TC > 0.05 as a Pharmacokinetic Parameter of Paclitaxel for Therapeutic Efficacy and Toxicity in Cancer Patients

Author(s): D.S. Xin, L. Zhou, C.Z. Li, S.Q. Zhang, H.Q. Huang, G.D. Qiu, L.F. Lin, Y.Q. She, J.T. Zheng, C. Chen, L. Fang, Z.S. Chen*, S.Y. Zhang*.

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Volume 13 , Issue 3 , 2018

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Abstract:

Background: Paclitaxel (PTX) has remarkable anti-tumor activity, but it causes severe toxicities. There is an urgent need to seek an appropriate pharmacokinetic parameter of PTX to improve treatment efficacy and reduce adverse effects.

Objective: To evaluate the association of pharmacokinetic parameter TC > 0.05 of paclitaxel (PTX) and its therapeutic efficacy and toxicity in patients with solid tumors.

Methods: A total of 295 patients with ovarian cancer, esophageal cancer, breast cancer, and non-small cell lung cancer (NSCLC), who were admitted to the Tumor Hospital of Shantou University Medical College, China, were recruited for this study. Patients received 3 weeks of PTX chemotherapy. The plasma concentrations of PTX were examined using the MyPaclitaxel™ kit. The patients’ PTX TC > 0.05 (the time during which PTX plasma concentration exceed 0.05µmol/L) were calculated based on pharmacokinetic analysis.

Results: The results showed that: (1) the concentrations of PTX in these 295 patients ranged from 0.0358-0.127 µmol/L; (2) the PTX TC > 0.05 ranged from 14 to 38h with a median time of 27h; (3) among all treatment cycles, there was a statistically significant difference in the PTX TC > 0.05 between CR+PR and SD+PD; (4) with the increasing value of TC > 0.05, level of leukopenia and leukopenic fever increased; (5) high PTX TC > 0.05 led to the occurrence of neutropenia, neutropenic fever, severe anemia, and severe peripheral neurotoxicity. Taken together, our results indicated that the pharmacokinetic parameter PTX TC > 0.05 was an effective measure of treatment efficacy and toxicity in patients with solid tumors. Maintaining PTX TC > 0.05 at 26 to 30h could improve its efficacy and reduce the incidence of leukopenia, neutropenia, anemia, and peripheral neurotoxicity in these patients.

Conclusion: PTX TC > 0.05 is a key pharmacokinetic parameter of PTX which should be monitored to optimize individual treatment in patients with solid tumors.

Keywords: Cancer treatment, paclitaxel, pharmacokinetics, TC > 0.05, therapeutic efficacy, toxicity.

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Article Details

VOLUME: 13
ISSUE: 3
Year: 2018
Page: [341 - 347]
Pages: 7
DOI: 10.2174/1574892813666180305170439
Price: $58

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