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5-HT3 receptor antagonists for chemotherapy-induced vomiting

 

Clinical bottom line

5-HT3 receptor antagonists are better than conventional antiemetic therapy for reducing vomiting in the first 24 hours of chemotherapy, and probably later. About 50% of patients vomit with conventional therapy, 40% with 5-HT3 receptor antagonists and 25% with a combination of 5-HT3 receptor antagonist and dexamethasone.


Reference

IT Jantunen et al. An overview of randomised studies comparing 5-HT3 receptor antagonists to conventional anti-emetics in the prophylaxis of acute chemotherapy-induced vomiting. European Journal of Cancer 1997 33: 66-74.

Review

Searching was done in April 1996 using Medline. No description of the search strategy is given, nor were any other databases searched, and trials used were only in English.

Inclusion criteria were randomised comparisons of 5-HT3 receptor antagonist and any other antiemetic therapy for adult patients receiving cytotoxic chemotherapy. Final acceptance was on the criteria of a randomised trial, a 5-HT3 receptor antagonist in at least one arm, possible to characterise emetogenicity of chemotherapy, number of patients in each arm and number vomiting in the first 24 hours given.

Results

They found 27 reports of 28 trials, and added two abstracts.There were a number of possible comparisons in the first 24 hours, and one for the first 4-5 days (Table 1).

Table 1: Comparisons between 5-HT3 receptor antagonists and other treatments

Vomiting/Total

Treatment

Comparator

Number of trials

with treatment

with comparator

Relative risk (95%CI)

NNT (95%CI)

Over 24 hours
5HT3 alone or with dexamethasone Cocktail based on high-dose metoclopramide

15

531/1320

674/1314

0.79 (0.63 to 0.86)

9 (7 to 14)

5HT3 alone or with dexamethasone Conventional antiemetic treatment

11

293/924

450/924

0.66 (0.59 to 0.74)

6 (5 to 8)

5HT3 with dexamethasone 5HT3 alone

11

272/1102

414/1017

0.58 (0.51 to 0.66)

7 (5 to 8)

Over 4-5 days
5HT3 alone or with dexamethasone Conventional antiemetic treatment

4

80/169

123/160

0.62 (0.52 to 0.74)

3.3 (2.5 to 5.1)

Over the first 24 hours 5-HT3 receptor antagonists alone or in combination with dexamethasone were superior to cocktails based on high-dose metoclopramide or conventional anti-emetic regimens. 5-HT3 receptor antagonist with dexamethasone was superior to 5-HT3 receptor antagonist alone, with consistent results between trials (Figure 1).

Figure 1: L'Abbé plot of percentage of patients vomiting in the first 24 hours with 5-HT3 receptor antagonist plus dexamethasone against 5-HT3 receptor antagonist alone.


 

Over the first 4-5 days 5-HT3 receptor antagonists alone or in combination with dexamethasone were superior to conventional anti-emetic regimens.

The percentage of patients who vomited was higher in with high-dose metoclopramide and conventional antiemetic therapy (at about 50%), than with 5-HT3 receptor antagonist alone (about 40%) and 5-HT3-antagonist plus dexamethasone (about 25%).

Figure 2: Percentage of patients vomiting in the first 24 hours with different treatments (95% confidence interval)


 

Comment

This is an interesting and useful review that actually has many of the details that one would want to see, but rather well hidden. The trials are described in some detail, and the results clear.