Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Apr 2017
Multicenter StudyPhase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041).
This phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma. ⋯ The safety profile of pembrolizumab in Japanese patients was similar to that reported in the previous clinical studies. Pembrolizumab provided promising anti-tumor activity in Japanese patients with advanced melanoma.
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Cancer Chemother. Pharmacol. · Apr 2017
A phase 1 study of gemcitabine/nab-paclitaxel/S-1 (GAS) combination neoadjuvant chemotherapy for patients with locally advanced pancreatic adenocarcinoma.
To determine a recommended dose for a biweekly combination neoadjuvant chemotherapy including gemcitabine, nab-paclitaxel, and S-1 (GAS) for patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). ⋯ In conclusion, recommended doses for a biweekly GAS chemotherapy regimen were determined as nab-paclitaxel: 125 mg/m2, gemcitabine: 1000 mg/m2 on day 1, S-1: <1.25 m2, 60 mg; 1.25-1.5 m2, 80 mg; >1.5 m2, 100 mg twice a day on days 1-7. GAS chemotherapy showed good preliminary efficacy with mild toxicity in this study, and warrants a further phase 2 trial to investigate the efficacy of the GAS regimen for LAPC.
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Cancer Chemother. Pharmacol. · Mar 2017
Population pharmacokinetics of ABT-767 in BRCA1 or BRCA2 mutation carriers with advanced solid tumors or in subjects with high grade serous ovarian, primary peritoneal or fallopian tube cancer.
The objective of the manuscript is to describe the development of a population pharmacokinetic model for ABT-767, a potent and orally bioavailable inhibitor of poly (ADP-ribose) polymerase enzyme, and to evaluate the potential influence of patient demographics and baseline covariates on the pharmacokinetics of ABT-767. ⋯ Albumin on CL/F was the only statistically significant baseline covariate affecting ABT-767 pharmacokinetics, but it only explained a fraction of the pharmacokinetic variability. Dosage adjustments based on body size, age, or mild renal impairment are not needed for ABT-767. The developed model will be used to evaluate ABT-767 exposure-response analyses and to perform simulations for different dose and dosing regimens.
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Cancer Chemother. Pharmacol. · Jan 2017
A Phase I study of intravenous PI3K inhibitor copanlisib in Japanese patients with advanced or refractory solid tumors.
To evaluate the safety, tolerability, pharmacokinetics, and efficacy of the intravenously administered pan-PI3K inhibitor copanlisib in Japanese patients with advanced or refractory solid tumors. ⋯ NCT01404390.
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Cancer Chemother. Pharmacol. · Dec 2016
EGFR mutation status of paired cerebrospinal fluid and plasma samples in EGFR mutant non-small cell lung cancer with leptomeningeal metastases.
Central nervous system (CNS) is the prevalent site for metastases in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-relapsed NSCLC patients. To understand the EGFR mutation status in paired cerebrospinal fluid (CSF) and plasma samples after EGFR-TKI treatment failure might be useful to guide the treatment of intra- and extracranial tumors in those patients. ⋯ After EGFR-TKI failure, majority of the NSCLC patients with CNS metastases remained positive detection of EGFR sensitive mutations in CSF, but much less detection in the matched plasma. Significantly low exposure of gefitinib in CSF might explain the intracranial protection of the EGFR sensitive mutation positive tumor cells.