Chapter 39: Prophylaxis and Treatment of Chemotherapy-Induced Nausea and Vomiting

Thomas E. Hughes

INTRODUCTION

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Chemotherapy-Induced Nausea and Vomiting (CINV)

Neurotransmitters and their receptor targets implicated in CINV

Serotonin and the serotonin subtype 3 (5-HT₃) receptor
Dopamine and the dopamine subtype 2 (D₂) receptor
Substance P and the neurokinin subtype 1 (NK₁) receptor
Histamine, acetylcholine, opioids, and their respective receptors

Two Phases of CINV

Acute phase

Occurs during the first 24 hours after exposure to emetogenic chemotherapy and is mediated by release of serotonin from enterochromaffin cells within GI tract
Actual time of onset varies depending on the chemotherapeutic agent

Delayed phase

Substance P and the NK₁ receptor may be more important than serotonin in delayed CINV
Delayed CINV was initially described with cisplatin
Delayed CINV has also been described with other chemotherapeutic agents, including carboplatin, cyclophosphamide, and the anthracyclines
Although the onset of delayed emesis was initially defined as that which occurs 24 hours postchemotherapy, more recent evidence suggests that referable symptoms may occur as early as 16 hours after cisplatin
The incidence of delayed vomiting after cisplatin is greatest during the 24-hour period from 48 to 72 hours after treatment, and, thereafter, declines progressively

Anticipatory Nausea and Vomiting

Development is associated with poor emetic control during prior administration of chemotherapy
Prevention is the best approach
Pharmacologic interventions are usually not successful, but behavioral methods with systemic desensitization is effective and has been used with some success

Antiemetic Principles^{1,2,3,4,5,6,7}

5-HT₃ receptor antagonists demonstrate comparable efficacy at equivalent doses. In general, they can be used interchangeably based on convenience, availability, and cost. Evidence from clinical trials suggests palonosetron may be more effective than other 5-HT₃-receptor antagonists in preventing delayed CINV. Clinical practice guidelines from the Multinational Association of Supportive Care in Cancer (2010), and the American Society of Clinical Oncology (2011 update) recommend palonosetron as the preferred 5-HT₃ receptor antagonist in prophylaxis for chemotherapy of moderate emetic potential when aprepitant is not included in the regimen.^2,4,6 The National Comprehensive Cancer Network antiemesis guideline (version 1.2012) recommends palonosetron as the preferred 5-HT₃ receptor antagonist in prophylaxis for both high and moderate emetic risk categories³
The lowest established proven dose of each 5-HT₃ receptor antagonist should be used
Single-dose prophylactic regimens of 5-HT₃ receptor antagonists and corticosteroids for acute phase CINV prophylaxis are effective and preferred
At biologically equivalent doses, oral antiemetic regimens are equivalent to intravenous antiemetic regimens
All patients receiving chemotherapy should have antiemetics available on a PRN basis for breakthrough nausea and vomiting. Rescue agents should be selected to complement, not duplicate the prophylactic regimen (ie, select drugs from a different pharmacologic class)
For CINV prophylaxis where there is a high emetic potential (emetic incidence of >90%), an antiemetic regimen that includes a 5-HT₃ receptor antagonist, a corticosteroid, and aprepitant (NK₁ receptor antagonist) is recommended. This antiemetic regimen is also recommended for combination chemotherapy regimens that include an anthracycline (eg, doxorubicin, epirubicin) and cyclophosphamide (see Table 39-4)
For CINV prophylaxis where there is a moderate emetic potential (emetic incidence of 30–90%), an antiemetic regimen that includes a 5-HT₃ receptor antagonist and a corticosteroid is recommended (see Table 39-4)
A corticosteroid alone is the recommended prophylactic regimen for low or intermediate emetic potential chemotherapy (emetic incidence of 10–30%)

Table 39–1.Antiemetic Pharmacologic Classes and Class Side Effects

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Table 39–1. Antiemetic Pharmacologic Classes and Class Side Effects

Pharmacologic Class

Agents/Generic Name (Trade Name) (U.S. FDA Approved)

Side-Effects Profile^{8,9,10,11,12,13}

5-HT₃ receptor antagonists

Dolasetron (Anzemet)

Granisetron (Kytril, Sancuso)

Ondansetron (Zofran)

Palonosetron (Aloxi)

Headache [C]

Constipation [I]

Light-headedness or dizziness [I]

Transient elevations in liver enzymes [I]

ECG interval changes: Prolongation of PR, QTc, and JT, and widening of QRS (especially dolasetron) [R]

Corticosteroids

Dexamethasone (Decadron, generic products)

Methylprednisolone (Solu-Medrol, generic products)

Hyperglycemia

Mood changes

Increased appetite

Diarrhea

Perineal irritation with rapid IV administration of dexamethasone

Fluid retention

NK₁ receptor antagonists

Aprepitant (Emend)

Fosaprepitant (Emend)

In randomized trials, treatment side effects were similar with or without aprepitant

Dopaminergic antagonists: Phenothiazines

Chlorpromazine (Thorazine, generic products)

Perphenazine (Trilafon, generic products)

Prochlorperazine (Compazine, generic products)

Promethazine (Phenergan, generic products)

Thiethylperazine (Torecan, generic products)

Extrapyramidal side effects^✫

Sedation

Anticholinergic effects

Hypotension with rapid IV administration, hypersensitivity

Hepatotoxicity

Cholestatic jaundice

Leukopenia and agranulocytosis

Hormonal dysfunction

Neuroleptic malignant syndrome^†

Cardiovascular effects^‡

Dopaminergic antagonists: Butyrophenones

Droperidol (Inapsine)

Haloperidol (Haldol, generic products)

Extrapyramidal side effects^✫

Sedation

Agitation

Dizziness

Chills

Hallucinations

Hypotension or hypertension

Prolongation of ECG intervals (QT prolongation)

Arrhythmias (eg, torsades de pointes)

Substituted benzamides

Metoclopramide (Reglan)

Trimethobenzamide (Tigan)

Sedation

Diarrhea

Extrapyramidal side effects^✫

Neuroleptic malignant syndrome^†

Hypotension

Arrhythmias

Benzodiazepines

Lorazepam (Ativan)

Alprazolam (Xanax)

Sedation

Lethargy

Weakness

Impaired coordination

Cannabinoids

Dronabinol (Marinol)

Nabilone (Cesamet)

Mood changes

Memory loss

Euphoria

Dysphoria

Hallucinations

Sedation

Paranoid ideation

Ataxia

Motor incoordination

Blurred vision

Hunger

Cardiovascular effects^§

Syncope

Atypical Antipsychotics

Olanzapine (Zyprexa)

Mirtazapine (Remeron)

Sedation

Extrapyramidal side effects^✫

Neuroleptic malignant syndrome^†

Weight gain, hyperglycemia, and other features of metabolic syndrome may be seen with high doses and prolonged use

Antihistamines

Diphenhydramine (Benadryl, generic products)

Hydroxyzine (Atarax, generic products)

Meclizine (Antivert, generic products)

Sedation

Dry mouth

Constipation

Blurred vision

Anticholinergics

Scopolamine (Transderm Scōp)

Dry mouth

Somnolence

Sedation

Constipation

C, common; I, infrequent; R, rare. For other agents, order of frequency is less clear

^✫Extrapyramidal side effects: Akathisia, dyskinesias, parkinsonism, acute dystonias (oculogyric crisis, torticollis)

^†Neuroleptic malignant syndrome: Hyperthermia, severe extrapyramidal dysfunction (eg, severe hypertonicity of skeletal muscles, altered mental status and/or level of consciousness, and autonomic instability)

^‡Phenothiazine cardiovascular effects include hypotension, syncope, hypertension, bradycardia, and various ECG changes (nonspecific, reversible Q- and T-wave abnormalities). Cases of sudden death have also been reported, presumably secondary to ventricular arrhythmias

^§The cardiovascular adverse effects of dronabinol are inconsistent but the following have been reported during therapy: hypotension, hypertension, syncope, tachycardia, palpitations, vasodilation, and facial flushing

Table 39–2.Pharmacokinetic Parameters of 5-HT₃ Receptor Antagonists^{8,9,10,11,12,13,14}

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Table 39–2. Pharmacokinetic Parameters of 5-HT₃ Receptor Antagonists^{8,9,10,11,12,13,14}

Parameter

Ondansetron (0.15 mg/kg IV)

Granisetron (40 mcg/kg IV)

Dolasetron^✫ (1.8 mcg/kg IV)

Palonosetron (10 mcg/kg IV)

Half-life (hours)

4.0^†

8.95^†

7.5^†

40^‡

Protein binding

70–76%

65%

69–77%

62%

Oral bioavailability

56%

60%

75%

Metabolism

CYP enzymes

Hepatic

CYP3A4 (major)

CYP2D6, CYP1A2

Hepatic

CYP3A4

Hepatic

CYP2D6 (major)

CYP3A4 (minor)

Hepatic

CYP2D6 (major)

CYP3A4, 1A2

Urinary excretion (parent compound)

12%

67%

40%

Decreased clearance in elderly

Dosage adjustment in elderly

Yes

Decreased clearance in hepatic dysfunction

Dosage adjustment in hepatic dysfunction

Yes

Yes (in severe dysfunction)

Yes

No (IV), Yes (PO)

Decreased clearance in renal dysfunction

Dosage adjustment in renal dysfunction

Yes

^✫Dolasetron is rapidly converted to the active metabolite hydrodolasetron. All reported parameters refer to hydrodolasetron

^†Data from cancer patients

^‡Data from studies in healthy volunteers

Table 39–3.Classification of Emetic Risk^1,2,3,4

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Table 39–3. Classification of Emetic Risk^1,2,3,4

Emetic Potential

Chemotherapy Drug

High

Frequency of emesis >90%

Carmustine (>250 mg/m²)^1,3

Cisplatin (≥50 mg/m²)^1,3,4

Cyclophosphamide (>1500 mg/m²)^1,2,3,4

Dacarbazine^1,2,3,4

Lomustine (>60 mg/m²)¹

Mechlorethamine^1,2,3,4

Streptozocin^1,2,3,4

Moderate

Frequency of emesis 30–90%

Aldesleukin (IL-2) (>12–15 million IU/m²)³

Altretamine³

Arsenic Trioxide³

Azacitidine^3,4

Bendamustine^3,4

Busulfan (IV, oral >4 mg/kg per day)^3,✫

Carboplatin^1,2,3,4

Carmustine (≤250 mg/m²)^1,3

Cisplatin (<50 mg/m²)^1,3

Clofarabine^3,4

Cyclophosphamide (<1500 mg/m²)^1,2,3,4

Cytarabine (>1000 mg/m²)^1,2,4

Dactinomycin³

Daunorubicin^2,3,4

Doxorubicin^1,2,3,4

Epirubicin^2,3,4

Idarubicin^1,2,3,4

Interferon alfa (≥10 million IU/m²)³

Ifosfamide^1,2,3,4

Irinotecan^1,2,3,4

Melphalan (IV)^1,3

Methotrexate (>250 mg/m²)^1,3

Oxaliplatin^2,3,4

Pentostatin^✫

Procarbazine¹

Romidepsin^✫

Temozolomide^3,4

Low

Frequency of emesis 10–30%

Aldesleukin (IL-2) (<12 million IU/m²)³

Bortezomib^2,4

Cabazitaxel³

Capecitabine⁴

Cetuximab^2,4

Cytarabine (<1000 mg/m²)^1,2,4

Daunorubicin, Liposomal^✫

Decitabine^✫

Denileukin diftitox^✫

Docetaxel^1,2,3,4

Doxorubicin, Liposomal^3,4

Eribulin³

Etoposide^1,2,3,4

Everolimus⁴

Fluorouracil^2,3,4

Gemcitabine^1,2,3,4

Imatinib^✫

Interferon alfa (>5 to <10 million IU/m²)³

Ixabepilone^3,4

Lapatinib⁴

Lenalidomide⁴

Methotrexate (>50 mg/m² to <250 mg/m²)^1,3

Mitomycin^1,2,3,4

Mitoxantrone^2,3,4

Nelarabine^✫

Paclitaxel^1,2,3,4

Paclitaxel, albumin-bound suspension³

Panitumumab⁴

Pazopanib^✫

Pemetrexed^2,3,4

Pralatrexate³

Sunitinib⁴

Temsirolimus⁴

Teniposide¹

Thalidomide⁴

Thiotepa¹

Topotecan^1,2,3,4

Minimal

Frequency of emesis <10%

Alemtuzumab³

Asparaginase³

Bevacizumab^3,4

Bleomycin^1,2,3,4

Busulfan (oral, <4 mg/kg per day)¹

Chlorambucil^1,4

Cladribine^1,2,3,4

Dasatinib^✫

Erlotinib⁴

Fludarabine^1,2,3,4

Gefitinib⁴

Hydroxyurea^1,4

Interferon alfa (≤5 million IU/m²)³

Ipilimumab³

Melphalan (oral)^1,4

Mercaptopurine¹

Methotrexate (<50 mg/m²)^1,3,4

Nilotinib^✫

Ofatumumab³

Pegaspargase³

Rituximab^2,3,4

Sorafenib⁴

Thioguanine (oral)^1,4

Trastuzumab³

Vinblastine^1,2,3,4

Vincristine^1,2,3,4

Vinorelbine^1,2,3,4

Classifications are adapted from references 1–4. Each agent is referenced to a specific guideline. When discrepancies existed among guidelines, the author classified the agent on personal opinion and referenced the guideline that supported the classification chosen. If the agent was not classified by a clinical guideline or the clinical guideline classification was in doubt, the classification was based on the incidence of emesis documented in product labeling

^✫Classified based on the incidence of emesis documented in product labeling

Table 39–4.Antiemetic Regimens for Prophylaxis of CINV (Adults)^1,2,3,4

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Table 39–4. Antiemetic Regimens for Prophylaxis of CINV (Adults)^1,2,3,4

Emetic Potential

Acute Nausea and Vomiting Antiemetic Regimen (First 24 Hours, Day 1)

Delayed Nausea and Vomiting Antiemetic Regimen (>24 Hours, Days 2–5)

Notes and Comments

High

Frequency of emesis >90%

5-HT₃ antagonist + corticosteroid + aprepitant (all given as single doses 30–60 minutes prior to chemotherapy)

Aprepitant + corticosteroid

See Table 39-3 for emetic risk classification of chemotherapy agents and regimens

Agents associated with delayed CINV include cisplatin, carboplatin, cyclophosphamide, anthracyclines (eg, doxorubicin, epirubicin) and drug combinations that include these agents

See Table 39-5 for dosing recommendations for antiemetic agents

Corticosteroids should not be used with regimens containing aldesleukin (IL-2)

Moderate

Frequency of emesis 30–60%

5- HT₃ antagonist + corticosteroid ± aprepitant (all given as single doses 30–60 minutes prior to chemotherapy)

Aprepitant (if aprepitant is used for acute prophylaxis)

Corticosteroid

5-HT₃ antagonist

See above

Aprepitant should be utilized in patients treated with the combination of cyclophosphamide and an anthracycline (eg, doxorubicin or epirubicin). Aprepitant may be considered for other moderately emetogenic regimens, particularly in refractory patients

Low

Frequency of emesis 10–30%

Corticosteroid (a single dose 30 minutes prior to chemotherapy

Dopaminergic antagonist (a single dose 30 minutes prior to chemotherapy)

Note: Antiemetic prophylaxis may often be unnecessary

Not necessary

Dopaminergic antagonists include prochlorperazine, chlorpromazine, haloperidol, thiethylperazine, metoclopramide, perphenazine, and promethazine

Minimal

Frequency of emesis <10%

Antiemetic prophylaxis is usually not necessary

Not necessary

See above

Table 39–5.Dosing Recommendations for CINV Prophylaxis (Adults) for Moderate to Highly Emetic Chemotherapy^1,2,3,4

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Table 39–5. Dosing Recommendations for CINV Prophylaxis (Adults) for Moderate to Highly Emetic Chemotherapy^1,2,3,4

Agent

Acute CINV Prophylaxis (Day 1)^✫

Delayed CINV Prophylaxis (Days 2–5)

Dosage Forms

Oral (PO)

Intravenous (IV)

Other

5-HT₃ Receptor Antagonists

Dolasetron mesylate (Anzemet)

100 mg PO

Not recommended

100 mg PO daily for 2–4 days

Injection

Tablets: 50 mg, 100 mg

Granisetron HCl (Kytril)

2 mg PO

1 mg or 0.01 mg/kg IV

1 mg PO twice daily for 2–4 days

Injection

Tablets: 1 mg

Granisetron HCl (Sancuso)

Apply 1 patch to the upper outer arm 24–48 hours before chemotherapy

Patches are removed a minimum of 24 hours after emetogenic treatment is completed, and may be worn for up to 7 days

Transdermal system: 52-cm² patch delivers 3.1 mg/24 hours

Ondansetron HCl (Zofran)

16–24 mg PO

8 mg or 0.15 mg/kg IV

8 mg PO twice daily for 2–4 days

Injection

Tablets: 4 mg, 8 mg, 24 mg

Oral solution: 4 mg/5 mL

Orally disintegrating tablets: 4 mg, 8 mg

Ondansetron (Zuplenz)

8 mg PO, 30 minutes before emetogenic treatment, then 8 mg PO 8 hours after emetogenic treatment

8 mg PO every 12 hours for 1–2 days

Oral soluble film: 4 mg, 8 mg

Palonosetron HCl (Aloxi)

0.5 mg PO, 60 minutes before emetogenic treatment

0.25 mg IV

Injection

Oral capsules^‡: 0.5 mg

Notes:

Because of its long half-life, palonosetron is usually given as a single dose prior to moderately and highly emetogenic chemotherapy with demonstrable efficacy against developing delayed CINV symptoms on subsequent days
When utilized as prophylaxis in a multiple-day chemotherapy regimen, alternative palonosetron administration strategies have been employed (eg, days 1, 3, and 5, during a chemotherapy regimen in which cisplatin 20 mg/m² is given daily for 5 consecutive days)

Corticosteroids

Dexamethasone phosphate (Decadron)

8–20 mg PO

8–20 mg IV

4 mg twice daily or 8 mg PO daily or 8 mg twice daily for 2–4 days

Injection

Tablets: numerous tablet strengths

Methylprednisolone sodium succinate (Solu-Medrol)

40–125 mg IV

Injection

Notes:

For highly emetogenic chemotherapy, dexamethasone doses of 20 mg have been shown to be more efficacious than lower doses. In moderately emetogenic chemotherapy, doses greater than 8 mg have not been shown superior to an 8-mg dose
When combined with aprepitant, IV doses of dexamethasone should be reduced by 25%, and PO doses of dexamethasone should be reduced by 50%. A 12-mg dose of dexamethasone for acute prophylaxis in combination with aprepitant is the only dexamethasone dose evaluated in large randomized trials

NK₁ Receptor Antagonists

Aprepitant (Emend)

125 mg PO

80 mg PO daily for 2 days

Capsules: 80 mg, 125 mg

Fosaprepitant (Emend)

115 mg IV

150 mg IV

Not evaluated

Injection

Notes:

Aprepitant has been evaluated only in single-day chemotherapy regimens, and, therefore, is recommended to be given for 3 days, with an initial dose of aprepitant 125 mg on the day of chemotherapy plus 80 mg/day on days 2 and 3 after emetogenic treatment. If utilized in a multiple-day chemotherapy regimen, longer durations may be indicated (80 mg/day); however, the safety of durations exceeding 5 days has not been studied
Fosaprepitant has been evaluated in 2 dosing formats. It may be used in a 3-day regimen with fosaprepitant 115 mg IV on day 1, followed by 80 mg/day orally on days 2 and 3 after chemotherapy. It has also been studied in a single-dose regimen with fosaprepitant 150 mg on day 1 prior to chemotherapy with no additional aprepitant doses administered subsequently during the same course of emetogenic treatment. The single-dose fosaprepitant regimen was shown to be non-inferior to the alternative 3-dose aprepitant regimen in a randomized study of patients receiving a highly emetogenic, cisplatin-based chemotherapy regimen¹⁷

NA, Not applicable

^✫For chemotherapy/biologic regimens where emetogenic agents are given either multiple times within the same day or by continuous IV infusions, alternative multiple-dose antiemetic regimens may be indicated

^†Delayed CINV has been associated with cisplatin, carboplatin, cyclophosphamide, and anthracyclines (eg, doxorubicin, epirubicin)

^‡As of October 24, 2013, palonosetron capsules for oral administration are not commercially available in the United States

Table 39–6.Antiemetics for Treatment of Chemotherapy-Induced Nausea and Vomiting (Adults)

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Table 39–6. Antiemetics for Treatment of Chemotherapy-Induced Nausea and Vomiting (Adults)

Pharmacologic Classes/Agents

Dosage Form

Adult Dosages, Routes, and Schedules

Dopaminergic Antagonists: Phenothiazines

Chlorpromazine (Thorazine, others)

Oral solution

25–50 mg PO every 4–6 hours

Tablets

25–50 mg PO every 4–6 hours

Injection

25–50 mg IVPB/IM every 4–6 hours^✫

Perphenazine (Trilafon)

Tablets

2–4 mg PO every 8 hours

Prochlorperazine (Compazine, others)

Tablets

5–20 mg PO every 4–6 hours

Sustained release capsules

15 mg PO every 8–12 hours, or

30 mg PO every 12 hours

Suppositories

25 mg PR every 4–6 hours

Injection

5–20 mg IVPB/IM every 4–6 hours^✫

Promethazine (Phenergan)

Tablets

12.5–25 mg PO every 4–6 hours

Suppositories

12.5–25 mg PR every 4–6 hours

Injection

12.5–25 mg IV every 4–6 hours^†

Thiethylperazine (Torecan)

Tablets

10–20 mg PO every 4–6 hours

Dopaminergic Antagonists: Butyrophenones

Haloperidol (Haldol, others)

Tablets

1–4 mg PO every 6 hours

Injection

1–4 mg IVPB/IM every 6 hours^✫

Substituted Benzamide

Metoclopramide (Reglan, others)

Tablets

20–40 mg (or 0.5 mg/kg) PO every 6 hours

Injection

20–40 mg (or 0.5 mg/kg) IV every 6 hours^‡

Corticosteroids

Dexamethasone

Tablets/oral solution

4–10 mg PO every 6–12 hours

Injection

4–10 mg IV every 6–12 hours

Methylprednisolone

Injection

20–125 mg IV/IM every 6 hours

Benzodiazepines^§

Alprazolam (Xanax)

Tablets

0.125–0.5 mg PO every 8 hours

Lorazepam (Ativan)

Tablets

0.5–1 mg PO every 6–12 hours

Injection

0.5–1 mg IV every 6–12 hours

Cannabinoids

Dronabinol (Marinol)

Capsules

2.5–10 mg PO every 6 hours

Nabilone (Cesamet)

Capsules

1–2 mg PO every 8–12 hours

IM, Intramuscular; IV, intravenously; IVPB, IV piggyback (IV infusion of short duration); PO, orally; PR, per rectum (suppository)

^✫Rapid IV administration may induce hypotension. Administer slowly by IV infusion (eg, over 30 minutes)

^†Promethazine injection is a potential vesicant. Use caution with intravenous administration, particularly during administration into a peripheral vein. Drug dilution and -administration by IV infusion are techniques that may reduce vascular irritation

^‡Greater metoclopramide doses have been utilized for the prophylaxis of CINV for highly emetic chemotherapy

^§Benzodiazepines lack intrinsic antiemetic effects and should not be used as single agents against emetogenic chemotherapy

REFERENCES

Listen

ASHP therapeutic guidelines on the pharmacologic management of nausea and vomiting in adult and pediatric patients receiving chemotherapy or radiation therapy or undergoing surgery. Am J Health Syst Pharm 1999;56:729–764 [PubMed: 10326616]

Basch E, Prestrud AA, Hesketh PJ et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2011;29:4189–4198 [PubMed: 21947834]

Antiemesis. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), version 1.2012, National Comprehensive Cancer Care Network, 20 July 2011. Available from: http://www.nccn.org

MASCC/ESMO Antiemetic Guidelines 2010, Multinational Association of Supportive Care in Cancer, Nov. 3, 2010, http://www.mascc.org/mc/page.do?sitePageId=88041

Kris MG, Tonato M, Bria E et al. Consensus recommendations for the prevention of vomiting and nausea following high-emetic-risk chemotherapy. Support Care Cancer 2010;19(Suppl 1):S25–S32 [PubMed: 20803039]

Herrstedt J, Rapoport B, Warr D et al. Acute emesis: moderately emetogenic chemotherapy. Support Care Cancer 2010;19(Suppl 1):S15–S23 [PubMed: 20680356]

Einhorn LH, Grunberg SM, Rapoport B et al. Antiemetic therapy for multiple-day chemotherapy and additional topics consisting of rescue antiemetics and high-dose chemotherapy with stem cell transplant: review and consensus statement. Support Care Cancer 2010;19(Suppl 1):S1–S4 [PubMed: 20505956]

Zofran (ondansetron hydrochloride) injection for intravenous use [package insert]. Research Triangle Park, NC: GlaxoSmithKline, September 2011

Zofran (ondansetron hydrochloride) Tablets, Zofran ODT (ondansetron) Orally Disintegrating Tablets, Zofran (ondansetron hydrochloride) Oral Solution [package insert]. Research Triangle Park, NC: GlaxoSmithKline, September 2011 [PubMed: NBK311303] [PubMed: 4111872]

10.

Kytril (granisetron hydrochloride) Tablets, Oral Solution [package insert]. Nutley, NJ: Roche Laboratories, Inc., March 2010

11.

Kytril (granisetron hydrochloride) injection for intravenous use [package insert]. Nutley, NJ: Roche Laboratories, Inc., April 2011

12.

Anzemet (dolasetron mesylate) tablets [package insert]. Bridgewater NJ: Sanofi-Aventis, U.S., LLC, September 2011

13.

Aloxi (palonosetron HCl) injection for Intravenous Use [package insert]. Woodcliff Lake, NJ: Eisai, Inc., September 2008

14.

Aloxi (palonosetron HCl) Capsules [package insert]. Woodcliff Lake, NJ: Eisai, Inc., August 2008

15.

Emend (aprepitant) Capsules [package insert]. Whitehouse Station, NJ: Merck & Co., Inc., March 2011

16.

Davidson TG. Causes and prevention of chemotherapy-induced emesis. Philadelphia: Medical Education Systems, Inc., 1996;34–35

17.

Emend (fosaprepitant dimeglumine) for Injection, for intravenous use [package insert]. Whitehouse Station, NJ: Merck & Co., Inc., March 2011

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Chapter 39: Prophylaxis and Treatment of Chemotherapy-Induced Nausea and Vomiting

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