The combination of a chemotherapy doublet (gemcitabine and capecitabine) with a biological doublet (bevacizumab and erlotinib) in patients with advanced pancreatic adenocarcinoma. The results of a phase I/II study |
| |
| Affiliation: | 1. Department of Medicine, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, United Kingdom;2. Department of Diagnostic Imaging, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, United Kingdom;3. Computing and Statistics, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, United Kingdom;1. Queen Elizabeth Central Hospital, Blantyre, Malawi;2. University of Malawi, Zomba, Malawi;3. Royal Marsden Hospital, London, UK;4. College of Medicine, Blantye, Malawi;5. VU University Medical Centre, Amsterdam, The Netherlands;6. The Great Northern Hospital, Newcastle, UK;7. The Malawi Liverpool Wellcome Trust Research Laboratories, College of Medicine, Blantyre, Malawi;1. Gynecologic Oncology, University Hospitals Leuven, Herestraat, 49, 3000 Leuven, Belgium;2. Division of Oncology, KULeuven, Herestraat, 49, 3000 Leuven, Belgium;3. Department of Obstetrics and Gynecology, 2nd Medical Faculty, Charles University, Ovocný trh, 5, 11636 Prague, Czech Republic;4. Department of Gynecologic Oncology, Center Gynecologic Oncology, Plesmanlaan, 121, 1066 CX Amsterdam, The Netherlands;5. Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, Geert Grooteplein-Zuid, 10, 6525 GA Nijmegen, The Netherlands;6. Division of Obstetrics and Gynecology, San Gerardo Hospital, University of Milan-Bicocca, Via Pergolesi, 33, 20900 Monza, Italy;7. Department of Radiotherapy and Clinical Oncology, Vejle Hospital, Brummersvej, 1, DK-7100 Vejle, Denmark;8. University Hospital of Krakow (Jagiellonian University), Department of Gynecology and Oncology, Gołębia, 24, Kraków, Poland;9. Physics Department in Radiation-Oncology, University Hospitals Leuven, Herestraat, 49, 3000 Leuven, Belgium;10. Neurosurgery, University Hospitals Leuven, Herestraat, 49, 3000 Leuven, Belgium;11. General Medical Oncology, University Hospitals Leuven, Herestraat, 49, 3000 Leuven, Belgium;12. Radiation-Oncology, University Hospitals Leuven, Herestraat, 49, 3000 Leuven, Belgium;1. Department of Surgery, College of Medicine, University of Ulsan and Asan Medical Center, Republic of Korea;2. Department of Oncology, College of Medicine, University of Ulsan and Asan Medical Center, Republic of Korea;1. Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark;2. Unit of Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark;3. Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark;4. Gynaecologic Clinic, Juliane Marie Center, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark;1. Institute of Urologic Oncology, Department of Urology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA;2. Department of Urology, University Medicine Greifswald, Germany;3. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles,CA, USA;4. Department of Pathology, Dana Farber Cancer Institute, Harvard School of Medicine, Boston, MA, USA;1. Department of Oncology, Odense University Hospital, Odense, Denmark;2. Department of Oncology, Rigshospitalet, Copenhagen, Denmark;3. Danish Breast Cancer Cooperative Group, Copenhagen, Denmark;4. Dako Denmark A/S, Glostrup, Denmark;5. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark;6. Department of Oncology, Herlev University Hospital, Herlev, Denmark;7. Department of Pathology, Slagelse Hospital, Slagelse, Denmark |
| |
| Abstract: | BackgroundPreclinical data support the combined inhibition of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways in the treatment of pancreatic cancer. Following a dose finding phase I study the efficacy and toxicity of a four-drug regimen utilising the cytotoxic doublet of gemcitabine and capecitabine (GemCap), with the biological doublet of erlotinib and bevacizumab were further assessed in patients with advanced pancreatic cancer.Patients and methodsIn a phase II expansion cohort, patients with chemonaive locally advanced or metastatic pancreatic cancer received gemcitabine (1000 mg/m2 D1, 8, 15), capecitabine (1400 mg/m2 D1–21), erlotinib (100 mg daily) and bevacizumab (5 mg/kg D1, 15) every 28 days. The primary endpoint was radiological response rate by response evaluation criteria in solid tumours (RECIST). Computed tomography (CT) assessment was performed every 8 weeks. Consolidation radiotherapy was considered in locally advanced patients following six cycles of treatment.ResultsIn total 44 patients (phases I & II) were recruited. The median cycles delivered were 6 (range 1–16). Confirmed radiological responses were seen in 23% (95% confidence interval (CI): 11–38%) of patients. The median progression-free and overall survival for the entire cohort was 8.4 and 12.6 months, respectively. In patients with metastatic disease the median overall survival was 10.1 months. Common grade 3/4 toxicities were; neutropenia 52%, lethargy 32%, diarrhoea 18% and hand-foot syndrome 18%.ConclusionThe combination of gemcitabine, capecitabine, erlotinib and bevacizumab was feasible with a manageable toxicity profile and demonstrated encouraging efficacy data in a good performance status population. |
| |
| Keywords: | Anti-angiogenic therapy Chemotherapy Combination chemotherapy Epidermal growth factor receptor (EGFR) inhibition Molecularly targeted therapy Pancreatic cancer |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
