Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Sep 2016
Multicenter StudyPhase 1 study to evaluate the effect of the MEK inhibitor trametinib on cardiac repolarization in patients with solid tumours.
Trametinib is a reversible, selective inhibitor of the mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and 2 (MEK2). Cardiotoxicity (congestive heart failure, decreased heart rate, left ventricular dysfunction, and hypertension) related to trametinib is an infrequent, but serious, adverse event (AE). Prolongation of the QT interval increases the risk of life-threatening cardiac arrhythmia. Thus, the risk of trametinib inducing QT prolongation at putative supratherapeutic exposure was evaluated. ⋯ The results of this study suggest trametinib has no significant effect on QT prolongation at supratherapeutic exposure.
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Cancer Chemother. Pharmacol. · Sep 2016
Ethnic sensitivity assessment of the antibody-drug conjugate trastuzumab emtansine (T-DM1) in patients with HER2-positive locally advanced or metastatic breast cancer.
Trastuzumab emtansine (T-DM1) is indicated for previously treated HER2-positive metastatic breast cancer. Ethnic sensitivity assessment of T-DM1 was conducted using data from eight clinical studies to ensure that the clinically recommended dose is appropriate across ethnicities. ⋯ These results suggest that T-DM1 pharmacokinetics are comparable across ethnic groups and that use of the current dosing regimen is appropriate across ethnicities.
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Cancer Chemother. Pharmacol. · Aug 2016
A phase II study of nanoparticle albumin-bound paclitaxel plus carboplatin as the first-line therapy in elderly patients with previously untreated advanced non-small cell lung cancer.
The objective of this clinical trial was to explore the efficacy and tolerability of first-line chemotherapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel), a novel agent that uses a drug delivery system, plus carboplatin, in elderly Japanese patients with advanced non-small cell lung cancer (NSCLC). ⋯ UMIN-CTR identifier: UMIN000010738.
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Cancer Chemother. Pharmacol. · Aug 2016
A Phase I study of safety and pharmacokinetics of fruquintinib, a novel selective inhibitor of vascular endothelial growth factor receptor-1, -2, and -3 tyrosine kinases in Chinese patients with advanced solid tumors.
Fruquintinib (HMPL-013) is a novel oral small molecule compound that selectively inhibits vascular endothelial growth factor receptors-1, -2, and -3 with potent inhibitory effects on multiple human tumor xenografts. This first-in-human study was conducted to assess the maximum tolerated dose and dose-limiting toxicities, safety and tolerability, pharmacokinetics, and preliminary anti-tumor activity of fruquintinib. ⋯ Fruquintinib showed an acceptable safety profile and preliminary evidence of anti-tumor activity in patients with advanced solid tumors. The recommended dose was determined to be either 4 mg QD on a continuous regimen or 5 mg QD on a 3-week-on/1-week-off regimen.
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Cancer Chemother. Pharmacol. · Aug 2016
Multicenter StudyPanitumumab in combination with irinotecan plus S-1 (IRIS) as second-line therapy for metastatic colorectal cancer.
Irinotecan plus S-1 (IRIS) is the only oral fluoropyrimidine-based regimen reported to be non-inferior to FOLFIRI and widely used in clinical practice for metastatic colorectal cancer (mCRC) patients. However, the combination of IRIS plus an anti-EGFR agent has not been evaluated previously. This study aimed to investigate the feasibility and efficacy of IRIS with panitumumab as second-line therapy for wild-type KRAS mCRC. ⋯ IRIS plus panitumumab has an acceptable toxicity profile and a promising efficacy in patients with previously treated wild-type KRAS mCRC. Accordingly, this regimen can be an additional treatment option for second-line chemotherapy in wild-type KRAS mCRC.