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Are Doses and Schedules of Small-Molecule Targeted Anticancer Drugs Recommended by Phase I Studies Realistic?
(AMER ASSOC CANCER RESEARCH, 2016-05-01)
Tolerability of molecularly targeted agents (MTA) used in cancer therapeutics is determined in phase I trials. We reviewed the reported incidence of toxicity in phase III trials at doses and schedules recommended by phase ...
A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies.
(2016-04)
Background The kinase activity of mTOR involves 2 multiprotein complexes, (mTORC1-mTORC2). Targeting mTORC1 with rapalogues induces compensatory feedback loops resulting in AKT/ERK activation, which may be abrogated by ...
Fatigue in Advanced Cancer Patients: Congruence Between Patients and Their Informal Caregivers About Patients' Fatigue Severity During Cancer Treatment With Palliative Intent and Predictors of Agreement.
(2016-09)
Context Informal caregivers (ICs) are increasingly involved in the monitoring of symptoms during advanced cancer patients' treatment with palliative intent. A common but subjective symptom during this extended treatment ...
CDK4/6 Inhibitors: Promising Opportunities beyond Breast Cancer.
(2016-07)
Patnaik and colleagues report on the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of abemaciclib for the treatment of advanced solid cancers, demonstrating antitumor activity in advanced breast ...
Hyperglycemia and Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin (PI3K/AKT/mTOR) Inhibitors in Phase I Trials: Incidence, Predictive Factors, and Management.
(ALPHAMED PRESS, 2016-07-01)
BACKGROUND: Dysregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is implicated in human cancer growth and progression. Agents targeting this pathway are ...
Clinical development of new drug-radiotherapy combinations.
(NATURE PUBLISHING GROUP, 2016-10-01)
In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures ...
Critical parameters in targeted drug development: the pharmacological audit trail.
(W B SAUNDERS CO-ELSEVIER INC, 2016-08-01)
The Pharmacological Audit Trail (PhAT) comprises a set of critical questions that need to be asked during discovery and development of an anticancer drug. Key aspects include: (1) defining a patient population; (2) ...
A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours.
(ELSEVIER SCI LTD, 2016-11-01)
PURPOSE: We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, ...