A phase II study of erlotinib in gemcitabine refractory advanced pancreatic cancer |
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| Institution: | 1. British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada;2. Tom Baker Cancer Centre, Calgary, AB, Canada;3. University Health Network-Princess Margaret Cancer Centre, Toronto, ON, Canada;4. Cross Cancer Institute, Edmonton, AB, Canada;1. Department of Nuclear Medicine, Saint-Louis Hospital, Paris, France;2. B2T, Doctoral School, IUH, University of Paris VII, France;3. Department of Nuclear Medicine, CHU Bordeaux, University of Bordeaux, France;4. Breast Diseases Unit and Department of Medical Oncology, Saint-Louis Hospital, Paris, France;5. Department of Biostatistics, Institut Curie, Paris, France;6. Department of Pathology, Saint-Louis Hospital, Paris, France;7. Department of Biochemistry, Saint-Louis Hospital, Paris, France;8. Centre for Therapeutic Innovation, Saint Louis Hospital, Paris, France;9. INSERM, UMR 1101 LaTIM, Brest, France;1. Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Japan;2. Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Japan;3. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Japan;4. Department of Surgery, Toho University School of Medicine, Japan;1. Department of Physics and Astronomy, University of Calgary, Calgary, AB, Canada;2. Department of Medical Physics, Tom Baker Cancer Centre, Calgary, AB, Canada;3. Department of Oncology, University of Calgary, Calgary, AB, Canada;1. Department of Gastroenterology, Hospital Clínic Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain;2. Pathology Department, Centre de Diagnòstic Biomèdic, Hospital Clinic, University of Barcelona, and Banc de Tumors-Biobanc Clinic-IDIBAPS, Spain;3. Medical Oncology Department, Hospital Miguel Servet, Zaragoza, Spain;4. Medical Oncology Department, Hospital Clínico de Zaragoza, Spain;5. Medical Oncology Department, Hospital Clínic Barcelona, Spain;6. Pathology Department, Hospital Miguel Servet, Zaragoza, Spain;7. Pathology Department, Hospital Clinico Zaragoza, Spain;8. Department of Epidemiology, Harvard Medical School of Public Health, Boston, USA;9. Bioinformatics Unit, CIBERehd, Barcelona, Catalonia, Spain;10. Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain;1. Department of Pathology, Ludwig-Maximilians-University of Munich, Germany;2. Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany;3. German Cancer Consortium (DKTK), Heidelberg, Germany;4. German Cancer Research Center (DKFZ), Heidelberg, Germany;5. Clovis Oncology Inc., San Francisco, CA, USA;6. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Germany;7. Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany |
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| Abstract: | BackgroundErlotinib induced skin toxicity has been associated with clinical benefit in several tumour types. This phase II study evaluated the efficacy of erlotinib, dose escalated to rash, in patients with advanced pancreatic cancer previously treated with gemcitabine.MethodsErlotinib was given at an initial dose of 150 mg/day, and the dose was escalated by 50 mg every 2 weeks (to a maximum of 300 mg/day) until >grade 1 rash or other dose limiting toxicities occurred. Erlotinib pharmacokinetics were performed, and baseline tumour tissue was collected for mutational analysis and epidermal growth factor receptor (EGFR) expression. The primary end-point was the disease control rate (objective response and stable disease >8 weeks).ResultsFifty-one patients were accrued, and 49 received treatment. Dose-escalation to 200–300 mg of erlotinib was possible in 9/49 (18%) patients. The most common ?grade 3 adverse events included fatigue (6%), rash (4%) and diarrhoea (4%). Thirty-seven patients were evaluable for response, and the best response was stable disease in 12 patients (32% (95% confidence interval (CI) 17–47%)). Disease control was observed in nine patients (24% (95% CI: 10–38%)). Median survival was 3.8 months, and 6 month overall survival rate was 32% (95% CI 19–47%). Mutational analysis and EGFR expression were performed on 29 patients, with 93% having KRAS mutations, none having EGFR mutations, and 86% expressing EGFR. Neither KRAS mutational status nor EGFR expression was associated with survival.ConclusionsErlotinib dose escalated to rash was well tolerated but not associated with significant efficacy in non-selected patients with advanced pancreatic cancer. |
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| Keywords: | Pancreatic cancer Erlotinib Phase II |
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