End-of-life care

Haloperidol still first line drug for nausea in cancer

Low-dose haloperidol should be considered the first-line agent in cancer patients with ongoing nausea that is not related to their anticancer treatment, Australian researchers say.

A randomised-controlled trial of methotrimeprazine versus haloperidol in 11 palliative care sites around Australian found similar response rates between the two drugs.

The trial involved 121 adult cancer patients with average nausea scores of ≥3 on a 0-10 numerical rating scale, and who were able to tolerate oral medications.

They were randomised to either 1.5mg haloperidol or 6.25mg methotrimeprazine daily – doses which could be doubled on review after 24 hours. Oral metoclopramide 10mg, or domperidone in cases of intolerance, was available as rescue medication.

The study found the response to treatment at 72 hours – at least a two-point reduction in average nausea scores – was 75% with haloperidol and a statistically similar 63% with methotrimeprazine (p=0.18).

Patients in both arms of the study were significantly less distressed by their nausea at 72 hours compared to baseline.

Similar numbers of patients in each group had been prescribed higher doses at 72 hours (29% with haloperidol v 31% with methotrimeprazine) and episodes of vomiting reduced by about half.

Rescue doses of metoclopramide or domperidone were given in about 40% of patients.

Side effects were minimal, however patients on methotrimeprazine reported more drowsiness at 72 hours compared to baseline.

The researchers, including Professor Janet Hardy who leads the Palliative Care Research Group at Mater Research in Brisbane, said they have not yet found any drug that is superior to regular, low-dose haloperidol in this setting.

“This suggests that the newer, and often more expensive agents unlicensed for this indication (such as ondansetron, olanzapine as well as methotrimeprazine) should only be used second line and preferably within a monitored or trial context in the palliative care setting until further data are available.”

“Although there is a temptation to use new, more expensive agents in this setting, their benefit over and above haloperidol has yet to be established.”

They added it was now difficult to justify the use of a placebo in any controlled clinical trials of patients with nausea unrelated to chemotherapy or radiotherapy.

“Future studies should consider regular haloperidol as the standard comparator,” the researchers said.

“The optimal dose of haloperidol must be determined however, as it may be lower than that used in this study.”

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