Anti-emetics for chemotherapy A practice guideline

J Clin Oncol 2006;24:2932-2947 R5

Anti-emetics in chemotherapy
Highest therapeutic index medication
5-HT3 serotonin receptor antagonists Corticosteroids NK1 receptor antagonists

Lower therapeutic index medication

Metoclopramide, Butyrophenones, Phenothiazines, Cannabinoids.

Adjunctive drugs
Benzodiazepines antihistamines

 (5HT3 inhibitor)
/
ondansetron 8~32mggranisetron 1~3mg tropisetron 5mg ondansetron 8~32mggranisetron 1~3mg tropisetron 5mg dexamethasone metoclopramide dexamethasone metoclopramide


cisplatin(>50mg/m2/day) carmustine(250mg /m2 /day),cyclophosphamide (>1500mg/m2/day)methotrexate (1.2gm/m2 /day) cisplatin(30mg/m2/day 50mg/m2/day)carmustine(<250mg/m2/day), cyclophosphamide(1500 mg/m2/day)doxorubicin (45mg /m2 /day)epirubicin (70mg/ m2 /day)CPT11idarubicin(10mg/ m2 /day)daunorubicin (60mg/ m2 /day )dactinomycin(actinomycin-D) arsenic trioxidemelphalan (50 mg/m2/day) cytarabinecarboplatinoxaliplatinifosfamide mitoxantronedacarbazine

 (NK-1 inhibitor)
dexamethasone5HT3 5HT3 carmustine(250mg /m2 /day),cyclophosphamide (>1500mg/m2/day), methotrexate 1.2gm/m2 /day cisplatin>50mg/m2

Pathophysiology of Nause and Vomiting

The emetic center receives input from: Chemotehrapy trigger zone(CTZ)
Mediated by dopamine, serotonin, substance-P

Vagal afferent center

Mediated by serotonin

Cerebral cortex
May be involved with anticipator N/V Mediated by dopamine and serotonin

Chemotherapy induced Emesis

Acute emesis() Delayed emesis() Anticipatory emesis()

Acute The intensity peaks after 26hrs, occurs more often and tend to be more severe than delayed emetic episodes

Delayed

Anticipatory

Peak incidence 10-60% incidence occurring at 48rate 72h. Commonly found with cisplatin, carboplatin, cyclophosphamid e,doxorubicin

Other causes of emesis

Partial or complete bowel obstruction Vestibular dysfunction Brain metastases Electrolyte imbalance Uremia Concomitant drug treatments opiates Gastroparesis Psychophysiologic

Principles of emesis control

Prevention of nausea/vomiting is the goal Emesis risk last for at least 4 days Use the lowest tested fully effective dose Intravenous and oral formulations are equally effective and safe Consider toxicity of specific antiemetic Choice of antiemetic based on emetic risk of the chemotherapy as well as patient factors

Factors increase susceptibility to CINV

Hx of motion sickness Hx of moderate/severe sickness during pregnancy Recent exposure to anesthetics Recent abdominal, ophthalmic, or cranial surgery Concomitant use of nauseogenic drugs Raised BUN Anxiety Female gender Asian ethnicity

Factors decrease susceptibility to CINV

Alcohol consumption Smoking Old age Cannabinoid use

Acute Emesis
Vomiting occurring 0-24 hrs after therapy Emetic risk categories
High Moderate Low Minimal

Classification based on experience rather than on specific data

Anti-emetic agent
Chemical class Drugs Action sites

5HT3 antagonist

Ondansetron, Granisetron, Tropisetron

Aprepitant Dexamethasone Lorazepam, Diazepam Diphehydramine Metoclopramide

CTZ & peripheral 5HT3

CTZ substance-P Prostaglandin Sedative & anxiolytic Vestibular nucleus Dopamine antagonist

NK-1 antagonist Corticosteroid BZE Antihistamines Dopamine & 5HT3 receptor

Emetic potential High Moderate Low

Acute emesis 5HT3 + Dex + NK1 5HT3 + Dex Dex + MCP

Delayed emesis Dex + NK1 Dex Nil

Minimal

Nil

Nil

Antiemetics for radiation