Dataset Information

Clinical Impact of Vitamin K Dosing on Sorafenib Treatment for Hepatocellular Carcinoma.

ABSTRACT: Background: Some researchers have suggested that vitamin K enhances the antitumor effect of sorafenib for hepatocellular carcinoma (HCC) in vitro and in vivo. In this study, we examined the clinical impact of vitamin K dosing for sorafenib treatment. Methods: Twenty-nine out of 65 patients treated with sorafenib for HCC were simultaneously dosed with vitamin K. We retrospectively investigated progression-free survival (PFS) and overall survival (OS) in the vitamin K-dosed group and sorafenib alone group. We also examined the changes in serum des-γ-carboxy prothrombin (DCP) levels, which vitamin K is involved with. Results: The median PFS was prolonged in the sorafenib + vitamin K group compared with the sorafenib alone group (6.0 months and 2.0 months, respectively; P<0.001, hazard ratio〔HR〕: 0.25). The median OS was also significantly extended (12.5 months vs. 10.0 months; P=0.009, HR: 0.47). Despite suppressed tumor growth, serum DCP levels had increased in cases of disease-controlled patients in the sorafenib alone group 8 weeks after the beginning of treatment, (2.28±0.91 to 2.64±1.03, P= 0.048). In contrast, the serum DCP levels of the sorafenib + vitamin K group had declined both in patients with controlled disease and in patients with progressive disease (1.97±0.57 to 1.29±0.28, P=0.002 and 2.90±1.32 to 1.78±0.53, P=0.034, respectively). Conclusions: To the best of our knowledge, this is the first clinical report showing enhanced antitumor action of sorafenib by vitamin K. Our clinical findings suggest that vitamin K may have the synergistic effect by suppressing production of DCP, a tumor growth and angiogenesis factor.

SUBMITTER: Haruna Y

PROVIDER: S-EPMC5559959 | biostudies-other | 2017

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:Patients with hepatocellular carcinoma waiting for liver transplantation are commonly treated with locoregional treatments, such as TACE and ablation, to prevent tumor progression and dropout and to improve long-term outcome after transplantation. We wanted to prospectively assess feasibility of systemic antitumor treatment with sorafenib as neoadjuvant treatment for hepatocellular carcinoma while waiting for liver transplantation, evaluating tolerability, toxicity and posttransplant morbidity. We also wanted to evaluate perfusion CT parameters to assess tumor properties and response early after start of sorafenib treatment in patients with early hepatocellular carcinoma. METHODS:Twelve patients assigned for liver transplantation due to hepatocellular carcinoma, within the UCSF and who fulfilled other criteria, were included January 2012-August 2014. After baseline evaluation, sorafenib treatment was started. Treatment was evaluated by perfusion CT at 1, 4 and 12 weeks and thereafter every 8 weeks. Toxicity and quality of life was assessed at 1 and 4 weeks and every 4 weeks thereafter during treatment. Treatment was stopped when patients were prioritized on the transplantation waiting list or when intolerable side effects or tumor progress warranted other treatments. Posttransplant morbidity after 90 days was registered according to Clavien-Dindo. RESULTS:Baseline perfusion CT parameters in the tumors predicted the outcome according to RECIST/mRECIST at three months, but no change in CTp parameters was detected as a result of sorafenib. Sorafenib as neoadjuvant treatment was associated with intolerability and dose reductions. Therefore the prerequisites for evaluation of the sorafenib effect on both CT parameters and tumor response were impaired. CONCLUSIONS:This study failed to show changes in CTp parameters during sorafenib treatment. Despite the curative treatment intention, tolerability of neoadjuvant sorafenib treatment before liver transplantation was inadequate in this study. TRIAL REGISTRATION:EudraCT number: 2010-024306-36 (date 2011-04-07).

Project description:The prognosis for hepatocellular carcinoma (HCC) is dependent upon tumour stage, performance status (PS), severity of underlying liver disease, and the availability of appropriate therapies. The unavailability of sorafenib may have a significantly adverse effect on the prognosis of UK patients with advanced HCC. During the study period, access to sorafenib was at the discretion of local health funding bodies, a process that may delay or deny access to the drug and that remains in place for Wales, Scotland, and Northern Ireland. Here, we attempt to address the impact of this system on patients with advanced HCC in the United Kingdom.This is a retrospective study performed in the two largest specialist hepatobiliary oncology units in the United Kingdom. Funding applications were made to local funding bodies for patients with advanced HCC for whom sorafenib was considered appropriate (advanced HCC not suitable for loco-regional therapies, compensated chronic liver disease, PS 0-2).A total of 133 applications were made, of which 57 (43%) were approved and 76 (57%) declined. Demographics and prognostic factors were balanced between the two groups. This cohort had a number of adverse prognostic features: patients were predominantly PS 1-2; the majority had multifocal disease with the largest lesion being >5 cm; and macroscopic vascular invasion, metastases, and AFP >,000 ng ml(-1), were each present in one-third of cases. The median time from application to funding decision was 17 days (range 3-260 days). For the primary 'intention-to-treat' analysis, median overall survival was 4.1 months when funding was declined, and 9.5 months when funding was approved (hazard ratio (HR) 0.48; 95% CI 0.3186-0.7267; P=0.0005).These data support the use of sorafenib for patients with advanced HCC as an effective intervention. In the United Kingdom, this applies to a relatively small group of patients, estimated to total ∼800 per year who, unfortunately, do not survive long enough to themselves lobby for the availability of this drug. These data provide a comparison of sorafenib with supportive care and demonstrate the potential detrimental impact on patient outcomes of rationing health-care resources on the basis of cost.

Project description:ImportanceHepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, and additional first-line treatments are needed. The programmed cell death protein 1 inhibitor tislelizumab demonstrated efficacy and a tolerable safety profile as second-line HCC treatment.ObjectiveTo investigate efficacy and safety of tislelizumab vs sorafenib tosylate for first-line treatment of unresectable HCC.Design, setting, and participantsThe open-label, global, multiregional phase 3 RATIONALE-301 randomized clinical trial enrolled systemic therapy-naive adults with histologically confirmed HCC, Barcelona Clinic Liver Cancer stage B or C disease, disease progression following (or patient was not amenable to) locoregional therapy, Eastern Cooperative Oncology Group performance status of 1 or less, and Child-Pugh class A, between December 27, 2017, and October 2, 2019. Data cutoff was July 11, 2022.InterventionPatients were randomized 1:1 to receive tislelizumab, 200 mg intravenously every 3 weeks, or sorafenib tosylate, 400 mg orally twice daily.Main outcomes and measuresThe primary end point was overall survival (OS); secondary end points included objective response rate, progression-free survival, duration of response, and safety.ResultsA total of 674 patients were included in the analysis (570 men [84.6%]; median age, 61 years [range, 23-86 years]). As of July 11, 2022, minimum study follow-up was 33 months. The primary end point of OS noninferiority of tislelizumab vs sorafenib was met in the intention-to-treat population (n = 674); median overall survival was 15.9 (95% CI, 13.2-19.7) months vs 14.1 (95% CI, 12.6-17.4) months, respectively (hazard ratio [HR], 0.85 [95.003% CI, 0.71-1.02]), and superiority of tislelizumab vs sorafenib was not met. The objective response rate was 14.3% (n = 49) for tislelizumab vs 5.4% (n = 18) for sorafenib, and median duration of response was 36.1 (95% CI, 16.8 to not evaluable) months vs 11.0 (95% CI, 6.2-14.7) months, respectively. Median progression-free survival was 2.1 (95% CI, 2.1-3.5) months vs 3.4 (95% CI, 2.2-4.1) months with tislelizumab vs sorafenib (HR, 1.11 [95% CI, 0.92-1.33]). The incidence of treatment-emergent adverse events (AEs) was 96.2% (325 of 338 patients) for tislelizumab and 100% (n = 324) for sorafenib. Grade 3 or greater treatment-related AEs were reported in 75 patients (22.2%) receiving tislelizumab and 173 (53.4%) receiving sorafenib. There was a lower incidence of treatment-related AEs leading to drug discontinuation (21 [6.2%] vs 33 [10.2%]) and drug modification (68 [20.1%] vs 187 [57.7%]) with tislelizumab vs sorafenib.Conclusions and relevanceIn RATIONALE-301, tislelizumab demonstrated OS benefit that was noninferior vs sorafenib, with a higher objective response rate and more durable responses, while median progression-free survival was longer with sorafenib. Tislelizumab demonstrated a favorable safety profile vs sorafenib.Trial registrationClinicalTrials.gov Identifier: NCT03412773.

Dataset Information

Clinical Impact of Vitamin K Dosing on Sorafenib Treatment for Hepatocellular Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets