A phase I study of intravenous aflibercept with FOLFIRI in Japanese patients with previously treated metastatic colorectal cancer
| Autor: | Tadahiro Fujino, Atsushi Ohtsu, Nozomu Machida, Yusuke Onozawa, Kentaro Yamazaki, Masako Asayama, Narikazu Boku, Toshihiko Doi, Kensei Yamaguchi, Takayuki Yoshino |
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| Jazyk: | angličtina |
| Předmět: |
Male
Vascular Endothelial Growth Factor A medicine.medical_specialty Combination therapy Recombinant Fusion Proteins Leucovorin Antineoplastic Agents Pharmacology Neutropenia Gastroenterology FOLFIRI Asian People Internal medicine Phase I Studies Antineoplastic Combined Chemotherapy Protocols medicine Humans Pharmacology (medical) Neoplasm Metastasis Adverse effect Aflibercept Aged Leukopenia business.industry Metastatic colorectal cancer Vascular endothelial growth factor (VEGF) Middle Aged medicine.disease Irinotecan Receptors Vascular Endothelial Growth Factor Oncology Fluorouracil Phase I study Aflibercept (VEGF trap) Administration Intravenous Camptothecin Female medicine.symptom business Colorectal Neoplasms medicine.drug |
| Zdroj: | Investigational New Drugs |
| ISSN: | 0167-6997 0092-1661 |
| DOI: | 10.1007/s10637-012-9895-6 |
| Popis: | Summary Aflibercept, a recombinant fusion protein, is a potent inhibitor of vascular endothelial growth factor (VEGF)-A, VEGF-B, and the placental growth factor (PlGF). The present study was an open-label, sequential-cohort, dose-escalation trial of intravenous aflibercept administered every 2 weeks in combination with 5-fluorouracil, levofolinate, and irinotecan (FOLFIRI) in patients with previously treated metastatic colorectal cancer (mCRC). We aimed to assess the safety, dose-limiting toxicities (DLTs), pharmacokinetics, and preliminary efficacy of the combination therapy to determine the recommended phase II dose (RPTD) for Japanese patients. Two doses of aflibercept (2.0 and 4.0 mg/kg) were set, and DLTs were evaluated in the first 2 cycles. The subjects comprised 16 patients (n = 3 and 13 for 2.0 and 4.0 mg/kg aflibercept, respectively) who received a total of 149 cycles of aflibercept with FOLFIRI. No DLTs were observed at both doses. The frequent adverse events encountered were leukopenia, neutropenia, anemia, diarrhea, fatigue, decreased appetite, stomatitis, dysphonia, nausea, and epistaxis. The most common grade 3/4 adverse events were neutropenia for both doses and hypertension for the 4.0 mg/kg dose. Free aflibercept exposure increased with the dose, whereas exposure to VEGF-bound aflibercept remained similar at both doses. The response rate and progression-free survival at 4.0 mg/kg was 8.3 % and 7.59 months, respectively. In conclusion, the combination of aflibercept and FOLFIRI was well tolerated at both doses. The RPTD of aflibercept in combination with FOLFIRI for Japanese patients with mCRC was determined to be 4.0 mg/kg every 2 weeks. ClinicalTrials.gov identifier: NCT00921661 |
| Databáze: | OpenAIRE |
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