Lack of pharmacokinetic drug-drug interaction between ramucirumab and irinotecan in patients with advanced solid tumors.
Cancer Chemother Pharmacol
; 78(4): 727-33, 2016 10.
Article
em En
| MEDLINE
| ID: mdl-27507037
ABSTRACT
PURPOSE:
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).METHODS:
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.RESULTS:
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.CONCLUSIONS:
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Camptotecina
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Anticorpos Monoclonais
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Neoplasias
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Antineoplásicos
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Antineoplásicos Fitogênicos
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos