ABSTRACT
BACKGROUND: In Japan and South Korea, transarterial chemoembolisation (TACE) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown effective and safe in patients with advanced HCC. This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE. METHODS: Patients (n=458) with unresectable HCC, Child-Pugh class A cirrhosis and ≥25% tumour necrosis/shrinkage 1-3 months after 1 or 2 TACE sessions were randomised 1:1 to sorafenib 400mg bid or placebo and treated until progression/recurrence or unacceptable toxicity. Primary end-point was time to progression/recurrence (TTP). Secondary end-point was overall survival (OS). FINDINGS: Baseline characteristics in the two groups were similar; >50% of patients started sorafenib>9 weeks after TACE. Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months, respectively (hazard ratio (HR), 0.87; 95% confidence interval (CI), 0.70-1.09; P=0.252). HR (sorafenib/placebo) for OS was 1.06 (95% CI, 0.69-1.64; P=0.790). Median daily dose of sorafenib was 386 mg, with 73% of patients having dose reductions and 91% having dose interruptions. Median administration of sorafenib and placebo was 17.1 and 20.1 weeks, respectively. No unexpected adverse events were observed. INTERPRETATION: This trial, conducted prior to the reporting of registrational phase III trials, found that sorafenib did not significantly prolong TTP in patients who responded to TACE. This may have been due to delays in starting sorafenib after TACE and/or low daily sorafenib doses.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzenesulfonates/administration & dosage , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Liver Neoplasms/therapy , Pyridines/administration & dosage , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Combined Modality Therapy , Disease Progression , Double-Blind Method , Female , Humans , Intention to Treat Analysis , Japan , Male , Middle Aged , Niacinamide/analogs & derivatives , Phenylurea Compounds , Republic of Korea , Sorafenib , Survival Analysis , Treatment OutcomeABSTRACT
The current study evaluated efficacy of the intravenous calcium injection test as a new diagnostic approach to clarify the existence of gastrinoma, which often goes undetected with routine testing. Twenty-six patients with hypergastrinemia were studied. For the calcium injection test, blood samples were taken from 12 patients with hypergastrinemia (HG), and three healthy volunteers, and one patient with nonfunctioning endocrine tumor in the pancreas (control). We compared results of the calcium injection test with those of the secretin test and the selective arterial secretagogue injection (SASI) test. The SASI test with secretin was performed in 24 of 26 patients with hypergastrinemia, including 22 of 24 patients with Zollinger-Ellison syndrome (ZES). Accuracy in the diagnosis of tumor localization by the SASI test was 95% (21 of 22) in ZES patients. The secretin test was negative in 3 of 21 patients with ZES (14%). Either the secretin test or the SASI test was positive in 22 of 23 patients (96%). The calcium injection test was administered to 12 patients in the HG group and 4 controls. The HG group showed significantly higher serum gastrin levels than those of the control group in the calcium injection test. Eight of 10 ZES patients (80%) had a positive calcium injection test. We could diagnose gastrinomas in 100% of ZES patients by either the calcium injection test or the secretin test. We have thus confirmed the efficacy of the intravenous calcium injection test in the diagnosis of gastrinoma. The calcium injection test could become an adjunct in the diagnosis of gastrinoma, which often goes undetected with routine testing.