Clinical Pharmacokinetics of Docetaxel

@article{Clarke1999ClinicalPO,
  title={Clinical Pharmacokinetics of Docetaxel},
  author={Stephen John Clarke and Laurent P. Rivory},
  journal={Clinical Pharmacokinetics},
  year={1999},
  volume={36},
  pages={99-114}
}
Docetaxel (Taxotere®), a semi-synthetic analog of paclitaxel (Taxol®), is a promoter of microtubule polymerization leading to cell cycle arrest at G2/M, apoptosis and cytotoxicity. Docetaxel has significant activity in breast, non-small-cell lung, ovarian and head and neck cancers.Docetaxel has undergone phase I study in a number of schedules, including different infusion durations and various treatment cycles. Doses studied in adults have ranged from 5 to 145 mg/m2 and those in children from… 
Clinical Pharmacokinetics of Docetaxel
TLDR
Strategies to individualise docetaxel administration schedules based on phenotypic or genotype-dependent differences in CYP3A expression are underway and may ultimately lead to more selective chemotherapeutic use of this agent.
Docetaxel: in gastric cancer.
TLDR
Combined therapy with docetaxel, cisplatin and fluorouracil was relatively well tolerated given the nature of chemotherapy in patients with metastatic or locally advanced/recurrent gastric or gastro-oesophageal junction adenocarcinoma.
Phase I study of vorinostat (suberoylanilide hydroxamic acid, NSC 701852) in combination with docetaxel in patients with advanced and relapsed solid malignancies
TLDR
The combination of vorinostat and docetaxel was poorly tolerated with excessive DLTs that required early study termination and the trial was stopped due to excessive toxicity.
A phase I and pharmacokinetic study of the nonpolyglutamatable thymidylate synthase inhibitor ZD9331 plus docetaxel in patients with advanced solid malignancies
TLDR
The combination regimen, consisting of ZD9331 and docetaxel, is feasible and well tolerated at single-agent doses that are clinically-relevant and does not appear to be associated with either major pharmacokinetic or toxicologic drug-drug interactions.
Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients
TLDR
Aprepitant at clinically recommended doses may have a low potential to affect the pharmacokinetics of intravenous chemotherapeutic agents metabolized by CYP3A4.
The orally administered P-glycoprotein inhibitor R101933 does not alter the plasma pharmacokinetics of docetaxel.
TLDR
Findings indicate that the contribution of a P-glycoprotein inhibitor to the activity of anticancer chemotherapy can now be assessed in patients for the first time independent of its effect on drug pharmacokinetics.
A clinical pharmacokinetic microdosing study of docetaxel with Japanese patients with cancer
TLDR
Docetaxel clearance showed marginal nonlinearity between microdose and therapeutic dose, presumably because of saturation of plasma protein binding; however, the magnitude was within twofold, allowing practically acceptable extrapolation.
Docetaxel: an update of its use in advanced breast cancer.
TLDR
Although no single standard regimen has been identified as optimal for the treatment of advanced breast cancer, phase III trials have shown that docetaxel has improved efficacy over doxorubicin alone, methotrexate/fluorouracil and mitomycin/vinblastine in second-line therapy.
Docetaxel: a review of its use in non-small cell lung cancer.
TLDR
Docetaxel is generally well tolerated by patients receiving treatment for locally advanced and metastatic NSCLC, and produces response and survival rates equivalent to many current standard treatment options, which are particularly encouraging in patients refractory or resistant to cisplatin or carboplatin.
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References

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TLDR
In vivo, the drug was found to be schedule independent and in vitro, the docetaxel concentrations required to reduce murine and human cell survival by 50% ranged from 4 to 35 ng/ml and the cytotoxic effects were greater on proliferating than on non-proliferating cells.
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Docetaxel has significant in vivo antitumor activity in the different models generally used for the preclinical evaluation of drugs and is cytotoxic at clinically relevant concentrations against fresh human tumor biopsy specimens in a soft agar cloning system.
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TLDR
It is concluded that using this schedule, a combination of docetaxel and vinorelbine can be administered in combination, together with granulocyte-colony stimulating factor, with a low risk of associated hematologic toxicity.
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TLDR
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TLDR
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PURPOSE This phase I study was performed to assess the feasibility of the combination of docetaxel and cisplatin and to determine the maximum-tolerated dose (MTD) and the side effects with an
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