Technetium Tc 99m sulfur colloid phenotypic probe for the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin in women with ovarian cancer.

Abstract

PURPOSE:

Significant variability in the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin (PLD) exists. PLD undergoes clearance via the mononuclear phagocyte system (MPS). Technetium Tc 99m sulfur colloid (TSC) is approved for imaging MPS cells. We investigated TSC as a phenotypic probe of PLD pharmacokinetics and pharmacodynamics in women with epithelial ovarian cancer.

METHODS:

TSC 10 mCi IVP was administered and followed by dynamic planar and SPECT/CT imaging and blood pharmacokinetics sampling. PLD 30-40 mg/m(2) IV was administered with or without carboplatin, followed by plasma pharmacokinetics sampling.

RESULTS:

There was a linear relationship between TSC clearance and encapsulated doxorubicin clearance (R(2) = 0.61, p = 0.02), particularly in patients receiving PLD alone (R(2) = 0.81, p = 0.04). There was a positive relationship (ρ = 0.81, p = 0.01) between maximum grade palmar-plantar erythrodysesthesia toxicity developed and estimated encapsulated doxorubicin concentration in hands.

CONCLUSIONS:

TSC is a phenotypic probe for PLD pharmacokinetics and pharmacodynamics and may be used to individualize PLD therapy in ovarian cancer and for other nanoparticles in development.

• Authors: Hugh Giovinazzo, Parag Kumar, Arif Sheikh, Kristina M Brooks, Marija Ivanovic, Mark Walsh, Whitney P Caron, Richard J Kowalsky, Gina Song, Ann Whitlow, Daniel L Clarke-Pearson, Wendy R Brewster, Linda Van Le, Beth A Zamboni, Victoria Bae-Jump, Paola A Gehrig, William C Zamboni
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 77 Issue 3 Pg. 565-73 (Mar 2016) ISSN: 1432-0843 [Electronic] Germany
• PMID: 26822231 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Radiopharmaceuticals
• liposomal doxorubicin
• Polyethylene Glycols
• Technetium Tc 99m Sulfur Colloid
• Doxorubicin
• Carboplatin

Topics

• Adult
• Aged
• Antibiotics, Antineoplastic (administration & dosage, adverse effects, pharmacokinetics)
• Carboplatin (administration & dosage)
• Carcinoma, Ovarian Epithelial
• Doxorubicin (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Female
• Hand-Foot Syndrome (etiology)
• Humans
• Middle Aged
• Neoplasms, Glandular and Epithelial (drug therapy, pathology)
• Ovarian Neoplasms (drug therapy, pathology)
• Phenotype
• Polyethylene Glycols (administration & dosage, adverse effects, pharmacokinetics)
• Radiopharmaceuticals (administration & dosage)
• Technetium Tc 99m Sulfur Colloid (administration & dosage)
• Tomography, Emission-Computed, Single-Photon (methods)
• Tomography, X-Ray Computed (methods)