Chemotherapy-Induced Emesis

The following overview is limited to control of emesis induced by cancer chemotherapy and presents more important developments in the last decade. The reader is referred to more extensive reviews and monographs on this subject [30, 37, 122-126]. 

Tonato M, Clark-Snow RA, Osoba D, Del Favero A, Ballatori E, Borjeson S. Emesis induced by low or minimal emetic risk chemotherapy. Support Care Cancer 2005 13(2) 109-11. 

Niiranen A, Mattson K (1985) A cross-over comparison of nabilone and prochlorperazine for emesis induced by cancer chemotherapy. Am J Clin Oncol 8 336-340... 

The Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer (2006) Prevention of chemotherapy- and radiotherapy-induced emesis results of the Perugia International Antiemetic Consensus Conference. Ann Oncol 17 20-28... 

Dexamethasone has been used successfully in the management of chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV), either as a single agent or in combination with selective serotonin reuptake inhibitors (SSRIs). For CINV, dexamethasone is effective in the prevention of both cisplatin-induced acute emesis and when used alone or in combination for the prevention of delayed nausea and vomiting associated with CINV. 

The present review covers progress in medical chemistry, basic mechanisms of emesis, role of serotonergic mechanism, and treatment of cancer-chemotherapy-induced emesis. 

The abdominal vagus and sympathetic nerves are the most important afferent inputs involved in vomiting induced by chemotherapy and radiation [31]. The input from vestibular nerves and the cerebellum plays an important role in the motion disease [52]. The afferent inputs from vagal, trigeminal and glossopharyngeal nerves terminate eventually in the nucleus solitarius tract located in the medulla oblongata which has neuronal connections with other medullary areas involved in emesis, for example, area postrema [53]. 

It had been reported that 5-HT and 2-Me-5-HT released DA in striatal slices [112]. The functional importance of this response is unknown, because the D2-dopamine antagonists are not efficient antiemetics against radiation- or chemotherapy-induced emesis. 

Chapter 7 outlines the basic mechanism and treatment of emesis, and in particular, that induced by chemotherapy of cancer. Finally, the chemistry, pharmacology and clinical applications of antagonists of the platelet-activating factor (PAF), an important mediator of many physiological and pathological conditions, are reviewed in Chapter 8. 

THC is effective in several chemotherapy regimens, including methotrexate and the doxorubicin/cyclophosphamide/fluorouracil combination. Cisplatin treatment, however, is more resistant. Side effects of THC are generally well tolerated, and use may be limited in the elderly or with higher doses. Nabilone is a synthetic cannabinoid that is more effective than prochlorperazine in chemotherapy-induced emesis, including cisplatin. Its side effects are similar to THC. Levonantradol is another synthetic cannabinoid with antiemetic effects, and may be administered orally or intramuscularly. The side effect of dysphoria may limit its use. 

Reddy, G.K., Gralla, R.J. and Hesketh, P.J., Novel neurokinin-1 antagonists as antiemetics for the treatment of chemotherapy-induced emesis. Support. Cancer Ther., 2006, 3, 140-142. 

Prevention of chemotherapy-induced emesis - For doses in excess of 10 mg, dilute injection in 50 ml of a parenteral solution (Dextrose 5% in Water,... 

Children Not recommended for AIDS-related anorexia in children because it has not been studied in this population. Dosage for chemotherapy-induced emesis is the same as in adults. Use caution in children because of the psychoactive effects. 

Prevention of chemotherapy-induced emesis Infuse slowly IV over not less than 15 minutes, 30 minutes before beginning cancer chemotherapy repeat every 2 hours for 2 doses, then every 3 hours for 3 doses. 

Chemotherapy-induced emesis IV 0.15 mg/kg 3 times a day beginning 30 minutes before chemotherapy or 0.45 mg/kg once daily or 8-10 mg 1 -2 times/day or 24-32 mg once daily. PO (Highly emetogenic) 24 mg 30 minutes before start of chemotherapy. (Moderately emetogenic) 8 mg q 12h beginning 30 minutes before chemotherapy and continuing for 1 -2 days after completion of chemotherapy. 

Pollard et alP from Merck required both enantiomers of 3,5-bistrifluoro-methylphenyl ethanol since the (R)-enantiomer can be incorporated into Merck s orally active NKl receptor antagonist for the treatment of chemotherapy induced emesis, while the (5)-enantiomer is used as a chiral synthon for a number of antagonists which the same company currently have under clinical evaluation. Using proteins from a library of commercially available alcohol dehydrogenases both enantiomers were obtained with ees of 99% (Figure 1.40). 

These are used routinely in conjunction with 5-HT3 antagonists in the management of chemotherapy-induced emesis, and more... 

Several nonpeptide NKi receptor antagonists have been developed. These compounds are highly selective and orally active, and enter the brain. Recent clinical trials have shown that these antagonists may be useful in treating depression and other disorders and in preventing chemotherapy-induced emesis. The first of these to be approved for the prevention of chemotherapy-induced nausea and vomiting is aprepitant (see Chapter 62). 

Ondansetron, other 5-HT3 antagonists 5-HT3 blockade in gut and CNS with shorter duration of binding than alosetron Extremely effective in preventing chemotherapy-induced and postoperative nausea and vomiting First-line agents in cancer chemotherapy also useful for postop emesis Usually given IV but orally active in prophylaxis. 4-9 h duration of action very low toxicity but may slow colonic transit... 

Antihistaminics Moderate efficacy in motion sickness and chemotherapy-induced emesis ... 

Olver IN. Update on anti-emetics for chemotherapy-induced emesis. Intern Med J. 2005 35 478-481. 

Ondansetron, granisetron, topisetron, and batanopride are antagonists of the 5HT3 receptor, and are considered effective in controlling cancer-chemotherapy-induced emesis. Clozapine, an effective antipsychotic agent (neuroleptics) with little or no extrapyramidal... 

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