Efficacy of Prophylactic Treatment for Oxycodone-Induced Nausea and Vomiting Among Patients with Cancer Pain (POINT): A Randomized, Placebo-Controlled, Double-Blind Trial

Abstract

Background: Although opioid-induced nausea and vomiting (OINV) often result in analgesic undertreatment in patients with cancer, no randomized controlled trials have evaluated the efficacy of prophylactic antiemetics for preventing OINV. We conducted this randomized, placebo-controlled, double-blind trial to evaluate the efficacy and safety of prophylactic treatment with prochlorperazine for preventing OINV.

Materials and methods: Cancer patients who started to receive oral oxycodone were randomly assigned in a 1:1 ratio to receive either prochlorperazine 5 mg or placebo prophylactically, given three times daily for 5 days. The primary endpoint was the proportion of patients who had a complete response (CR) during the 120 hours of oxycodone treatment. CR was defined as no emetic episode and no use of rescue medication for nausea and vomiting during 5 days. Key secondary endpoints were the proportion of patients with emetic episodes, proportion of patients with moderate or severe nausea, quality of life, and proportion of treatment withdrawal.

Results: From November 2013 through February 2016, a total of 120 patients were assigned to receive prochlorperazine (n = 60) or placebo (n = 60). There was no significant difference in CR rates (69.5% vs. 63.3%; p = .47) or any secondary endpoint between the groups. Patients who received prochlorperazine were more likely to experience severe somnolence (p = .048).

Conclusion: Routine use of prochlorperazine as a prophylactic antiemetic at the initiation of treatment with opioids is not recommended. Further research is needed to evaluate whether other antiemetics would be effective in preventing OINV in specific patient populations.

Implications for practice: Prophylactic prochlorperazine seems to be ineffective in preventing opioid-induced nausea and vomiting (OINV) and may cause adverse events such as somnolence. Routine use of prophylactic prochlorperazine at the initiation of treatment with opioids is not recommended. Further research is needed to evaluate whether other antiemetics would be effective in preventing OINV in specific patient populations.

Keywords: Antiemetics; Cancer pain; Opioid‐induced nausea and vomiting; Oxycodone; Prochlorperazine; Prophylaxis.

Figure 1.

CONSORT 2010 Flow Diagram. Screening, randomization, and follow‐up.

Figure 2.

Time to first emetic episode and first rescue antiemetic medication. Time‐to‐event endpoints were analyzed using Kaplan‐Meier methods and were tested using the log‐rank test. (A): Time to first emetic episode. (B): Time to first rescue antiemetic medication. Abbreviations: A, Prochlorperazine group; B, Placebo group; h, hours.

Figure 3.

Forest plots of complete response Abbreviations: CI, confidence interval; NRS, numeric rating scale; OR, odds ratio; PS, performance status.