Publications by authors named "Carlyn Rose C Tan"

3 Publications

  • Page 1 of 1

Clinical Pharmacokinetics and Pharmacodynamics of Bortezomib.

Clin Pharmacokinet 2019 02;58(2):157-168

Department of Hematology/Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA.

Proteasome inhibitors disrupt multiple pathways in cells and the bone marrow microenvironment, resulting in apoptosis and inhibition of cell-cycle progression, angiogenesis, and proliferation. Bortezomib is a first-in-class proteasome inhibitor approved for the treatment of multiple myeloma and mantle cell lymphoma after one prior therapy. It is also effective in other plasma cell disorders and non-Hodgkin lymphomas. The main mechanism of action of bortezomib is to inhibit the chymotrypsin-like site of the 20S proteolytic core within the 26S proteasome, thereby inducing cell-cycle arrest and apoptosis. The pharmacokinetic profile of intravenous bortezomib is characterized by a two-compartment model with a rapid initial distribution phase followed by a longer elimination phase and a large volume of distribution. Bortezomib is available for subcutaneous and intravenous administration. Pharmacokinetic studies comparing subcutaneous and intravenous bortezomib demonstrated that systemic exposure was equivalent for both routes; pharmacodynamic parameters of 20S proteasome inhibition were also similar. Renal impairment does not influence the intrinsic pharmacokinetics of bortezomib. However, moderate or severe hepatic impairment causes an increase in plasma concentrations of bortezomib. Therefore, patients with moderate or severe hepatic impairment should start at a reduced dose. Because bortezomib undergoes extensive metabolism by hepatic cytochrome P450 3A4 and 2C19 enzymes, certain strong cytochrome P450 3A4 inducers and inhibitors can also alter the systemic exposure of bortezomib. This article critically reviews and summarizes the clinical pharmacokinetics and pharmacodynamics of bortezomib at various dosing levels and routes of administration as well as in specific patient subsets. In addition, we discuss the clinical efficacy and safety of bortezomib.
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http://dx.doi.org/10.1007/s40262-018-0679-9DOI Listing
February 2019

Combination antiretroviral therapy accelerates immune recovery in patients with HIV-related lymphoma treated with EPOCH: a comparison within one prospective trial AMC034.

Leuk Lymphoma 2018 08 21;59(8):1851-1860. Epub 2017 Nov 21.

e Department of Medicine , Memorial Sloan-Kettering Cancer Center/Weill-Cornell Medical College , New York , NY , USA.

Drug-drug interactions between cART and chemotherapy may impact HIV and lymphoma control or lead to increased toxicities. No prospective comparative data informs potential harms and benefits. In AMC034, HIV-associated high-grade B-cell NHL patients received DA-EPOCH with rituximab. cART was given with EPOCH or delayed until chemotherapy completion per investigator choice. Pharmacokinetic, immunological, and treatment effects of concurrent cART were evaluated. CD4 counts dropped during EPOCH in both groups but recovered to higher than baseline 6 months post-EPOCH only in the cART group. HIV viral load decreased during chemotherapy in the cART group but increased in the non-cART group. Incidence of grade ≥3 infectious, hematologic, or neurological toxicities was similar. Concurrent cART was not associated with 1-year EFS or OS. cART with EPOCH was well-tolerated and allowed for faster immune recovery. While we did not observe differences in outcome, the preponderance of evidence is in favor of combining cART with chemotherapy.
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http://dx.doi.org/10.1080/10428194.2017.1403597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962410PMC
August 2018

Circulating Tumor Cells Versus Circulating Tumor DNA in Colorectal Cancer: Pros and Cons.

Curr Colorectal Cancer Rep 2016 Jun 7;12(3):151-161. Epub 2016 Apr 7.

Department of Hematology/Oncology and Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.

Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are emerging noninvasive multifunctional biomarkers in liquid biopsy allowing for early diagnosis, accurate prognosis, therapeutic target selection, spatiotemporal monitoring of metastasis, as well as monitoring response and resistance to treatment. CTCs and ctDNA are released from different tumor types at different stages and contribute complementary information for clinical decision. Although big strides have been taken in technology development for detection, isolation and characterization of CTCs and sensitive and specific detection of ctDNA, CTC-, and ctDNA-based liquid biopsies may not be widely adopted for routine cancer patient care until the suitability, accuracy, and reliability of these tests are validated and more standardized protocols are corroborated in large, independent, prospectively designed trials. This review covers CTC- and ctDNA-related technologies and their application in colorectal cancer. The promise of CTC-and ctDNA-based liquid biopsies is envisioned.
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http://dx.doi.org/10.1007/s11888-016-0320-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976692PMC
June 2016