Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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Multicenter Study
Safety, pharmacokinetic, and pharmacodynamic phase I dose-escalation trial of PF-00562271, an inhibitor of focal adhesion kinase, in advanced solid tumors.
PF-00562271 is a novel inhibitor of focal adhesion kinase (FAK). The objectives of this study were to identify the recommended phase II dose (RP2D) and assess safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of PF-00562271. ⋯ The MTD and RP2D of PF-00562271 is 125 mg twice per day with food. PF-00562271 displayed time- and dose-dependent nonlinear PK and is likely a potent CYP 3A inhibitor. This first-in-class study supports further investigation of FAK as a promising therapeutic target.
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Multicenter Study
Anthracycline-related cardiomyopathy after childhood cancer: role of polymorphisms in carbonyl reductase genes--a report from the Children's Oncology Group.
Carbonyl reductases (CBRs) catalyze reduction of anthracyclines to cardiotoxic alcohol metabolites. Polymorphisms in CBR1 and CBR3 influence synthesis of these metabolites. We examined whether single nucleotide polymorphisms in CBR1 (CBR1 1096G>A) and/or CBR3 (CBR3 V244M) modified the dose-dependent risk of anthracycline-related cardiomyopathy in childhood cancer survivors. ⋯ This study demonstrates increased anthracycline-related cardiomyopathy risk at doses as low as 101 to 150 mg/m(2). Homozygosis for G allele in CBR3 contributes to increased cardiomyopathy risk associated with low- to moderate-dose anthracyclines, such that there seems to be no safe dose for patients homozygous for the CBR3 V244M G allele. These results suggest a need for targeted intervention for those at increased risk of cardiomyopathy.
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Our aim was to analyze and validate the prognostic impact of the novel International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) proposal for an architectural classification of invasive pulmonary adenocarcinomas (ADCs) across all tumor stages. ⋯ Besides all recent molecular progress, architectural grading of pulmonary ADCs according to the novel IASLC/ATS/ERS scheme is a rapid, straightforward, and efficient discriminator for patient prognosis and may support patient stratification for adjuvant chemoradiotherapy. It should be part of an integrated clinical, morphologic, and molecular subtyping to further improve ADC treatment.
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Evidence has suggested a clinically meaningful relationship between self-reported quality of life (QOL) of a patient with cancer at the time of receiving a cancer diagnosis and overall survival (OS). This study evaluated the prognostic value of QOL assessments with regard to OS in a large cohort of patients with lung cancer. ⋯ Overall QOL measured by a simple single item at the time of lung cancer diagnosis is a significant and independent prognostic factor for survival in patients with lung cancer.