Dexamethasone and high dose metoclopramide: efficacy in controlling cisplatin induced nausea and vomiting.

Allan, S G; Cornbleet, M. A.; Warrington, P. S.; Golland, I. M.; Leonard, Robert; Smyth, J N

doi:10.1136/bmj.289.6449.878-a

Cited by 95 publications

(28 citation statements)

References 3 publications

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“…The useful anti-emetic activity of dexamethasone both in non-cis-platinum and cis-platinum containing chemotherapy-induced vomiting (Cassileth et al, 1983;Allan et al, 1984) is unexplained. The latter study showed that dexamethasone could shorten the prolonged nausea associated with cis-platinum administration.…”

Section: Discussionmentioning

confidence: 99%

“…The correlation of prolonged gastrointestinal symptoms with intestinal mucosal toxicity in patients receiving platinate compounds is unproven and human intestinal biopsies, in patients receiving these compounds, may help in solving this issue. Where efficacy is established the use of these platinum analogues will reduce the morbidity of cancer chemotherapy but where cis-platinum continues to be used then amelioration of associated gastrointestinal symptoms may be achieved by effective anti-emesis (Allan et al, 1984) or potentially by antidoting cis-platinum intestinal cytotoxicity (Allan et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

“…Recently dexamethasone has been shown to enhance significantly the efflcacy of high dose metoclopramide and to reduce the duration of subsequent nausea (Allan et al, 1984). The mechanism of action of dexamethasone as an anti-emetic is not known.…”

mentioning

confidence: 99%

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Small intestinal mucosal toxicity of cis-platinum – comparison of toxicity with platinum analogues and dexamethasone

Allan¹,

Smyth²

1986

Br J Cancer

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Summary Cis-platinum causes profound gastrointestinal symptoms in patients and these may persist for many days after drug administration. Gut mucosal toxicity may be a factor in the pathogenesis of such prolonged nausea, vomiting and anorexia. The effects of cis-platinum on mouse ileal mucosal architecture, villus epithelial cell influx and disaccharidase activity are described in comparison with dhe effects of two platinum analogues, CBDCA and CHIP. In addition the effect of dexamethasone, a useful drug in the palliation of cis-platinum-induced emesis, in combination with cis-platinum is described.Cis-platinum, CBDCA and CHIP cause profound reduction in crypt cell production rate (CCPR) and thus villus epithelial cell influx within hours of administration leading to villus stunting and diminished function. CBDCA showed the least profound effect with early rebound in CCPR by day 3. Cis-platinum and CHIP were roughly equitoxic to ileal crypts with rebound in CCPR being delayed until day 7. Similarly, CBDCA caused least reduction in disaccharidase activity with cis-platinum and CHIP being equitoxic. The addition of dexamethasone had no protective effect on the effects of cis-platinum on murine ileal mucosa and mice given the combination chronically had no weight gaii over 18 weeks, their weight paralleling those receiving cisplatinum alone.The platinate compounds have differing degrees of intestinal mucosal toxicity but no direct inference can be drawn in respect to the clinical situation where CBDCA causes less gastrointestinal symptomatology than CHIP but where both cause less than cis-platinum. Dexamethasone does not act by mucosal protection to provide its useful effects in prolonged cis-platinum-induced gastrointestinal symptoms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Small intestinal mucosal toxicity of cis-platinum – comparison of toxicity with platinum analogues and dexamethasone

Allan¹,

Smyth²

1986

Br J Cancer

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“…Controlled trials have shown that this combination is superior to metoclopramide, given alone, for the control of acute cisplatin-induced emesis. For example Allan et al (36) found that in a randomized, double-blind cross-over trial, a complete response was achieved in 43",, of courses treated with metoclopramide ( 5 mg/kg every 2 h) plus dexamethasone (20 mg i.v. before chemotherapy), compared to 26",, of courses treated with metoclopramide alone.…”

Section: Combznation Anti-emetic Therapy Using Conventional Anti-emeticsmentioning

confidence: 99%

“…High-dose metoclopramide in combination with dexamethasone has been studied extensively (36,37). Controlled trials have shown that this combination is superior to metoclopramide, given alone, for the control of acute cisplatin-induced emesis.…”

Section: Combznation Anti-emetic Therapy Using Conventional Anti-emeticsmentioning

confidence: 99%

Advances in the Management of Cytotoxic Drug-Induced Nausea and Vomiting

Freeman¹,

Cullen

1991

J Clin Pharm Ther

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Antiemetic control and prevention of side effects of anti-cancer therapy with lorazepam or diphenhydramine when used in combination with metoclopramide plus dexamethasone. A double-blind, randomized trial

Kris

Gralla

Clark

et al. 1987

Cancer

133

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Combinations of metoclopramide and dexamethasone given intravenously control vomiting caused by high doses of cisplatin. Lorazepam and diphenhydramine are useful adjuncts to antiemetics. In a double-blind trial, 120 patients receiving high-dose cisplatin (120 mg/m2) for the first time were randomly assigned to receive either lorazepam (1.5 mg/m2) or diphenhydramine (50 mg) intravenously, 45 minutes prior to cisplatin. In addition, all patients received intravenous dexamethasone (20 mg) 40 minutes prior to chemotherapy along with metoclopramide (3 mg/kg) 30 minutes before and 90 minutes after cisplatin. Patients were directly observed in the hospital after cisplatin administration and completed a subjective assessment questionnaire. Overall, 60% of patients experienced no vomiting, and 83% had two or fewer emetic episodes during the study. There were no significant differences in objective antiemetic control between the two regimens. Only 3% of patients receiving lorazepam experienced treatment-related restlessness as opposed to 19% given diphenhydramine (P = 0.007). Less recall of chemotherapy administration (P less than 0.001), more sedation (P = 0.003), and transient enuresis while sedated (P = 0.0002) were characteristic of patients receiving lorazepam. Patient-generated ratings revealed less anxiety (P = 0.0001) for those individuals given the lorazepam-containing combination. Both regimens were well accepted, with 89% of patients receiving the lorazepam combination and 83% of those given the diphenhydramine regimen wishing to receive the same drugs in the future. Some degree of delayed vomiting occurred in 85% of patients during the 4-day period following this study. During the time that patients are at the greatest risk for emesis, the 24 hours immediately following cisplatin, three drug antiemetic combinations of either lorazepam or diphenhydramine with metoclopramide plus dexamethasone stopped cisplatin-induced emesis for the majority of patients and lessen other treatment-related side effects. Less restlessness and anxiety were observed among individuals receiving the lorazepam-containing combination.

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Dexamethasone and high dose metoclopramide: efficacy in controlling cisplatin induced nausea and vomiting.

Cited by 95 publications

References 3 publications

Small intestinal mucosal toxicity of cis-platinum – comparison of toxicity with platinum analogues and dexamethasone

Small intestinal mucosal toxicity of cis-platinum – comparison of toxicity with platinum analogues and dexamethasone

Advances in the Management of Cytotoxic Drug-Induced Nausea and Vomiting

Antiemetic control and prevention of side effects of anti-cancer therapy with lorazepam or diphenhydramine when used in combination with metoclopramide plus dexamethasone. A double-blind, randomized trial

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