Ondansetron Cisplatin

Augments the antiemetic activity of the 5-HT3-receptor antagonist ondansetron and the corticosteroid dexamethasone and inhibits both the acute and delayed phases of cisplatin-induced emesis... 

Ondansetron antagonizes the action of serotonin at receptors in the upper gastrointestinal tract and in the chemoreceptor trigger zone of the central nervous system. Given intravenously (IV), it prevents vomiting completely for 24 h in 40% of patients treated with high doses (>100 mg/m2) of cisplatin and in 70 to 80% of patients treated with 50 to 100 mg/m2 of cisplatin or a combination of cyclophosphamide and doxorubicin. 

Metoclopramide (Reglan, and others) is both a serotonin- and dopamine-receptor antagonist. Given alone, it is less effective than TV ondansetron. Given concurrently with dexamethasone and either the antianxiety agent lorazepam (Ativan, and others) or the antihistamine diphenhydramine (Benadryl, and others), it can control emesis due to high-dose cisplatin (120 mg/m2) in older adults. One study in older patients, however, found metoclopramide, dexamethasone, and diphenhydramine less effective than IV ondansetron combined with dexamethasone in patients taking > 50 mg/m2... 

Even after an effective regimen for prophylaxis, nausea or vomiting can begin again or persist 24 h or more after chemotherapy, particularly with cisplatin. Concurrent use of oral dexamethasone (8 mg twice daily for 2 d, then 4 mg twice daily for 2 d) and oral metoclopramide (0.5 mg/kg four times daily for 4 d) has been effective for this condition. Ondansetron alone has not been effective for treatment of delayed emesis following high doses of cisplatin. 

Many chemotherapeutic regimens include cisplatin for 4 or 5 d. Concurrent intravenous ondansetron and dexamethasone in two studies prevented emesis in 58 and 66% of patients for the entire 5-d period (see Table 18.3). 

Manusirivithaya S, Chareoniam V, Isariyodom P, Sungsab D. Comparison of ondansetron-dexamethasone-lorazepam versus metoclopramide-dexamethasone-lorazepam in the control of cisplatin induced emesis. J Med Assoc Thai 2001 84(7) 966-72. 

Kwiatkowska M, Parker LA, Burton P, Mechoulam R (2004) A comparative analysis of the potential of cannabinoids and ondansetron to supress cisplatin-induced emesis in the Suncus murinus (house musk shrew). Psychopharmacology (Berl). 174 254-259... 

De Mulder PH, Seynaeve C, Vermorken JB, et al. Ondansetron compared with high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting A multicenter, randomized, double-blind, crossover study. Ann Intern Med 1990 113 834-840. 

Cisplatin Alkylating agent—crosslinks DNA strands Testicular, ovarian, bladder, lung CA Nausea, vomiting (use ondansetron) Nephrotoxicity (use amifostine) Neurotoxicity (deafness)... 

Ondansetron, a serotonin (5-HT3)-receptor antagonist (0.15 mg/kg IV with the first dose taken infused every 15 minutes before the start of chemotherapy), is used in the prevention of nansea and vomiting associated with initial and repeat conrses of emetogenic cancer chemotherapy, including high-dose cisplatin (see Figure 73). 

Some evidence su ests ondansetron may modestly affect the pharmacokinetics of cyclophosphamide and cisplatin but it does not appear to affect those of carmustine. Ondansetron did not affect the in vitro activity of epirubicin, bleomycin, cisplatin or es-tramustine. Cisplatin and fluorouracil do not affect the pharmacokinetics of ondansetron. In in vitro studies granisetron potentiated the cytotoxic effects of epirubicin, had an additive effect on bleomycin and estramustine activity and appeared not to affect the metabolism of docetaxel and paclitaxel. 

The pharmacokinetics of high-dose cyclophosphamide, cisplatin and carmustine in 23 patients given ondansetron, lorazepam and diphenhydramine as antiemetics were compared with those in 129 patients who received prochlorperazine instead of ondansetron. It was found that the AUCs of cyclophosphamide and cisplatin, but not that of carmustine, were significantly lower (by 15% and 19%, respectively) in the ondansetron group. Similarly, in another study, the pharmacokinetics of antineoplastics were analysed in 54 patients with breast cancer who were receiving high-dose cyclophosphamide, cisplatin and carmustine with lorazepam and ondansetron with or without prochlorperazine and com-... 

An in vitro study found that ondansetron did not affect the cytotoxic effects of bleomycin, epimbicin, estramnstine or cisplatin in fibroblasts and lung cancer cells. ... 

Behnam MotlaghP, HenrikssonR, GrankvistK. Interaction of tiie antiemetics ondansetron and graniselron widi die c3/totoxicity induced by irradiation, epirubicin, bleomycin, estramustine, and cisplatin in vitro. Acta Oncol (1995) 34, 871-5. 

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