Phase I Clinical Trial to Determine the Feasibility and Maximum Tolerated Dose of Panitumumab to Standard Gemcitabine-Based Chemoradiation in Locally Advanced Pancreatic Cancer
| Autor: | O. W. M. Meijer, Geertjan van Tienhoven, Henk M.W. Verheul, Elisa Giovannetti, Anna M.E. Bruynzeel, Annette A. van Zweeden, Maarten A J M Jacobs, Johanna W. Wilmink, Geert Kazemier, Hans J. van der Vliet, Martijn R. Meijerink |
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| Přispěvatelé: | Cancer Center Amsterdam, Oncology, Radiotherapy, Medical oncology, Radiology and nuclear medicine, Radiation Oncology, Medical oncology laboratory, Surgery, Gastroenterology and hepatology, CCA - Innovative therapy |
| Rok vydání: | 2015 |
| Předmět: |
Male
Oncology Radiation-Sensitizing Agents Cancer Research medicine.medical_specialty Maximum Tolerated Dose Combination therapy medicine.medical_treatment Phases of clinical research Antineoplastic Agents Deoxycytidine Disease-Free Survival Internal medicine medicine Humans Panitumumab Progression-free survival Aged Performance status business.industry Antibodies Monoclonal Chemoradiotherapy Middle Aged Combined Modality Therapy Gemcitabine ErbB Receptors Pancreatic Neoplasms Radiation therapy Female business medicine.drug |
| Zdroj: | van Zweeden, A A, van der Vliet, H J, Wilmink, J W, Meijerink, M R, Meijer, O W M, Bruynzeel, A M E, van Tienhoven, G, Giovannetti, E, Kazemier, G, Jacobs, M A J M & Verheul, H M W 2015, ' Phase I Clinical Trial to Determine the Feasibility and Maximum Tolerated Dose of Panitumumab to Standard Gemcitabine-Based Chemoradiation in Locally Advanced Pancreatic Cancer ', Clinical Cancer Research, vol. 21, no. 20, pp. 4569-4575 . https://doi.org/10.1158/1078-0432.CCR-14-3364 Clinical cancer research, 21(20), 4569-4575. American Association for Cancer Research Inc. Clinical Cancer Research, 21(20), 4569-4575. American Association for Cancer Research Inc. |
| ISSN: | 1078-0432 |
| DOI: | 10.1158/1078-0432.CCR-14-3364 |
| Popis: | Purpose: Epidermal growth factor receptor (EGFR) inhibitors may improve both the therapeutic efficacy of radiotherapy and the radiosensitizing activity of gemcitabine. Based on this rationale and the nonoverlapping toxicity profiles of gemcitabine and the monoclonal EGFR antibody panitumumab, we designed a phase I trial to investigate the maximum-tolerated dose (MTD), safety, and activity of panitumumab added to gemcitabine-based chemoradiotherapy (CRT) in patients with locally advanced pancreatic cancer (LAPC). Experimental Design: Patients with LAPC and WHO performance status 0 to 1 were treated with weekly panitumumab at four dose levels (1–2.5 mg/kg), combined with weekly gemcitabine 300 mg/m2 and radiotherapy (50.4 Gy in 28 fractions) for 6 weeks, followed by gemcitabine 1,000 mg/m2 weekly for 3 weeks every 4 weeks until disease progression or unacceptable toxicity. Each cohort was monitored during the combination therapy to establish dose limiting toxicity. Tumor evaluation was performed after CRT and during gemcitabine monotherapy. Results: Fourteen patients were enrolled; 14 were evaluable for toxicity and 13 for response. The MTD for panitumumab was 1.5 mg/kg. Three of the 6 patients, treated at MTD, experienced grade 3 adverse events during the combination therapy; neutropenia (n = 2; 33%), fatigue (n = 1; 17%), nausea (n = 1; 17%), and vomiting (n = 1; 17%). Partial response was achieved by 3 patients (23%), 1 in each dose cohort. Median progression free survival of the three cohorts together was 8.9 months. Conclusions: The addition of panitumumab to gemcitabine-based chemoradiotherapy in LAPC has manageable toxicity and potential clinical efficacy. Clin Cancer Res; 21(20); 4569–75. ©2015 AACR. |
| Databáze: | OpenAIRE |
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