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      Call for Papers: Beyond Biology: The Crucial Role of Sex and Gender in Oncology

      Submit here before May 31, 2024

      About Oncology Research and Treatment: 2.4 Impact Factor I 3.3 CiteScore I 0.495 Scimago Journal & Country Rank (SJR)

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      Long-Term Outcome of Combined Interferon-α and 5-Fluorouracil Treatment for Advanced Hepatocellular Carcinoma with Major Portal Vein Thrombosis

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          Abstract

          Background/Aim: We previously reported the beneficial effects of a combination therapy of interferon (IFN)-α/5-fluorouracil (FU) for advanced hepatocellular carcinoma (HCC) with tumor thrombi in the major portal branches. This report describes the results of longer follow-up and includes more than twice the number of patients relative to the previous report; it also evaluates the clinical predictor on the response to the combination therapy and long-term survival. Methods: The study subjects were 102 patients with advanced HCC and tumor thrombi in the major branches of the portal vein (Vp3 or 4). They were treated with at least 2 courses of IFN-α/5-FU. Results: No major treatment-related complications were noted. In the 102 patients, 40 (39.2%) showed objective response [11 (10.8%) showed complete response, 29 (28.4%) partial response], 8 (7.9%) showed no response and 54 (52.9%) showed progressive disease. Conclusion: IFN-α/5-FU combination therapy is a promising modality for advanced HCC with tumor thrombi in the major portal branches.

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          Molecular targeted therapies in hepatocellular carcinoma.

          Josep Llovet, Jordi Bruix (2008)
          Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with several genomic alterations. There is evidence of aberrant activation of several signaling cascades such as epidermal growth factor receptor (EGFR), Ras/extracellular signal-regulated kinase, phosphoinositol 3-kinase/mammalian target of rapamycin (mTOR), hepatocyte growth factor/mesenchymal-epithelial transition factor, Wnt, Hedgehog, and apoptotic signaling. Recently a multikinase inhibitor, sorafenib, has shown survival benefits in patients with advanced HCC. This advancement represents a breakthrough in the treatment of this complex disease and proves that molecular therapies can be effective in HCC. It is becoming apparent, however, that to overcome the complexity of genomic aberrations in HCC, combination therapies will be critical. Phase II studies have tested drugs blocking EGFR, vascular endothelial growth factor/platelet-derived growth factor receptor, and mTOR signaling. No relevant data has been produced so far in combination therapies. Future research is expected to identify new compounds to block important undruggable pathways, such as Wnt signaling, and to identify new oncogenes as targets for therapies through novel high-throughput technologies. Recent guidelines have established a new frame for the design of clinical trials in HCC. Randomized phase II trials with a time-to-progression endpoint are proposed as pivotal for capturing benefits from novel drugs. Survival remains the main endpoint to measure effectiveness in phase III studies. Patients assigned to the control arm should receive standard-of-care therapy, that is, chemoembolization for patients with intermediate-stage disease and sorafenib for patients with advanced-stage disease. Biomarkers and molecular imaging should be part of the trials, in order to optimize the enrichment of study populations and identify drug responders. Ultimately, a molecular classification of HCC based on genome-wide investigations and identification of patient subclasses according to drug responsiveness will lead to a more personalized medicine.
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            Transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a prospective comparative study.

            Jun Luo, Yao Zhang, Xi-Rong Guo … (2011)
            For patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT), the survival benefit of transarterial chemoembolization (TACE) compared with conservative treatment largely remains controversial. The objective of this study was to determine whether TACE confers a survival benefit to patients with HCC and PVTT, and to uncover prognostic factors. Between July 2007 and July 2009, a prospective two-arm nonrandomized study was performed on consecutive patients with unresectable HCC with PVTT. In one arm, patients were treated by TACE using an emulsion of lipiodol and anticancer agents ± gelatin sponge embolization. In another arm, patients received conservative treatment. A total of 164 patients were recruited for the study (TACE group, n = 84; conservative treatment group, n = 80). Patients in the TACE group received a mean of 1.9 (range, 1-5) TACE sessions. The overall median survival for all patients was 5.2 months, and the 12- and 24-month overall survival rates were 18.3% and 5.6%, respectively. The 12- and 24-month overall survival rates for the TACE and conservative groups were 30.9%, 9.2%, and 3.8%, 0%, respectively. The TACE group had significantly better survivals than the conservative group (P < 0.001). On subgroup analysis of segmental and major PVTT, the TACE group also had significantly better survivals (P = 0.002, P = 0.002). The treatment type, PVTT extent, tumor size, and serum bilirubin were independent prognostic factors of survival on multivariate analysis. TACE was safe and feasible in selected HCC patients with PVTT and it had survival benefit over conservative treatment.
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              Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study.

              Aram Hezel, Pankaj Bhargava, Marek Ancukiewicz … (2009)
              To assess the safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma (HCC) and explore biomarkers for sunitinib response. We conducted a multidisciplinary phase II study of sunitinib, an antivascular endothelial growth factor receptor tyrosine kinase inhibitor, in advanced HCC. Patients received sunitinib 37.5 mg/d for 4 weeks followed by 2 weeks of rest per cycle. The primary end point was progression-free survival (PFS). We used functional magnetic resonance imaging to evaluate vascular changes in HCC after sunitinib treatment. Circulating molecular and cellular biomarkers were evaluated before and at six time points after sunitinib treatment. Thirty-four patients were enrolled. The objective response rate was 2.9%, and 50% of patients had stable disease. Median PFS was 3.9 months (95% CI, 2.6 to 6.9 months), and overall survival was 9.8 months (95% CI, 7.4 months to not available). Grade 3 or 4 toxicities included leukopenia/neutropenia, thrombocytopenia, elevation of aminotransferases, and fatigue. Sunitinib rapidly decreased vessel leakiness, and this effect was more pronounced in patients with delayed progression. When evaluated early (at baseline and day 14) as well as over three cycles of treatment, higher levels of inflammatory molecules (eg, interleukin-6, stromal-derived factor 1alpha, soluble c-KIT) and circulating progenitor cells were associated with a poor outcome. Sunitinib shows evidence of modest antitumor activity in advanced HCC with manageable adverse effects. Rapid changes in tumor vascular permeability and circulating inflammatory biomarkers are potential determinants of response and resistance to sunitinib in HCC. Our study suggests that control of inflammation might be critical for improving treatment outcome in advanced HCC.
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                Author and article information

                Journal
                Journal ID (publisher-id): OCL
                Journal ID (nlm-ta): Oncology
                Journal ID (doi): 10.1159/issn.0030-2414
                Title: Oncology
                Publisher: S. Karger AG
                ISSN (Print): 0030-2414
                ISSN (Electronic): 1423-0232
                Publication date Subscription-year: 2011
                Publication date (Print): June 2011
                Publication date (Electronic): 09 June 2011
                Volume: 80
                Issue: 1-2
                Pages: 63-69
                Affiliations
                Departments of aSurgery, bRadiology and cHealth Science, Graduate School of Medicine, Osaka University, Suita, Japan
                Author notes
                *Hiroaki Nagano, MD, PhD, Department of Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka E-2, Suita 565-0871 (Japan), Tel. +81 6 6879 3251, E-Mail hnagano@gesurg.med.osaka-u.ac.jp
                Article
                Publisher ID: 328281 Other ID: Oncology 2011;80:63–69
                DOI: 10.1159/000328281
                PubMed ID: 21659784
                SO-VID: e4570ae0-1ee0-4d49-b864-c8995cc9cf0d
                Copyright © © 2011 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 06 September 2010
                Date accepted : 07 February 2011
                Page count
                Figures: 2, Tables: 2, Pages: 7
                Categories
                Subject: Clinical Study

                ScienceOpen disciplines: Oncology & Radiotherapy,Pathology,Surgery,Obstetrics & Gynecology,Pharmacology & Pharmaceutical medicine,Hematology
                Keywords: Portal vein tumor thrombosis,Interferon,Hepatocellular carcinoma,Arterial infusion chemotherapy
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy, Pathology, Surgery, Obstetrics & Gynecology, Pharmacology & Pharmaceutical medicine, Hematology
                Keywords: Portal vein tumor thrombosis, Interferon, Hepatocellular carcinoma, Arterial infusion chemotherapy

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