Lack of pharmacokinetic drug–drug interaction between ramucirumab and irinotecan in patients with advanced solid tumors
| Autor: | Fadi Braiteh, Ling Gao, Christopher John Asakiewicz, James J. Lee, Yong Lin, F. Nasroulah, Ding Wang, Archana Chaudhary, Dale R. Shepard, Crystal S. Denlinger, Patricia LoRusso |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research medicine.medical_specialty Leucovorin Phases of clinical research Antineoplastic Agents SN-38 Neutropenia Pharmacology Antibodies Monoclonal Humanized Irinotecan Toxicology Gastroenterology Ramucirumab 03 medical and health sciences Folinic acid chemistry.chemical_compound 0302 clinical medicine Asian People Pharmacokinetics Neoplasms Internal medicine medicine Humans Drug Interactions Pharmacology (medical) Aged Antibiotics Antineoplastic business.industry Antibodies Monoclonal Middle Aged medicine.disease Antineoplastic Agents Phytogenic 030104 developmental biology Oncology chemistry Area Under Curve 030220 oncology & carcinogenesis FOLFIRI Camptothecin Female Fluorouracil business medicine.drug |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 78:727-733 |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | The objective of this phase II study was to evaluate the potential of pharmacokinetic (PK) drug–drug interactions between ramucirumab and irinotecan or its metabolite, SN-38, when administered with folinic acid and 5-fluorouracil (FOLFIRI). Patients received intravenous infusions of FOLFIRI and ramucirumab 8 mg/kg on Day 1 of a 2-week cycle. FOLFIRI was administered alone in Cycle 1; ramucirumab followed by FOLFIRI was administered in all subsequent cycles. Blood was collected at regular intervals after infusions in Cycles 1 and 2 to determine irinotecan, SN-38, and ramucirumab concentrations. PK parameters were derived by noncompartmental analysis. Twenty-nine patients received treatment. The dose-normalized area under the concentration versus time curve from zero to infinity [AUC(0–∞)] and the maximum observed concentration (C max) of irinotecan and SN-38 were comparable between Cycle 1 (FOLFIRI alone) and Cycle 2 (ramucirumab + FOLFIRI). The ratios of geometric least squares (LS) means for irinotecan were 0.93 (90 % CI 0.83–1.05) for AUC(0–∞) and 1.04 (90 % CI 0.97–1.12) for C max. The ratios of geometric LS means for SN-38 were 0.95 (90 % CI 0.88–1.04) for AUC(0–∞) and 0.97 (90 % CI 0.85–1.12) for C max. The most common treatment-emergent adverse events, regardless of grade, were fatigue (19 patients, 65.5 %), diarrhea, (16 patients, 55.2 %), and neutropenia (15 patients, 51.7 %). Grade ≥3 neutropenia was reported in 7 (24.1 %) patients. There was no PK drug–drug interaction between ramucirumab and irinotecan or its metabolite, SN-38. Ramucirumab with FOLFIRI was well tolerated in this study, with no new safety concerns. |
| Databáze: | OpenAIRE |
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