Publications (3)28.96 Total impact
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Article: CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib.
Journal of Clinical Oncology 03/2011; 29(15):e443-5. · 18.37 Impact Factor -
Article: Addition of gemcitabine at the time of sunitinib resistance in metastatic renal cell cancer.
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ABSTRACT: •To investigate the role of adding gemcitabine at the time of sunitinib failure in patients with metastatic renal cell cancer (mRCC). •A retrospective chart review of 13 patients with mRCC who experienced disease progression on sunitinib and received gemcitabine 750 mg/m(2) i.v. on days 1 and 8 and sunitinib 37.5 mg/day on days 2-15 every 21 days from September 2006-2009 was carried out. •Responses were assessed using the Response Evaluation Criteria in Solid Tumors. •The median age was 59, male to female ratio 10:3, Eastern Cooperative Oncology Group performance status 1-3; the number of prior regimens ranged from one to five, and duration on sunitinib alone ranged from 3 months to >1 year. •Twelve out of 13 patients received more than two cycles with one documented partial response, five stable disease and seven progressive disease. •The median time to progression was 21 weeks. •We documented grade 4 pulmonary emboli (n= 1), grade 3 neutropenia (n= 2), anaemia (n= 2) and thrombocytopenia (n= 1). •The combination of sunitinib and gemcitabine in patients with mRCC may delay disease progression in some patients exhibiting resistance to sunitinib. This regimen merits further prospective investigation in this patient population.BJU International 02/2011; 108(8 Pt 2):E245-9. · 2.84 Impact Factor -
Article: Phase I safety, pharmacokinetic, and pharmacodynamic study of ENMD-2076, a novel angiogenic and Aurora kinase inhibitor, in patients with advanced solid tumors.
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ABSTRACT: ENMD-2076 is a unique orally bioavailable Aurora kinase and VEGFR inhibitor. The purpose of this phase 1 study of ENMD-2076 was to determine the MTD, pharmacokinetic, and pharmacodynamic profiles and preliminary antitumor activity. Patients with refractory advanced solid malignancies were treated with ENMD-2076 orally with continuous once daily dosing. Doses from 60 to 200 mg/m(2) were evaluated using a standard 3 (to 4) + 3 design. Pharmacokinetic parameters were studied on days 1, 28, and 30 to 35 of cycle 1. Expanded MTD cohorts included patients with ovarian cancer, colorectal cancer, and refractory solid tumors. A total of 67 patients (46 F, 21M; ages 30-76) entered the study. Dose levels of 60, 80, 120, 200, and 160 mg/m(2) were evaluated. Two patients experienced grade 3 hypertension at 200 mg/m(2), and additional grade 3 neutropenia events limited tolerability at this dose. An intermediate dose of 160 mg/m(2) was determined to be the MTD. The most common drug-related adverse events included hypertension, nausea/vomiting, and fatigue. The pharmacokinetics of ENMD-2076 were characterized by a rapid absorption phase (T(max) 3-7.8 hours), a t(1/2) of 27.3 to 38.3 hours after a single dose, and dose proportional exposure. Decreased plasma sVEGFR2 was observed posttreatment. Two patients with platinum refractory/resistant ovarian cancer had RECIST partial responses. ENMD-2076 was well tolerated, had a linear pharmacokinetic profile, and showed promising antitumor activity, particularly in ovarian cancer. The recommended phase 2 dose of ENMD-2076 is 160 mg/m(2) administered orally once daily with continuous dosing.Clinical Cancer Research 02/2011; 17(4):849-60. · 7.74 Impact Factor
