Age-Related Changes in Nanoparticle Albumin-Bound Paclitaxel Pharmacokinetics and Pharmacodynamics: Influence of Chronological Versus Functional Age.

Autor:	Hurria, Arti, Blanchard, M. Suzette, Synold, Timothy W., Mortimer, Joanne, Chung, Cathie T., Luu, Thehang, Katheria, Vani, Rotter, Arnold J., Wong, Carol, Choi, Anthony, Feng, Tao, Ramani, Rupal, Doan, Caroline M., Brown, Jaycen, Somlo, George
Předmět:	AGE distribution BREAST tumors CANCER chemotherapy CLINICAL trials CONFIDENCE intervals FISHER exact test LIQUID chromatography MASS spectrometry METASTASIS NANOPARTICLES PACLITAXEL QUESTIONNAIRES REGRESSION analysis RESEARCH funding STATISTICS T-test (Statistics) DATA analysis ALBUMINS TREATMENT effectiveness DESCRIPTIVE statistics KAPLAN-Meier estimator KARNOFSKY Performance Status PHARMACODYNAMICS
Zdroj:	Oncologist; Jan2015, Vol. 20 Issue 1, following p37-44, 10p
Abstrakt:	Purpose. This study evaluated age-related changes in pharmacokinetic and pharmacodynamic parameters of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in patients with metastatic breast cancer. Methods. Forty patients received nab-paclitaxel (100 mg/m2 weekly for 3 weeks followed by a 1-week break) as first- or second-line chemotherapy. Blood samples were collected for analysis, and response was assessed every two cycles. Planned statistical analyses included linear regression to examine the relationship between age and pharmacokinetic variables (ln clearance [CL] andln areaunder the curve [AUC]) andtwo-sided two-sample t tests to evaluate age differences in pharmacodynamic variables. The association between chemotherapy toxicity risk scores and pharmacokinetic and pharmacodynamic variables including grade$3 toxicity were examined post hoc. Results. Of 40 patients enrolled, 39 (98%) were evaluable (mean age: 60 years; range: 30-81 years). A partial response was achieved in 31%, and 38% had stable disease. There was a borderline positive association between age and 24-hour ln AUC (slope50.011; SE50.006; p5.055). Grade 3 toxicitywas experienced by 26% (8% hematologic, 18% nonhematologic). Therewerenodifferences inage basedonthe presence ofgrade 3toxicity (p5.75), dose reductions (p5.38), ordose omissions (p 5 .15). A significant association was noted between chemotherapy toxicity risk score category and presence of grade 3 toxicity (toxicity rate by risk score category: low, 5 of 30 patients;medium,3of6patients; high,2of3patients;p5.041). Conclusion. A borderline significant relationship exists between age and 24-hour AUC, but no differences were noted for pharmacodynamic variables (grade 3 toxicity, dose reductions, or dose omissions) based on age. There is an association between toxicity risk score and grade $3 chemotherapy toxicity and pharmacokinetic variables. The treatment is well tolerated across all age groups. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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