Kimberly A. Binger

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We conducted a phase I dose-escalation trial of perillyl alcohol (POH; NSC 641066) given p.o. on a continuous four times a day basis to characterize the maximum tolerated dose, toxicities, pharmacokinetic profile, and antitumor activity. Sixteen evaluable patients with advanced refractory malignancies were treated at the following doses: level 1 (L1), 800(More)
Abstract Purpose. Flavopiridol (NSC 649890) is a synthetic flavone possessing significant antitumor activity in preclinical models. Flavopiridol is capable of inducing cell cycle arrest and apoptosis, presumably through its potent, specific inhibition of cyclin-dependent kinases. We conducted a phase I trial and pharmacokinetic study of flavopiridol given(More)
7194 Background: The EGFR is often overexpressed in advanced non-small-cell lung cancer (NSCLC) - a solid tumor associated with a poor prognosis. Oncogenic k-ras mutations and raised serum VEGF predict poor outcome in NSCLC. In vitro targets of sorafenib include Raf, which is downstream of EGFR and k-ras. Sorafenib also targets the VEGFR-2/-3 tyrosine(More)
Purpose: To evaluate the clinical tolerability of a new schedule of 6-hydroxymethylacylfulvene (irofulven, MGI 114, HMAF, NSC 683863), a semisynthetic sesquiterpene derived from the cytotoxic mushroom metabolite illudin S. Irofulven has been shown to induce DNA damage and apoptosis in vitro and has shown activity in a number of human tumor xenograft models.(More)
Previous experience with perillyl alcohol (POH) was with a formulation of 500-mg capsules each containing 250 mg POH and soybean oil. This formulation resulted in the ingestion of large amounts of soybean oil (>10 g/day). Dose-limiting toxicities (DLT) were primarily gastrointestinal. Prior studies also showed no further increase in POH metabolite(More)
This phase I trial sought to define the toxicity, maximally tolerated dose (MTD) and pharmacodynamics of a combination of bortezomib and doxorubicin in patients with advanced malignancies. Twenty-six patients were treated with bortezomib intravenously on days 1, 4, 8 and 11, with doxorubicin also administered intravenously on days 1 and 8, both in a 21-day(More)
PURPOSE To assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacodynamics, and antitumor activity of continuous weekly-administered paclitaxel and BMS-214662, a novel farnesyl transferase inhibitor. EXPERIMENTAL DESIGN Patients were treated every week as tolerated with i.v. paclitaxel (fixed dose, 80 mg/m(2)/wk) administered over(More)
Sunitinib treatment results in a compensatory increase in plasma VEGF levels. Acute withdrawal of sunitinib results in a proliferative withdrawal flare, primarily due to elevated VEGF levels. Concurrent sunitinib plus bevacizumab is poorly tolerated with high (37 %) incidence of microangiopathic hemolytic anemia (MAHA). We evaluated a sequential design(More)
Piritrexim is a new antifolate that has shown activity in methotrexate-resistant tumors. Gemcitabine is an antimetabolite similar in structure to cytosine arabinoside with early studies demonstrating activity in a variety of cancers. It also has apparent synergistic activity with antifolates from initial work in tumor models. Paclitaxel is an(More)
2024 Background: Similar to taxanes, epothilones are a class of naturally occurring cytotoxic macrolides that stabilize microtubules and induce mitotic arrest, retaining potency in P-glycoprotein MDR cell lines. 6 schedules of KOS-862 were investigated in phase I trials. METHODS As the optimal schedule in the mouse xenograft model used prolonged exposure(More)