Sorafenib for Patients with Hepatocellular Carcinoma and Child‐Pugh B Liver Cirrhosis: Lessons Learned from a Terminated Study. (23rd October 2019)

• Record Type: Journal Article
• Authors: Labeur, Tim A.; Achterbergh, Roos; Takkenberg, Bart; Van Delden, Otto; Mathôt, Ron; Klümpen, Heinz‐Josef
• Is Part Of: Oncologist. Volume 25:Number 9(2020)
• Page Start: e1274
• Page End: e1279
• Publication Date: 2019-10-23
• Subjects: Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2019-0718
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: Lessons Learned: Recruitment of patients with advanced hepatocellular carcinoma and Child‐Pugh B for sorafenib treatment and additional pharmacokinetic studies is challenging. Patients with Child‐Pugh B liver cirrhosis have high rates of cirrhosis‐related adverse events. Background: Few data are available on the pharmacokinetics (PK) of sorafenib in patients with advanced hepatocellular carcinoma (HCC) and Child‐Pugh B liver cirrhosis. This study aimed to explore the sorafenib PK and its relationship with efficacy and toxicity in these patients. Methods: Patients with advanced HCC and Child‐Pugh B7‐8 liver function were prospectively recruited at a tertiary center. Adverse events (AEs), progression‐free survival (PFS), and overall survival (OS) were recorded. Patients received a starting dose of 200 b.i.d. with toxicity‐adjusted dose escalation to a target dose of 400 mg b.i.d. with PK sampling at fixed time points. Results: Between May 2014 and March 2017, 12 patients were screened, of whom 7 progressed to a terminal stage during the screening ( n = 6) or shortly after recruitment ( n = 1). The five included patients had median PFS of 3.8 months (range, 1.7–10.8) and OS of 7.4 months (range, 1.7–25.8). Three patients had severe AEs and one patient had a partial response with an OS of 25.8 months. In 2017, the trial was aborted for lack of accrual. Conclusion: Because of low accrual, no conclusion can be drawn on the sorafenib PK in patients with advanced HCC and Child‐Pugh B liver cirrhosis. The poor survival and frequent cirrhosis‐related AEs suggest limited benefit for most of these patients.