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

[ Vol. 13 , Issue. 3 ]

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* and S.Y. Zhang*   Pages 341 - 347 ( 7 )

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.

Affiliation:

Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Raoping Rd, Shantou 515041, Guangdong, Department of Gynecologic Oncology, Cancer Hospital of Shantou University Medical College, Raoping Rd, Shantou 515041, Guangdong, Department of Gynecologic Oncology, Cancer Hospital of Shantou University Medical College, Raoping Rd, Shantou 515041, Guangdong, Medical Oncology, Cancer Hospital of Shantou University Medical College, Raoping Rd, Shantou, Guangdong, 515041, Department of Ultrasound, Cancer Hospital of Shantou University Medical College, Raoping Rd, Shantou 515041, Guangdong, Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Raoping Rd, Shantou 515041, Guangdong, Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Raoping Rd, Shantou 515041, Guangdong, Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Raoping Rd, Shantou 515041, Guangdong, Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Raoping Rd, Shantou 515041, Guangdong, Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Raoping Rd, Shantou 515041, Guangdong, Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Raoping Rd, Shantou 515041, Guangdong, Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John`s University, 8000 Utopia Parkway, Queens, NY 11439, Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Raoping Rd, Shantou 515041, Guangdong



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