Kathryn E Mazina

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3020 Background: The PI3K-AKT-mTOR signaling pathway is deregulated in a wide variety of cancers. GDC-0980 is a potent, selective, oral inhibitor of class I PI3K and mTOR kinase with in vitro IC50 of 4.8 nM for p110α/p85α and apparent Ki of 17.3 nM for human mTOR. GDC-0980 demonstrates broad activity in xenograft cancer models (breast, ovarian, lung, and(More)
PURPOSE This first-in-human dose-escalation trial evaluated the safety, tolerability, maximal-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, pharmacodynamics, and preliminary clinical activity of pictilisib (GDC-0941), an oral, potent, and selective inhibitor of the class I phosphatidylinositol-3-kinases (PI3K). PATIENTS AND(More)
Nasal congestion in allergic rhinitis results from tissue edema and vasodilatation in the nasal mucosa. Of the mediators released by mast cells in response to allergens, prostaglandin (PG) D2 is regarded as the most potent inducer of nasal congestion. Intranasal administration of PGD2 reproduces the nasal blockade experienced by patients with seasonal(More)
PURPOSE This phase I study, conducted in advanced-stage cancer patients, assessed the safety and tolerability of oral vorinostat (suberoylanilide hydroxamic acid), single-dose and multiple-dose pharmacokinetics of vorinostat, and the effect of a high-fat meal on vorinostat pharmacokinetics. EXPERIMENTAL DESIGN Patients (n = 23) received single doses of(More)
Farnesyl:protein transferase (FPTase) inhibitors were developed as anti-Ras drugs, but they fail to inhibit Ki-Ras activity because Ki-Ras can be modified by geranylgeranyl:protein transferase type-I (GGPTase-I). L-778,123, an inhibitor of FPTase and GGPTase-I, was developed in part because it can completely inhibit Ki-Ras prenylation. To support the(More)
3501 Background: The PI3K-PTEN-AKT signaling pathway is deregulated in a wide variety of cancers. GDC-0941 is a potent and selective oral inhibitor of the class I PI3K with 3 nM IC50 for the p110-alpha subunit in vitro and 28 nM IC50 in a cell-based pAKT assay and demonstrates broad activity in breast, ovarian, lung, and prostate cancer models. METHODS A(More)
3538 Background: The PI3K-PTEN-AKT signaling pathway is deregulated in a wide variety of cancers. GDC-0941 is a potent and selective oral inhibitor of class I PI3K and demonstrates activity in a broad range of preclinical models (breast, ovarian, lung, and prostate). METHODS Patients (pts) with histologically confirmed advanced solid tumors and ECOG PS(More)
This Phase I study was performed to assess the feasibility of administering L-778,123, a peptidomimetic farnesyl protein transferase (FPTase) inhibitor, as a continuous i.v. infusion for 7 days every 3 weeks and to determine the recommended dose for subsequent disease-directed trials. This study also sought to characterize the pharmacological behavior of(More)
3021 Background: The PI3K-PTEN-AKT signaling pathway is deregulated in a wide variety of cancers. GDC-0941 is a potent inhibitor of class I PI3K and demonstrates broad activity in preclinical xenograft models. METHODS A 2-stage phase I study of GDC-0941 was initiated (GDC4254g). Stage 1 utilized a 3+3 escalation design in patients (pts) with advanced(More)
3052^ Background: The PI3K-PTEN-AKT signaling pathway is deregulated in a wide variety of cancers. GDC-0941 is a potent, oral, selective pan-inhibitor of class I PI3K with IC50 against the isoforms of p110 ranging from 3 nM (p110α) to 75 nM (p110γ) in vitro. METHODS A 2-stage phase I dose-escalation study (GDC4255g) using a 3+3 design was initiated in(More)
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