Pharmacodynamic separation of gemcitabine and erlotinib in locally advanced or metastatic pancreatic cancer: therapeutic and biomarker results
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| 024 | 7 | 0 | |a 10.1007/s10147-014-0730-2 |2 doi |
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| 245 | 0 | 0 | |a Pharmacodynamic separation of gemcitabine and erlotinib in locally advanced or metastatic pancreatic cancer: therapeutic and biomarker results |h [Elektronische Daten] |c [Thomas Semrad, Afsaneh Barzi, Heinz-Josef Lenz, Irene Hutchins, Edward Kim, I-Yeh Gong, Michael Tanaka, Laurel Beckett, William Holland, Rebekah Burich, Leslie Snyder-Solis, Philip Mack, Primo Lara Jr.] |
| 520 | 3 | |a Purpose: Erlotinib marginally improves survival when administered continuously with gemcitabine to patients with advanced pancreatic cancer; however, preclinical data suggest that there is antagonism between chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors when these are delivered concurrently. We tested a pharmacodynamic separation approach for erlotinib plus gemcitabine and interrogated EGFR signaling intermediates as potential surrogates for the efficacy of this strategy. Methods: Patients with measurable, previously untreated locally advanced unresectable or metastatic pancreatic cancer were treated with gemcitabine 1000mg/m2 as an intravenous infusion over 30-min on days 1, 8, 15 and erlotinib 150mg/day on days 2-5, 9-12, 16-26 of each 28-day cycle. The primary endpoint was progression-free survival (PFS); secondary endpoints included RECIST objective response rate (ORR) and safety. The study was terminated after thirty patients due to funding considerations. Results: The median PFS was 2.07months (95% CI; 1.87-5.50months) and the ORR was 11%. No unexpected safety signals were seen: the most common grade 3 or higher adverse events were neutropenia (23%), lymphopenia (23%), and fatigue (13%). Patients with mutant plasma Kirsten rat sarcoma virus (KRAS) had significantly lower median PFS (1.8 vs. 4.6months, p=0.014) and overall survival (3.0 vs. 10.5months, p=0.003) than those without detected plasma KRAS mutations. Conclusions: Although pharmacodynamically separated erlotinib and gemcitabine were feasible and tolerable in patients with advanced pancreatic cancer, no signal for increased efficacy was seen in this molecularly unselected cohort. Detection of a KRAS mutation in circulating cell-free DNA was a strong predictor of survival. | |
| 540 | |a Japan Society of Clinical Oncology, 2014 | ||
| 690 | 7 | |a Gemcitabine |2 nationallicence | |
| 690 | 7 | |a Erlotinib |2 nationallicence | |
| 690 | 7 | |a Pancreatic cancer |2 nationallicence | |
| 690 | 7 | |a Pharmacodynamic separation |2 nationallicence | |
| 690 | 7 | |a KRAS mutation |2 nationallicence | |
| 700 | 1 | |a Semrad |D Thomas |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | |
| 700 | 1 | |a Barzi |D Afsaneh |u Medical Oncology, Keck School of Medicine, University of Southern California Norris Cancer Center, Los Angeles, CA, USA |4 aut | |
| 700 | 1 | |a Lenz |D Heinz-Josef |u Medical Oncology, Keck School of Medicine, University of Southern California Norris Cancer Center, Los Angeles, CA, USA |4 aut | |
| 700 | 1 | |a Hutchins |D Irene |u Department of Internal Medicine, University of California, Davis, Sacramento, CA, USA |4 aut | |
| 700 | 1 | |a Kim |D Edward |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | |
| 700 | 1 | |a Gong |D I-Yeh |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | |
| 700 | 1 | |a Tanaka |D Michael |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | |
| 700 | 1 | |a Beckett |D Laurel |u Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, Davis, CA, USA |4 aut | |
| 700 | 1 | |a Holland |D William |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | |
| 700 | 1 | |a Burich |D Rebekah |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | |
| 700 | 1 | |a Snyder-Solis |D Leslie |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | |
| 700 | 1 | |a Mack |D Philip |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | |
| 700 | 1 | |a Lara Jr. |D Primo |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | |
| 773 | 0 | |t International Journal of Clinical Oncology |d Springer Japan |g 20/3(2015-06-01), 518-524 |x 1341-9625 |q 20:3<518 |1 2015 |2 20 |o 10147 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s10147-014-0730-2 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s10147-014-0730-2 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Semrad |D Thomas |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Barzi |D Afsaneh |u Medical Oncology, Keck School of Medicine, University of Southern California Norris Cancer Center, Los Angeles, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Lenz |D Heinz-Josef |u Medical Oncology, Keck School of Medicine, University of Southern California Norris Cancer Center, Los Angeles, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Hutchins |D Irene |u Department of Internal Medicine, University of California, Davis, Sacramento, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kim |D Edward |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Gong |D I-Yeh |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Tanaka |D Michael |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Beckett |D Laurel |u Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, Davis, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Holland |D William |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Burich |D Rebekah |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Snyder-Solis |D Leslie |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Mack |D Philip |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Lara Jr |D Primo |u Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, 4501 X Street, Suite 3016, 95817, Sacramento, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t International Journal of Clinical Oncology |d Springer Japan |g 20/3(2015-06-01), 518-524 |x 1341-9625 |q 20:3<518 |1 2015 |2 20 |o 10147 | ||