No abstract

This study analyzed outcomes of systemic chemotherapy for advanced neuroendocrine carcinoma (NEC) of the digestive system. Clinical data from 258 patients with unresectable or recurrent NEC of the gastrointestinal tract (GI) or hepato-biliary-pancreatic system (HBP), who received chemotherapy, were collected from 23 Japanese institutions and analyzed retrospectively. Patients had primary sites in the esophagus (n = 85), stomach (n = 70), small bowel (n = 6), colorectum (n = 31), hepato-biliary system (n = 31) and pancreas (n = 31). Median overall survival (OS) was 13.4 months the esophagus, 13.3 months for the stomach, 29.7 months for the small bowel, 7.6 months for the colorectum, 7.9 months for the hepato-biliary system and 8.5 months for the pancreas. Irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) were most commonly selected for GI-NEC and HBP-NEC. For patients treated with IP/EP (n = 160/46), the response rate was 50/28% and median OS was 13.0/7.3 months. Multivariate analysis among patients treated with IP or EP showed that the primary site (GI vs HBP; hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35–0.97) and baseline serum lactate dehydrogenase levels (not elevated vs elevated; HR 0.65, 95% CI 0.46–0.94) were independent prognostic factors for OS, while the efficacy of IP was slightly better than for EP (HR 0.80, 95% CI 0.48–1.33; P = 0.389). IP and EP are the most common treatment regimens for NEC of the digestive system. HBP primary sites and elevated lactate dehydrogenase levels are unfavorable prognostic factors for survival. A randomized controlled trial is required to establish the appropriate chemotherapy regimen for advanced NEC of the digestive system. This study was registered at UMIN as trial number 000005176.

Purpose Clinical evidence demonstrating the effectiveness of systemic therapy for advanced salivary duct carcinoma (SDC) is lacking because of the disease’s rarity. We assessed the efficacy and toxicity of trastuzumab plus docetaxel in patients with locally advanced and/or recurrent or metastatic human epidermal growth factor receptor 2–positive SDC. Patients and Methods This was a single-center, single-arm, open-label, phase II study in Japan. The patients received trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks. Docetaxel 70 mg/m2 was administrated every 3 weeks. The primary end point was the overall response rate; the secondary end points included the clinical benefit rate, progression-free survival, overall survival, and toxicity. This study is registered with the University Hospital Medical Information Network Clinical Trials Registry (Identification No. UMIN000009437). Results Fifty-seven eligible patients with SDC were enrolled. The overall response rate was 70.2% (95% CI, 56.6% to 81.6%), and the clinical benefit rate was 84.2% (95% CI, 72.1% to 92.5%). Median progression-free and overall survival times were 8.9 months (95% CI, 7.8 to 9.9 months) and 39.7 months (95% CI, not reached), respectively. The most frequent adverse event was anemia (52 patients [91%]), followed by a decreased WBC count (51 patients [89%]) and neutropenia (50 patients [88%]). The most frequently observed grade 4 adverse event was a decreased neutrophil count (34 patients [60%]). Grade 3 febrile neutropenia was reported in eight patients (14%). No grade 2 or greater adverse events of heart failure or left ventricular ejection fraction decline to less than 50% occurred. Conclusion Our data show encouraging efficacy of trastuzumab plus docetaxel therapy in patients with human epidermal growth factor receptor 2–positive SDC, with a manageable toxicity profile.

BackgroundThere is no standard first-line chemotherapy for recurrent/metastatic (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC).Patients and methodsWe conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75 mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80 mg. Patients were treated until progressive disease or unacceptable toxicities.ResultsThirty-six eligible patients were enrolled. Thirty-three patients had RM disease and three patients had LA disease. The pathological diagnoses were salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients, 6%). The best overall response rate was 41.7% [n = 15, 95% confidence interval (CI), 25.5%–59.2%], the clinical benefit rate was 75.0% (n = 27, 95% CI, 57.8%–87.9%). The median progression-free survival was 8.8 months (95% CI, 6.3–12.3 months) and the median overall survival was 30.5 months (95% CI, 16.8 months to not reached). Additional analyses between treatment outcomes and clinicopathological factors or biomarkers including AR positivity, human epidermal growth factor receptor 2 status, and its complex downstream signaling pathway gene mutations showed no statistically significant differences. Elevated grade 3 liver transaminases and increased serum creatinine were reported in two patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide due to adverse event occurred in one patient.ConclusionThis study suggests that CAB has equivalent efficacy and less toxicity for patients with AR-positive RM or unresectable LA SGC compared with conventional chemotherapy, which warrants further study.Clinical Trial RegistrationUMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703