Title

Lack of pharmacokinetic drug-drug interaction between ramucirumab and paclitaxel in a phase II study of patients with advanced malignant solid tumors.

Document Type

Article

Publication Date

8-1-2016

Publication Title

Cancer chemotherapy and pharmacology

Abstract

PURPOSE: The objective of this phase II study was to evaluate pharmacokinetic interaction potential between ramucirumab and paclitaxel in patients with advanced cancer.

METHODS: This study was designed to assess 2-way pharmacokinetic drug-drug interactions between ramucirumab and paclitaxel. Twenty-four patients participated in Part A, which consisted of a 2-week monotherapy period in which paclitaxel 80 mg/m(2) was administered on day 1, followed by a 4-week cycle of combination treatment with ramucirumab (8 mg/kg on days 1 and 15; paclitaxel on days 1, 8, and 15). Patients could continue to receive combination therapy with ramucirumab and paclitaxel. In 16 patients in Part B, ramucirumab monotherapy was administered on day 1 of a 3-week cycle. Patients could continue to receive ramucirumab monotherapy or combination therapy with paclitaxel.

RESULTS: Concomitant administration of ramucirumab had no effect on pharmacokinetics of paclitaxel, with ratios of geometric least squares (LS) means (with ramucirumab vs. alone) of 1.09 (90 % confidence interval [CI] 0.93, 1.29) for AUC(0-∞) and 0.97 (90 % CI 0.83, 1.13) for C max. In addition, similar ramucirumab pharmacokinetic characteristics were observed with or without paclitaxel administration. The ratios of geometric LS means of AUC(0-∞) and C max of ramucirumab (with paclitaxel vs. alone) were 1.00 (90 % CI 0.84, 1.19) for AUC(0-∞) and 1.07 (90 % CI 0.93, 1.24) for C max, respectively.

CONCLUSIONS: Concomitant paclitaxel administration is unlikely to affect the pharmacokinetics of ramucirumab, and vice versa. The incidence and severity of adverse events were consistent with the known safety profiles of paclitaxel and ramucirumab.

Medical Subject Headings

Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Drug Interactions; Female; Humans; Incidence; Least-Squares Analysis; Male; Middle Aged; Neoplasms; Paclitaxel; Young Adult

PubMed ID

27379498

Volume

78

Issue

2

First Page

433

Last Page

441

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