1. Acute onset: within 24 hours of initial administration of chemotherapy
2. Delayed onset: occurring 24 hours to several days after initial treatment
3. Anticipatory: emetic episodes are triggered by taste, odor sight, thoughts, or anxiety secondary to a history of poor response to antiemetic agents
4. Breakthrough: occurring despite prophylactic treatment
5. Refractory: occurring during subsequent cycles when antiemetics have failed in earlier cycles
Risk of CINV with Chemotherapy medications
5-HT3RAs (Receptor Antagonists)
- High therapeutic index for prevention of CINV, most effective antiemetics in the prophylaxis of acute CINV.
- Generally safe, with a favorable side effect profile (low grade headache, malaise, and constipation). High-dose (24-32mg) Ondansetron appears to be more effective
- Some literature reports suggest a potential link between 5-HT3 receptor antagonists and the serotonin syndrome, QTc prolongation esp with a single IV dose of 32mg
- Steroids can be effective when administered as a single agent in patients receiving chemotherapy of low emetic potential. Most beneficial, when used in combination with other antiemetic agents.
- When corticosteroids are administered with aprepitant, doses should be reduced by half.
- Aprepitant is the first representative of this new group that blocks the NK1 receptor in the brainstem emetic center and gastrointestinal tract
- Aprepitant is a moderate inhibitor of CYP3A4; therefore, the dexamethasone dose has to be reduced if used concomitantly.
- In the past, metoclopramide was used alone or in combination with a corticosteroids
- Now, it is reserved for those who are intolerant to 5-HT3RAs or steroids
- May cause extrapyramidal side effects including acute dystonic reactions, akathisia
- An atypical antipsychotic drug with potential antiemetic properties because of its action at multiple receptor sites implicated in the control of nausea and vomiting.
- Used in certain circumstances, to cut anxiety and risk of anticipatory CINV or in patients with refractory and breakthrough emesis.
- Possess beneficial side effects (sedation, euphoria) in addition to weak antiemetic efficacy but usefulness is limited by the high incidence of toxic effects, such as dizziness and hallucinations.
- Advised in patients intolerant or refractory to 5-HT3RAs or steroids and aprepitant.
First Line for CINV - 5HT3 Antagonists, Steroids, NK1RA
Adjuncts - Benzodiazepines, D2 RA, Olanzapine, Anti-Histaminics, Cannabinoids
- Jordan K, Sippel C, Schmoll HJ. Guidelines for antiemetic treatment of chemotherapy-induced nausea and vomiting: past, present, and future recommendations. The oncologist. 2007 Sep 1;12(9):1143-50.
- WHO Pharmaceuticals newsletter. Ondansetron and serotonin syndrome. 2012; 3:16.
- Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT. Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuro psychopharmacology. 1996 Feb 29;14(2):87-96.
- WarrDG, HeskethPJ, GrallaRJetal. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in pa- tients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol 2005;23:2822–2830.
- Hesketh, Paul J. "Chemotherapy-induced nausea and vomiting." New England Journal of Medicine 358.23 (2008): 2482-2494.