Pharmacokinetics of liposomal doxorubicin (TLC-D99; Myocet) in patients with solid tumors: an open-label, single-dose study

@article{Mross2004PharmacokineticsOL,
  title={Pharmacokinetics of liposomal doxorubicin (TLC-D99; Myocet) in patients with solid tumors: an open-label, single-dose study},
  author={Klaus Mross and Bernward Niemann and Ulrich Massing and Joachim Drevs and Clemens Unger and Rupinder Bhamra and Christine E. Swenson},
  journal={Cancer Chemotherapy and Pharmacology},
  year={2004},
  volume={54},
  pages={514-524}
}
PurposeLiposomal encapsulation of doxorubicin is designed to increase safety and tolerability by decreasing cardiac and gastrointestinal toxicity through decreased exposure of these tissues to doxorubicin, while effectively delivering drug to the tumor. [] Key MethodExperimental designPatients received a single intravenous infusion of Myocet 75 mg/m2. Plasma samples were analyzed for concentration of liposome-encapsulated doxorubicin, total doxorubicin, and doxorubicinol.
Phase I study of non-pegylated liposomal doxorubicin in children with recurrent/refractory high-grade glioma
TLDR
The RD of Myocet® administered every 3 weeks to paediatric patients with high-grade glioma was 60 mg/m2 and the efficacy of the drug remains to be determined and should be studied in Phase II trials.
Phase I study of non-pegylated liposomal doxorubicin in combination with ifosfamide in adult patients with metastatic soft tissue sarcomas
TLDR
The combination of intravenous Myocet 40 mg/m2 on day 1 and ifosfamide 3,000 mg / m2 on days 1–3 every 3 weeks is safe and feasible; a phase II study is ongoing.
A phase IB dose-finding trial of liposomal doxorubicin in combination with capecitabine in patients with pretreated metastatic breast cancer
TLDR
Despite the lower cardiotoxicity of liposomal doxorubicin, the risk of cardiac damage persists in anthracycline-pretreated individuals and mandates close cardiac monitoring and careful evaluation of the overall cumulative dose.
Non-pegylated liposomal doxorubicin plus ifosfamide in metastatic soft tissue sarcoma: results from a phase-II trial.
TLDR
The combination of NPLD and ifosfamide reported in a population of metastatic soft tissue sarcoma patients at risk for developing heart failure encourage antitumour activity, similar to that of classical doxorubicin.
Liposomal Doxorubicin
TLDR
Liposomal doxorubicin represents an important advance in terms of offering reduced cardiotoxicity compared with conventionalDoxorUBicin, and can be used in preference to conventional doxorbicin in a combination regimen with cyclophosphamide in the first-line treatment of patients with metastatic breast cancer.
Hepatic arterial infusion in the treatment of liver metastases with PEG liposomes in combination with degradable starch microspheres (DSM) increases tumor 5-FU concentration. an animal study in CC-531 liver tumor-bearing rats.
TLDR
Liver intratumoral 5-FU concentration increases to >7,500 times that following i.v. administration by a combination of regional administration via the hepatic artery with temporary embolization by DSM and drug targeting by liposome-encapsulated 5-fu.
Liposomal Doxorubicin in Breast Cancer
TLDR
Improvements in cardiac toxicities and the improved efficacy have increased the potential of these liposomal formulations of doxorubicin for combination and sequencing with other biological and cytotoxic agents for clinical benefit.
...
...

References

SHOWING 1-10 OF 30 REFERENCES
Pharmacokinetics of doxorubicin administered i.v. as Myocet (TLC D-99; liposome-encapsulated doxorubicin citrate) compared with conventional doxorubicin when given in combination with cyclophosphamide in patients with metastatic breast cancer
TLDR
There was a correlation between the plasma AUC0−∞ of total doxorubicin and the degree of myelosuppression in patients receiving conventional doxorbicin, but this correlation was not found in patients received TLC D-99.
EORTC 10968: a phase I clinical and pharmacokinetic study of polyethylene glycol liposomal doxorubicin (Caelyx, Doxil) at a 6-week interval in patients with metastatic breast cancer. European Organization for Research and Treatment of Cancer.
TLDR
The recommended dose of Caelyx/Doxil using this schedule is 60 mg/m2 every 6 weeks, which is a safe and effective regimen that permits prolonged administration of anthracycline to patients with metastatic breast cancer.
Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer.
  • G. Batist, G. Ramakrishnan, L. Lee
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2001
TLDR
Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.
Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes.
TLDR
The results of this study are consistent with preclinical findings indicating that the pharmacokinetics of doxorubicin are drastically altered using Doxil and follow a pattern dictated by the liposome carrier.
Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer
TLDR
Findings show the important relationship between systemic exposure of doxorubicin and the degree of myelosuppression in patients with small cell lung cancer.
Skin toxic effects of polyethylene glycol-coated liposomal doxorubicin.
TLDR
The profile of toxic effects of Doxil to the skin reflects its unique pharmacokinetics and tissue distribution, and skin reactions vary significantly from those associated with doxorubicin in non-liposome-encapsulated form.
Doxorubicin and doxorubicinol: intra-and inter-individual variations of pharmacokinetic parameters
TLDR
A model for curve-fitting of these metabolite plasma concentrations that is based on two successive releases of the compound in the plasma compartment, separated by a lag time is proposed.
Phase I and pharmacokinetic study of a stable, polyethylene‐glycolated liposomal doxorubicin in patients with solid tumors
TLDR
A Phase I study of a stable liposomal doxorubicin with polyethylene glycol (PEG) coating and phospholipid component of distearoyl phosphatidylcholine (DSPC) was performed to characterize its pharmacokinetic properties, toxicity profile, and maximal tolerated dose.
Pharmacokinetics and metabolism of anthracyclines.
TLDR
The new anthracyclines of clinical interest in solid tumours are more lipophilic than doxorubicin and have a higher volume of distribution and an increased total plasma clearance, and are of particular interest for locoregional therapy, especially through the hepatic artery.
Correlation of toxicity with pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in metastatic breast carcinoma
Doxil (ALZA Corp., Mountain View, CA) is a formulation of doxorubicin in polyethylene‐glycol coated liposomes with a prolonged circulation time and unique toxicity profile. As yet, the effect of the
...
...