Pharmacokinetics and metabolism of docetaxel administered as a 1-h intravenous infusion

Rosing, Hilde; Lustig, Vera; Warmerdam, L. J. C. van; Huizing, Manon; Huinink, W.W. ten Bokkel; Schellens, Jan H.M.; Rodenhuis, S.; Bult, A.; Beijnen, Jos H.

doi:10.1007/s002800050032

Cited by 64 publications

(41 citation statements)

References 12 publications

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“…Bortezomib was eliminated from plasma with similar terminal half-lives across dose levels, with mean values of 15 -18 h following the first dose in patients with measurable plasma concentrations at 24 h post-dose (Table 5). Pharmacokinetic characteristics of bortezomib/docetaxel were comparable with single-agent data (Millennium Pharmaceuticals Inc.; Rosing et al, 2000).…”

Section: Pharmacokineticssupporting

confidence: 58%

Bortezomib/docetaxel combination therapy in patients with anthracycline-pretreated advanced/metastatic breast cancer: a phase I/II dose-escalation study

et al. 2008

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The aim of this study was to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of bortezomib plus docetaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer. Forty-eight patients received up to eight 21-day cycles of docetaxel (60 -100 mg m À2 on day 1) plus bortezomib (1.0 -1.5 mg m À2 on days 1, 4, 8, and 11). Pharmacodynamic and pharmacokinetic analyses were performed in a subset of patients. Five patients experienced DLTs: grade 3 bone pain (n ¼ 1) and febrile neutropenia (n ¼ 4). The MTD was bortezomib 1.5 mg m À2 plus docetaxel 75 mg m À2 . All 48 patients were assessable for safety and efficacy. The most common adverse events were diarrhoea, nausea, alopecia, asthenia, and vomiting. The most common grade 3/4 toxicities were neutropenia (44%), and febrile neutropenia and diarrhoea (each 19%). Overall patient response rate was 29%. Median time to progression was 5.4 months. In patients with confirmed response, median time to response was 1.3 months and median duration of response was 3.2 months. At the MTD, response rate was 38%. Pharmacokinetic characteristics of bortezomib/ docetaxel were comparable with single-agent data. Addition of docetaxel appeared not to affect bortezomib inhibition of 20S proteasome activity. Mean alpha-1 acid glycoprotein concentrations increased from baseline at nearly all time points across different bortezomib dose levels. Bortezomib plus docetaxel is an active combination for anthracycline-pretreated advanced/metastatic breast cancer. The safety profile is manageable and consistent with the side effects of the individual agents.

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Section: Pharmacokineticssupporting

confidence: 58%

Bortezomib/docetaxel combination therapy in patients with anthracycline-pretreated advanced/metastatic breast cancer: a phase I/II dose-escalation study

et al. 2008

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“…Mean clearance values (using the Bayesian estimation for individual clearance based on all evaluated courses) did not differ between the 2 dosing strategies. Moreover, interpatient variability (CV) of the clearance was within previously reported ranges for both dosing groups (7,25). Respective values for the BSA-based and PK-guided group were 39.1 AE 9.7 L/h (25%) and 39.7 and on a logarithmic scale (i.e., SD of ln AUC) from 0.23 to 0.14.…”

Section: Pk Analysismentioning

confidence: 65%

Therapeutic Drug Monitoring for the Individualization of Docetaxel Dosing: A Randomized Pharmacokinetic Study

Engels

Loos

Bol

et al. 2011

Clinical Cancer Research

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Purpose: Docetaxel pharmacokinetic (PK) parameters, notably clearance and exposure (AUC), are characterized by large interindividual variability. The purpose of this study was to evaluate the effect of PKguided [area under the plasma concentration versus time curve (AUC) targeted], individualized docetaxel dosing on interindividual variability in exposure.Experimental Design: A limited sampling strategy in combination with a validated population PK model, Bayesian analysis, and a predefined target AUC was used. Fifteen patients were treated for at least 2 courses with body surface area-based docetaxel and 15 with at least 1 course of PK-guided docetaxel dosing.Results: Interindividual variability (SD of ln AUC) was decreased by 35% (N ¼ 15) after 1 PK-guided course; when all courses were evaluated, variability was decreased by 39% (P ¼ 0.055). PK-guided dosing also decreased the interindividual variability of percentage decrease in white blood cell and absolute neutrophil counts by approximately 50%.Conclusions: Further research is required to determine whether the decrease in PK variability can contribute to a reduction in interindividual variability in efficacy and toxicity. Clin Cancer Res; 17(2); 353-62.Ó2011 AACR.

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“…In a pooled analysis, it had a terminal half-life of 10.4 hours, clearance of 35 l/hour-m 2 , and apparent distribution volume (V d ) at steady state of 67.3 l/m 2 . Both the V d and clearance are high, indicating extensive drug distribution and/or protein binding [11].…”

Section: Docetaxel and Sarcomasmentioning

confidence: 99%

Gemcitabine and Docetaxel in Metastatic Sarcoma: Past, Present, and Future

Maki

2007

The Oncologist

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Objective. In the era of oral molecular kinase inhibitors, cytotoxic chemotherapy agents are somewhat overlooked, but remain the backbone of treatment for most cancers. Patients with non-gastrointestinal stromal tumor sarcomas, such as leiomyosarcoma, liposarcoma, and undifferentiated high-grade pleomorphic sarcoma (formerly called malignant fibrous histiocytoma), have received doxorubicin and ifosfamide as the backbone of their treatment for over 15 years or more. The goal of this article is to review the data that have led to the use of gemcitabine and docetaxel as a useful combination for patients with metastatic sarcomas, and to comment on possible synergy of the combination.Methods and results. The literature regarding the use of gemcitabine, docetaxel, or both, is reviewed, with emphasis on patients with metastatic sarcoma.Results. Activity of gemcitabine and docetaxel is observed in leiomyosarcoma and undifferentiated highgrade pleomorphic sarcoma. There is apparent schedule dependence of the combination in other cancers; it is unclear if schedule matters in patients with sarcomas. The dose and schedule of gemcitabine and docetaxel examined in phase II studies are probably too high for routine practice.Conclusions. The combination of gemcitabine and docetaxel is an effective option for patients with metastatic sarcoma, increasing the armamentarium for the practicing oncologist in treating this heterogeneous group of diseases. Given the low response rate to docetaxel as a single agent, it is likely that there is true clinical synergy of the combination. The Oncologist 2007;12: 999 -1006 Disclosure of potential conflicts of interest is found at the end of this article.

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Pharmacokinetics and metabolism of docetaxel administered as a 1-h intravenous infusion

Cited by 64 publications

References 12 publications

Bortezomib/docetaxel combination therapy in patients with anthracycline-pretreated advanced/metastatic breast cancer: a phase I/II dose-escalation study

Bortezomib/docetaxel combination therapy in patients with anthracycline-pretreated advanced/metastatic breast cancer: a phase I/II dose-escalation study

Therapeutic Drug Monitoring for the Individualization of Docetaxel Dosing: A Randomized Pharmacokinetic Study

Gemcitabine and Docetaxel in Metastatic Sarcoma: Past, Present, and Future

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