Identification of Factors Associated With Clinically Problematic Hiccups in Male Patients Receiving Cisplatin-based Treatment With Dexamethasone and Aprepitant: A Subgroup Analysis

Background/Aim: Hiccups frequently occur during cisplatin (CDDP)-based treatment, and dexamethasone and neurokinin-1 receptor inhibitors may also induce these symptoms. We have previously reported that male sex is a significant risk factor for clinically problematic hiccups in patients receiving CDDP-based chemotherapy with these antiemetics. This study aimed to further evaluate factors associated with the symptoms in male patients receiving CDDP, dexamethasone, and aprepitant through a subgroup analysis. Patients and Methods: Male patients with thoracic cancer who received their first cycle of CDDP-based treatment (≥75 mg/m2) in combination with dexamethasone, palonosetron, and aprepitant (n=186) were retrospectively evaluated. The primary endpoint was the identification of factors associated with grade ≥2 hiccups during the first cycle. Results: The incidence of grade ≥2 hiccups was 46.8%, while the overall incidence of hiccups of any grade was 60.8%, including 8.1% grade 3 cases. The median time to symptom onset was two (range=1-5) days, and the median duration was two (range=1-12) days. Most patients (97.7%) received metoclopramide as first-line treatment, with an efficacy rate of 55.3%. Efficacy rates were 76.1% for baclofen, 86.4% for chlorpromazine, and 50.0% for Shakuyaku-Kanzo-To. Multivariable logistic regression analysis showed that hypoalbuminemia and concomitant bevacizumab use were significant risk factors for grade ≥2 hiccups [adjusted odds ratio (95% confidence interval)=2.53 (1.06-6.03), p=0.04; and 4.11 (1.26-13.38), p=0.02, respectively]. Conclusion: Hypoalbuminemia and concomitant bevacizumab use are significant risk factors for clinically problematic hiccups in male patients receiving CDDP-based treatment with dexamethasone and aprepitant for thoracic cancer.