22nd Jan 2007 07:00
BTG PLC22 January 2007 BTG's Plevitrexed Shows Promising Efficacy and Tolerability in a Phase I/II study Data published at gastrointestinal cancers symposium London, UK, 22 January 2006: BTG plc (LSE: BGC), the medical innovationscompany, today announces the successful outcome of a Phase I/II study ofplevitrexed, a selective inhibitor of thymidylate synthase targeting gastric,pancreatic and ovarian cancer. The study, presented at the ASCO 2007Gastrointestinal Cancers Symposium1 in Orlando, Florida on 19 January, wasdesigned to investigate the efficacy, safety and tolerability of plevitrexed inpatients with advanced and/or metastatic gastric cancer. Of the 28 patients who were evaluable for response at the recommended dose levelof 130 mg/m2 taken into the Phase II part of the study, five patients had apartial response (17.9% response rate) and a further 15 patients (53.6%) hadstable disease giving an overall disease control rate of 71.4%. One patient onthe lower dose of 65 mg/m2 had a complete response and an additional fivepatients who received the higher dose of 165 mg/m2 had stable disease. The use of nutritional supplements improved the dosing consistency and allowedfor greater dose intensity. Only 30.6% of patients required dose interruptionsor modifications compared with 61.8% of patients in a previous plevitrexedstudy2. The maximum tolerated dose doubled to 130 mg/m2 and was given moreconsistently than in the previous study and with fewer missed doses, but noincrease in grade 3/4 neutropenia was observed. The overall efficacy of plevitrexed was in line with other single agenttherapy3,4 and with that seen in a previous study of plevitrexed5 (17% responserate), as well as with the recently reported two-drug combination treatment ofcisplatin and 5-FU in the V325 comparative study6 (25% response rate for thecisplatin/5FU arm). The Progression Free Survival of 120 days for plevitrexed inthe current study was similar to the Time To Progression of 111 days forcisplatin/5-FU in the V325 study, and median overall survival was also similar(239 days versus 258 days). The number of treatment cycles of cisplatin/5-FU wasthe same (4) but plevitrexed showed less toxicity, especially neutropenia(reduction in circulating white blood cells). In the V325 study the incidence ofgrade 3/4 neutropenia was 57% with 12% febrile neutropenia (with accompanyingfever), compared with an incidence of 39% grade 3/4 neutropenia with only 3%febrile neutropenia in the current plevitrexed study. Dr Anne Thomas, Senior Lecturer and Consultant in Medical Oncology at LeicesterRoyal Infirmary, a study investigator, commented: "With the promising singleagent activity and side-effect profile shown in this study, plevitrexedrepresents an alternative, simple treatment option for patients who would not beable to tolerate the toxicity of multi-drug combinations." Louise Makin, BTG's Chief Executive Office, added: "Based on the results of thisand previous studies, we believe that plevitrexed is potentially an importantnew treatment option for people with advanced or metastatic gastric cancer. Weare now seeking a partner to complete the clinical and commercial development ofplevitrexed in this and other cancer types." Study design The study was an open label, non-comparative multi-centre Phase I/II trial inchemotherapy naive patients with advanced and/or metastatic gastric cancer.Thirty patients were recruited to the Phase I part of the study designed toassess the safety and tolerability of different doses (65 mg/m2, 130 mg/m2 and165 mg/m2) of plevitrexed (days 1 and 8 of a 3-week cycle) with nutritionallevels of folic acid and vitamin B12 and to identify a dose for expansion intoPhase II. In the Phase II part of the study, an additional 25 patients wereadded to give a total of 36 at the recommended dose level of 130 mg/m2, of whom28 were evaluable for efficacy. Fifty-five patients who received at least onedose of plevitrexed were evaluable for toxicity. The most common clinical adverse events reported were nausea (16 patients),fatigue (15 patients), vomiting (11 patients) and diarrhoea (11 patients). Themost common grade 3/4 haematological events were neutropenia/leucopenia (21patients including 3 cases of febrile neutropenia), thrombocytopenia (4patients) and anaemia (12 patients). References 1 Thomas A et al. A Phase I/II Study of Plevitrexed in the Treatment of AdvancedGastric Cancer. American Society of Clinical Oncology 2007 GastrointestinalCancers Symposium (co-sponsors: AGA Institute, American Society for TherapeuticRadiology and Oncology, Society of Surgical Oncology, Inc.) 19-21 January 2007,Orlando, FL, USA, Abstract 79 2 Data on file 3 Ajani JA. Evolving Chemotherapy for Advanced Gastric Cancer. The Oncologist.2005; 10: 49-58 4 Starling N and Cunningham D. New Treatments for Advanced Gastric Cancer.Oncology 2006, Touch Briefings, London. 2006; pp25-30 5 Petruzelka L. Phase II multicentre trial of ZD9331 monotherapy as first-linetreatment for gastric cancer. Anti-Cancer Drugs. 2003; 14 (suppl 1): S7 - S12 6Van Cutsem E, Mioseyenko VM, et al. Phase III Study of Docetaxel and CisplatinPlus Fluorouracil As First-Line Therapy for Advanced Gastric Cancer: A Report ofthe V325 Study Group. Journal of Clinical Oncology. 2006; 24: 4991-4997 For further information contact: BTG Financial DynamicsAndy Burrows, Director of Investor Relations Ben Atwell/Anna Keeble+44 (0)20 7575 1741; mobile: +44 (0)7990 530605 +44 (0)20 7831 3113Christine Soden, Chief Financial Officer+44 (0)20 7575 1591 About BTG BTG in-licenses, develops and commercialises pharmaceuticals and other medicaltechnologies. With a substantial and growing revenue stream of royalties andmilestone payments from out-licensed products, BTG continues to strengthen itspipeline of preclinical and clinical development programmes. Active in thefields of oncology, diseases of ageing, neuroscience, drug repositioning andmedical devices, BTG works from its offices in London, Philadelphia and Osakawith a global partner network of healthcare companies and researchorganisations. For further information, visit: www.btgplc.com. This information is provided by RNS The company news service from the London Stock ExchangeRelated Shares:
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