Mirtazapine plus granisetron and dexamethasone for carboplatin-induced nausea and vomiting in patients with thoracic cancers: A prospective multicenter phase II trial.

BACKGROUND: Mirtazapine blocks 5-hydroxytryptamine type (5-HT)2A, 5-HT2C, 5-HT3 and histamine H1 receptors, similarly to olanzapine. This study aimed to investigate the efficacy and safety of mirtazapine plus granisetron and dexamethasone for carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic cancers. METHODS: We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four institutions in Japan. Registered patients were moderately to highly emetogenic chemotherapy-naïve, and were scheduled to receive CBDCA at area under the curve (AUC) ≥ 4 mg/mL per minute. Patients received mirtazapine 15 mg/day orally at bedtime for four consecutive days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the delayed period (24-120 h). RESULTS: Between July 2022 and July 2023, 52 patients were enrolled, and 48 patients were evaluated. CR rates in the delayed (24-120 h), overall (0-120 h), and acute periods (0-24 h) were 83.3%, 83.3%, and 100%, respectively. No grade 3 or higher treatment-related adverse events were observed except for one patient who had grade 3 dry mouth as evaluated by Common Terminology Criteria for Adverse Events version 5.0. CONCLUSIONS: Prophylactic antiemetic therapy with mirtazapine plus granisetron and dexamethasone shows promising efficacy and an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic cancers receiving a CBDCA-based regimen at AUC ≥ 4 mg/mL per minute.

Early improvement in bowel wall thickness on transperineal ultrasonography predicts treatment success in active ulcerative colitis.

BACKGROUND: Bowel ultrasonography is a non-invasive imaging tool that can repeatedly monitor ulcerative colitis (UC) activity. AIM: This study aimed to determine whether early transabdominal or transperineal ultrasonography changes can predict subsequent clinical response to induction therapy in patients with UC. METHODS: This single-centre prospective study explored ultrasonographic predictors for clinical remission (patient-reported outcome-2 ≤ 1 with no rectal bleeding subscore) at week 8 in patients with active UC who underwent induction therapy, in comparison with faecal calprotectin and C-reactive protein (measured at baseline, week 1 and week 8). Predictive factors were assessed using multivariable regression models and receiver-operating-characteristic curve analysis. RESULTS: A total of 100 patients were analysed, of which 54 achieved remission at week 8. Baseline biomarker and ultrasonographic-parameter values were not predictive of remission. Contrastingly, change from baseline to week 1 in rectal bowel wall thickness measured using transperineal ultrasonography was an independent predictor of remission by week 8 (adjusted odds ratio is associated with a 1-mm decrease: 1.90 [95% confidence interval, 1.22-2.95]). In a subgroup analysis of the patients who did not achieve remission in 1 week, the predictive value of change in rectal bowel wall thickness remained high (AUC = 0.77 [95% confidence interval, 0.61-0.88]). CONCLUSION: Improvement in rectal bowel wall thickness measured using transperineal ultrasonography at week 1 predicts treatment success and potentially facilitates decision making during the early course of induction therapy in UC.

Transperineal ultrasound predicts endoscopic and histological healing in ulcerative colitis.

BACKGROUND: Transabdominal ultrasound is useful to assess inflammation in patients with ulcerative colitis (UC); however, the assessment of the rectum is challenging and a barrier for its widespread use. AIM: To evaluate if transperineal ultrasound is useful for predicting endoscopic and histological findings of the rectum in UC. METHODS: Fifty-three consecutive adults with UC who required colonoscopy were included and transperineal ultrasound was performed in combination with transabdominal ultrasound within a week before or after colonoscopy with rectal biopsy. Mayo endoscopic subscore (MES) ≤1 was defined as endoscopic healing and Geboes score <2.1, Robarts histopathology index ≤6, and Nancy index ≤1 were defined as histological healing. Limberg score and bowel wall thickness were recorded with transperineal ultrasound. Faecal calprotectin was also measured. RESULTS: Excellent correlation was confirmed between colonoscopy and transabdominal ultrasound in all segments except for the rectum. Rectal bowel wall thickness and Limberg score in transperineal ultrasound well correlated with rectal MES and histological indices. Bowel wall thickness ≤4 mm predicted endoscopic (Area under the curve [AUC] = 0.90) and histological (AUC = 0.87-0.89) healing. In multivariable logistic regression analysis, only bowel wall thickness in transperineal ultrasound was a significant independent predictor for rectal endoscopic and histologic healing (P < 0.05) and the predictability was better than faecal calprotectin. CONCLUSIONS: Transperineal ultrasound predicts endoscopic and histological healing of the rectum. The combination of transperineal ultrasound with transabdominal ultrasound visualises the entire colorectum and is an ideal modality for the treat-to-target strategy. Clinical Trials Registry number UMIN000033611 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000038323).