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      Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

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          Abstract

          Osteosarcoma is the most frequent malignant primary bone tumor and a main cause of cancer-related death in children and adolescents. Although long-term survival in localized osteosarcoma has improved to about 60% during the 1960s and 1970s, long-term survival in both localized and metastatic osteosarcoma has stagnated in the past several decades. Thus, current conventional therapy consists of multi-agent chemotherapy, surgery and radiation, which is not fully adequate for osteosarcoma treatment. Innovative drugs and approaches are needed to further improve outcome in osteosarcoma patients. This review describes the current management of osteosarcoma as well as potential new therapies.

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          Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.

          Nicholas Vogelzang, James J Rusthoven, James T Symanowski … (2003)
          Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone. Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days. A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm (P =.020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed/cisplatin arm: 5.7 months versus 3.9 months (P =.001). Response rates were 41.3% in the pemetrexed/cisplatin arm versus 16.7% in the control arm (P <.0001). After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxicity, resulting in a significant reduction in toxicities in the pemetrexed/cisplatin arm. Treatment with pemetrexed plus cisplatin and vitamin supplementation resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma. Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time.
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            A renaissance for SRC.

            Timothy Yeatman (2004)
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              Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study.

              Tudor Ciuleanu, Thomas Brodowicz, Christoph Zielinski … (2009)
              Several studies have shown the efficacy, tolerability, and ease of administration of pemetrexed-an antifolate antineoplastic agent-in patients with advanced non-small-cell lung cancer. We assessed pemetrexed as maintenance therapy in patients with this disease. This randomised double-blind study was undertaken in 83 centres in 20 countries. 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy were randomly assigned (2:1 ratio) to receive pemetrexed (500 mg/m(2), day 1) plus best supportive care (n=441) or placebo plus best supportive care (n=222) in 21-day cycles until disease progression. Treatment was randomised with the Simon and Pocock minimisation method. Patients and investigators were masked to treatment. All patients received vitamin B(12), folic acid, and dexamethasone. The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00102804. All randomly assigned participants were analysed. Pemetrexed significantly improved progression-free survival (4.3 months [95% CI 4.1-4.7] vs 2.6 months [1.7-2.8]; hazard ratio [HR] 0.50, 95% CI 0.42-0.61, p<0.0001) and overall survival (13.4 months [11.9-15.9] vs 10.6 months [8.7-12.0]; HR 0.79, 0.65-0.95, p=0.012) compared with placebo. Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group (21 [5%] vs three [1%]). Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo (70 [16%] vs nine [4%]; p<0.0001), specifically fatigue (22 [5%] vs one [1%], p=0.001) and neutropenia (13 [3%] vs 0, p=0.006). No pemetrexed-related deaths occurred. Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy (227 [51%] vs 149 [67%]; p=0.0001). Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer. Eli Lilly.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancers (Basel)
                Journal ID (iso-abbrev): Cancers (Basel)
                Journal ID (publisher-id): cancers
                Title: Cancers
                Publisher: MDPI
                ISSN (Electronic): 2072-6694
                Publication date (Electronic): 24 May 2013
                Publication date Collection: June 2013
                Volume: 5
                Issue: 2
                Pages: 591-616
                Affiliations
                [1 ]INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes, France; E-Mails: mfheymann@ 123456chu-nantes.fr (M.-F.H.); verena.stresing@ 123456univ-nantes.fr (V.S.); francoise.redini@ 123456univ-nantes.fr (F.R.); dominique.heymann@ 123456univ-nantes.fr (D.H.)
                [2 ]Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes, France;
                [3 ]Equipe Labellisee Ligue 2012, Nantes, 44035 France
                [4 ]Nantes University Hospital, Nantes 44035, France
                [5 ]Department of Orthopaedic Surgery, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga 520-2192, Japan; E-Mail: kanchi@ 123456belle.shiga-med.ac.jp
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: andokercgv@ 123456gmail.com ; Tel.: +33-(0)-240-412-895; Fax: +33-(0)-272-641-132.
                Article
                Publisher ID: cancers-05-00591
                DOI: 10.3390/cancers5020591
                PMC ID: 3730336
                PubMed ID: 24216993
                SO-VID: 1797bd85-6ef3-4425-a3d9-3b8ae26d912f
                Copyright © © 2013 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 22 March 2013
                Date revision received : 28 April 2013
                Date accepted : 09 May 2013
                Categories
                Subject: Review

                Keywords: osteosarcoma,chemotherapy,surgery,radiotherapy,multidisciplinary treatment,emerging drugs
                Data availability:
                Keywords: osteosarcoma, chemotherapy, surgery, radiotherapy, multidisciplinary treatment, emerging drugs

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