medical Association of Thailand, vol. 97, pp. 349–355, 2014