Dataset Information

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

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

SUBMITTER: Chow LQ

PROVIDER: S-EPMC4965482 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Chow Laura Q M LQ Smith David C DC Tan Antoinette R AR Denlinger Crystal S CS Wang Ding D Shepard Dale R DR Chaudhary Archana A Lin Yong Y Gao Ling L

Cancer chemotherapy and pharmacology 20160705 2

<h4>Purpose</h4>The objective of this phase II study was to evaluate pharmacokinetic interaction potential between ramucirumab and paclitaxel in patients with advanced cancer.<h4>Methods</h4>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 tr ...[more]

PMID: 27379498

Similar Datasets

Project description:Background Nanoparticle albumin-bound paclitaxel (nab-PTX) has shown non-inferiority to paclitaxel (PTX) as second-line therapy for advanced gastric cancer (AGC) with fewer infusion-related reactions. The efficacy and safety of nab-PTX plus ramucirumab (RAM) was reported in a phase II trial; however, there is no randomized trial comparing this regimen with PTX plus RAM in patients with AGC. This retrospective study aimed to investigate the efficacy and safety of nab-PTX plus RAM versus PTX plus RAM in patients with AGC. Methods This study included patients with AGC who received nab-PTX plus RAM from September 2017 to January 2019 or PTX plus RAM from June 2015 to August 2017 as second-line chemotherapy in our hospital. Results A total of 113 and 138 patients who received nab-PTX plus RAM and PTX plus RAM, respectively, were analyzed. Median progression-free survival (PFS) was 3.9?months (95% confidence interval [CI]: 3.4–4.3) in the nab-PTX plus RAM group and 3.9?months (95% CI: 3.1–4.7) in the PTX plus RAM group (hazard ratio [HR]: 1.08; 95% CI: 0.83–1.40; P?=?0.573). Median overall survival (OS) was 10.9?months (95% CI: 9.3–12.7) in the nab-PTX plus RAM group and 10.3?months (95% CI: 8.5–12.0) in the PTX plus RAM group (hazard ratio: 0.82; 95% CI: 0.61–1.10; P?=?0.188). In patients with moderate/massive ascites, favorable outcomes for progression-free survival were observed in the nab-PTX plus RAM group compared with the PTX plus RAM group. Although anemia and fatigue (any grade) were more frequent in the nab-PTX plus RAM group, discontinuation of study treatment was not increased in the nab-PTX plus RAM group. There was no occurrence of hypersensitivity reaction in the nab-PTX plus RAM group, while two patients (1.4%) experienced grade 3 hypersensitivity reactions in the PTX plus RAM group. Conclusions The combination of nab-PTX plus RAM showed a similar efficacy and safety profile to PTX plus RAM as second-line treatment for patients with AGC. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-020-07614-6.

Project description:BackgroundRamucirumab is a widely used cancer drug having gained six regulatory approvals in various advanced solid tumors. Thus, assessing the risk-benefit profile of such a commonly used drug across multiple tumor types is necessary to inform clinical and reimbursement decisions. To objectively assess the risks and benefits of ramucirumab in patients with advanced solid tumors, we performed a systematic review and meta-analysis of published randomized controlled trials (RCTs).MethodsA systematic search of PubMed, the Cochrane Library, Google Scholar and conference abstracts for all RCTs of ramucirumab in patients with advanced solid cancer was conducted according to the PRISMA guidelines. Data on treatment-related serious adverse events (SAEs), fatal adverse events (FAEs), primary endpoint, gains in median overall survival (OS), progression-free survival (PFS) with their hazard ratios (HR) and 95% confidence intervals (CIs) and quality of life (QOL) were extracted from each RCT. Summary relative risks (RR) with 95% CI for SAEs and FAEs were calculated by pooling data across the RCTs using random-effects model. Treatment benefit was evaluated descriptively in terms of median and HR with 95% CI of OS and PFS gains as well as improvements in QOL. ESMO-Magnitude of Clinical Benefit Scale (MCBS), a validated tool, was used to objectively quantify clinical benefit of ramucirumab in approved settings.FindingsTen RCTs met our inclusion criteria. Compared with the control arm, the use of ramucirumab was associated with a significantly increased risk of developing SAE (RR 1.13, 95% CI 1.05-1.21, incidence 37.5% v 33.5%). The increase in risk of FAE (RR 1.41, 95% CI 0.96-2.07, incidence 1.8% v 1.3%) was not statistically significant. Using the ESMO MCBS tool, clinical benefit with ramucirumab was not substantial in any indication, five of six approvals scoring a "negligible benefit" score of 1 or 2. QOL was either not reported (30%) or not improved (70%) in these RCTs.InterpretationIn this meta-analysis of RCTs, use of ramucirumab in patients with advanced cancer was associated with increased risk of treatment related serious and possibly fatal adverse events but the magnitude of clinical benefit from ramucirumab was mostly negligible with no trial reporting an improvement in QOL. These relative risks and benefits should be considered in clinical and regulatory decision making.FundingNone.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets