A prospective,multicentre phase II trial of low-dose erlotinib in non-small cell lung cancer patients with EGFR mutations pretreated with chemotherapy: Thoracic Oncology Research Group 0911 |
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| Institution: | 1. Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan;2. Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan;3. Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan;4. Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen’s Hospital, Kanagawa, Japan;5. Division of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Kanagawa, Japan;6. Department of Respiratory Internal Medicine, St. Marianna University School of Medicine, Yokohama-City Seibu Hospital, Kanagawa, Japan;7. Department of Respiratory Medicine, Fujisawa City Hospital, Kanagawa, Japan;8. Department of Biostatistics, Yokohama City University Medical Center, Kanagawa, Japan;9. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan;10. Thoracic Oncology Research Group, Kanagawa, Japan;11. Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan;12. Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa, Japan;1. The University of Texas MD Anderson Cancer Center, Houston, TX, USA;2. UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA;3. DITEP, Gustave Roussy, Cancer Campus, Grand Paris, Villejuif, France;4. Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology VHIO, Barcelona, Spain;5. Oslo University Hospital, Oslo, Norway;6. Merck & Co., Inc., Kenilworth, NJ and North Wales, PA, USA;7. H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA;1. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea;2. Biomedical Knowledge Engineering Laboratory, Seoul National University, School of Dentistry, Seoul 110-749, Republic of Korea;3. Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea;4. Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Republic of Korea;5. Department of Pathology, Green Cross Laboratories, Yongin-si, Kyunggi-do 446-770, Republic of Korea;6. University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea;1. Department of Medical Oncology, Guys and St Thomas’ NHS Foundation, Great Maze Pond, London SE1 9RT, UK;2. Drug Development Unit, The Institute of Cancer Research, Downs Road, Sutton, Surrey SM2 5PT UK;3. The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK;4. Pharmacology and Translational Research, Boehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer Gasse 5-11, A1120 Vienna, Austria;5. Therapeutic Area Oncology, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Str 65, Biberach an der Riss 88397, Germany;6. Medical Department, Boehringer Ingelheim Ltd, Ellesfield Avenue, Bracknell RG12 8YS, UK;7. Biometrics and Data Management, Boehringer Ingelheim Ltd, Ellesfield Avenue, Bracknell RG12 8YS, UK;8. Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim GmbH & Co KG, Birkendorfer Str 65, Biberach an der Riss, 88397 Biberach an der Riss, Germany;9. King’s College London – Division of Cancer Studies, 3rd Floor, Bermondsey Wing, Guy’s Hospital, Great Maze Pond, London, SE1 9RT, UK;1. Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands;2. Biometrics Department, The Netherlands Cancer Institute, Amsterdam, The Netherlands;3. Pathology Department, The Netherlands Cancer Institute, Amsterdam, The Netherlands;4. Pulmonary Medicine, Amphia Ziekenhuis Breda, The Netherlands;5. Department of Radiation Oncology, Verbeeten Institute, Tilburg, The Netherlands;6. Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands;7. Pulmonary Medicine, Haga Ziekenhuis The Hague, The Netherlands;8. Pulmonary Medicine, Academic Medical Centre, Amsterdam, The Netherlands;9. Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands;1. Medical Oncology, Oncologisch Centrum, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium;2. Institut Catala d’Oncologia, Hospital Germans Trias I Pujol, Universitat Autònoma de Barcelona, Departament de Medicina, Badalona, Spain;3. Centre Hospitalier Chrétien, Liège, Belgium;4. ZNA Middelheim Hospital, Antwerp, Belgium;5. Clinique et Maternité Sainte-Elisabeth, Medical Oncology, Namur, Belgium;6. Grand Hospital de Charleroi, Oncologie-Hématologie, Grand Rue 3, Charleroi 6000, Belgium;7. Boehringer Ingelheim, Ltd., Bracknell, Berkshire, UK;8. Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA;9. Respiratory Oncology Unit, Department of Pulmonology, University Hospitals KU Leuven, Leuven, Belgium |
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| Abstract: | BackgroundLow-dose erlotinib may be as effective as gefitinib or erlotinib at full dose in non-small cell lung cancer (NSCLC) patients with activating mutations of the epidermal growth factor receptor (EGFR) gene.MethodsPatients with chemotherapy pretreated NSCLC harbouring EGFR mutations received erlotinib at 50 mg/d until disease progression or unacceptable toxicities. The dose was escalated to 150 mg/d in patients showing no response (i.e. without major tumour shrinkage according to Response Evaluation Criteria in Solid Tumours (RECIST)) to the initial dose during the first 4 weeks. The primary end-point was the objective response rate at the dose of 50 mg/d.ResultsThirty-four patients from seven institutes were enrolled. The study was closed early when no response was confirmed in 15 patients, excluding the possibility that the primary end-point would be met. The objective response and disease control rates at the dose of 50 mg/d as determined by an independent review committee were 54.5% and 84.8%, respectively. Four additional patients achieved partial response with increased 150 mg/d dose. Progression-free survival and median survival times during the entire period of the study were 9.5 and 28.5 months, respectively. Treatment-related toxicities were generally mild, the most common being skin disorders and diarrhoea. Only one case experienced grade 3 toxicity, which was transient increase of hepatic enzymes.ConclusionThe primary end-point was not met; low-dose erlotinib is not recommended for fit patients with NSCLC harbouring EGFR mutations. However, it may merit further evaluation for elderly or frail patients. |
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| Keywords: | Low-dose Erlotinib Non-small cell lung cancer |
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