Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Jan 2013
Meta AnalysisPharmacokinetic-pharmacodynamic relationship of bosutinib in patients with chronic phase chronic myeloid leukemia.
Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor that has demonstrated manageable safety and high response rates in patients with chronic phase (CP) chronic myeloid leukemia (CML). The current analysis evaluated potential bosutinib pharmacokinetic-pharmacodynamic relationships. ⋯ The absence of exposure-response relationships for some safety and efficacy metrics may reflect bosutinib exposure metrics that exceeded the half-maximal inhibitory values and achieved a maximum effect.
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Cancer Chemother. Pharmacol. · Jan 2013
Controlled Clinical TrialEvaluation of the pharmacokinetics and safety of bosutinib in patients with chronic hepatic impairment and matched healthy subjects.
Bosutinib, a dual Src/Abl kinase inhibitor in development for treatment of chronic myeloid leukemia, is primarily metabolized by the CYP3A4 hepatic enzyme. This study evaluated the pharmacokinetics and safety of bosutinib in patients with chronic hepatic impairment and matched healthy subjects. ⋯ A single oral dose of bosutinib 200 mg showed acceptable tolerability in healthy subjects and in patients with mild, moderate, or severe chronic hepatic impairment.
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Cancer Chemother. Pharmacol. · Jan 2013
Multicenter StudyEffect of abiraterone acetate plus prednisone on the pharmacokinetics of dextromethorphan and theophylline in patients with metastatic castration-resistant prostate cancer.
To assess the effect of abiraterone acetate plus prednisone on the pharmacokinetics of dextromethorphan HBr (CYP2D6 substrate) and theophylline (CYP1A2 substrate) in patients with metastatic castration-resistant prostate cancer (mCRPC). ⋯ Abiraterone acetate plus prednisone increased the exposure of dextromethorphan, suggesting a need for caution when coadministrating with known CYP2D6 substrates. The pharmacokinetics of theophylline was unaffected when coadministered with abiraterone acetate plus prednisone.
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Cancer Chemother. Pharmacol. · Jan 2013
Effects of tumor type, degree of obesity, and chemotherapy regimen on chemotherapy dose intensity in obese cancer patients.
The American Society of Clinical Oncology recently published a Clinical Practice Guideline entitled "Appropriate Chemotherapy Dosing for Obesity Adult Patients with Cancer." The panel recommended that full weight (actual weight)-based cytotoxic chemotherapy doses are used to treat obese patients with cancer, particularly when the goal of treatment is cure. However, no study has examined dosage calculation methods used for obese cancer patients in Japan. Here, we retrospectively studied the relationships between chemotherapy dose intensity, the occurrence of adverse events, and treatment outcomes in obese patients undergoing chemotherapy. ⋯ In solid tumor patients with ≥30 body mass index (BMI), the incidence of Grade 3/4 hematological toxicity was significantly lower in the ideal BWg than in the actual BWg. Particularly, in patients with complications, incidence of Grade 4 hematological toxicity was significantly higher in the actual BWg than in the ideal BWg. These results suggest that the tumor type, degree of obesity, complications, and choice of chemotherapy regimen should be considered when determining chemotherapy dosage for obese patients.