Midazolam for acute emesis refractory to dexamethasone and granisetron after highly emetogenic chemotherapy: a phase II study
To assess whether the addition of midazolam to dexamethasone and granisetron could ameliorate the refractory acute nausea and/or vomiting caused by a highly emetogenic platinum-based chemotherapy. Enrolled in the study were 30 consecutive adult patients with refractory acute emesis. Nausea and vomiting were assessed by physicians and graded according to the NCI common toxicity criteria. Nausea was further self-assessed by patients using a visual analogue scale. Statistical analysis was performed by nonparametric tests. With the introduction of midazolam, 73% of patients had a reduction of at least one grade in nausea and vomiting intensity in comparison with the previous cycle of chemotherapy. From the second cycle, six patients (23%) had complete control of acute vomiting, a benefit that usually persisted in the subsequent cycles. Five more patients achieved complete control of acute vomiting during the third course; this effect persisted in the subsequent courses as well. The average relative reduction in acute nausea and vomiting grade from the first to the second course was 48% (95% CI 34–62%) and 48% (95% CI 31–65%), respectively. A significant difference in acute nausea and vomiting over all the six courses of chemotherapy administered was recorded (Friedman ANOVA, P <0.0001). Comparing each course with any subsequent course, a significant reduction in acute nausea and vomiting was observed between the first and second course, the first and third course, and the first and fourth course. Our results suggest that midazolam may be a useful adjunct to standard antiemetic drugs for patients receiving highly emetogenic cisplatin-based chemotherapy. A randomized trial is warranted to confirm these results.