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1.  A phase I study to determine the safety, pharmacokinetics and pharmacodynamics of a dual VEGFR and FGFR inhibitor, brivanib, in patients with advanced or metastatic solid tumors 
Annals of Oncology  2010;22(6):1413-1419.
Background: This study was designed to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of brivanib in patients with advanced/metastatic solid tumors.
Patients and methods: Ninety patients enrolled in this two-part, phase I open-label study of oral brivanib alaninate. The primary objectives of this study were (in part A) dose-limiting toxicity, maximum tolerated dose (MTD) and the lowest biologically active dose level and (in part B) the optimal dose/dose range. The secondary objectives of this study were preliminary evidence of antitumor activity, PK and PD.
Results: Across part A (open-label dose escalation and MTD) and part B (open-label dose optimization), 68 patients received brivanib alaninate. Brivanib demonstrated a manageable toxicity profile at doses of 180–800 mg. Most toxic effects were mild. Systemic exposure of the active moiety brivanib increased linearly ≤1000 mg/day. The MTD was 800 mg/day. Forty-four patients were treated at the MTD: 20 with 800 mg continuously, 11 with 800 mg intermittently and 13 with 400 mg b.i.d. doses. Partial responses were confirmed in two patients receiving brivanib ≥600 mg. Dynamic contrast-enhanced magnetic resonance imaging demonstrated statistically significant decreases in parameters reflecting tumor vascularity and permeability after multiple doses in the 800-mg continuous q.d. and 400-mg b.i.d. dose cohorts.
Conclusion: In patients with advanced/metastatic cancer, brivanib demonstrates promising antiangiogenic and antitumor activity and manageable toxicity at doses ≤800 mg orally q.d., the recommended phase II study dose.
PMCID: PMC3139984  PMID: 21131369
antiangiogenesis; brivanib; fibroblast growth factor; vascular endothelial growth factor
2.  A Phase I Study of an Oral Simulated FOLFOX with High Dose Capecitabine 
Investigational new drugs  2009;27(5):461-468.
A phase I study of high-dose capecitabine given over 2 days, along with oxaliplatin, bolus 5FU and leucovorin (LV), was designed to simulate FOLFOX6 without the need for infusional 5FU.
Schedule A included oxaliplatin 100 mg/m2, 5FU 400 mg/m2, and LV 20 mg/m2 (all given IV on days 1 and 15, 28 day cycle). Capecitabine was administered orally every 8 hours × 6 doses, days 1 and 15. Schedule B excluded 5FU and LV, maintaining oxaliplatin and capecitabine. Pharmacokinetics were performed for capecitabine for 6 patients on each schedule.
36 patients were treated. The dose-limiting toxicities seen included nausea, dehydration, fatigue, hypotension and confusion. Minimal palmar-plantar erythrodysesthesia was seen. Myelosuppression was common, but not a dose limiting toxicity. The pharmacokinetic parameters for capecitabine were unaltered.
Using capecitabine to mimic FOLFOX6 is feasible and well tolerated with a toxicity profile that differs from standard 14-day capecitabine dosing, with less palmar-plantar erythrodysesthesia. The phase II dose for capecitabine in combination with oxaliplatin, 5FU, and LV is 1500 mg/m2/dose or 2250 mg/m2/dose in the absence of bolus 5FU/LV.
PMCID: PMC2899673  PMID: 19129971
Capecitabine; oxaliplatin; 5-FU; chemotherapy; phase I
3.  Biologic features and treatment outcome of secondary acute lymphoblastic leukemia—a review of 101 cases 
Annals of Oncology  2008;19(9):1634-1638.
Background: Secondary acute lymphoblastic leukemia (sALL) is a rare disease and its biologic features are not well characterized.
Patients and methods: We describe a cohort of seven patients and discuss 94 additional cases from the literature for whom biological parameters were described. Cases with incomplete data were excluded.
Results: Hodgkin's disease (HD) was more common in the 18–59 age group while breast and prostate cancers were prevalent only in the ≥18-year-old patients. The time interval to develop sALL was similar among all age groups but was significantly longer for HD and neuroblastoma primary diagnoses and sALL with complex karyotype. T-cell immunophenotype was more common in the <18 age group. Complete remission was infrequent in the ≥60 age group. The overall survival was poor for all sALL regardless of age, primary diagnoses, cytogenetic subgroups, or immunophenotype. Allogeneic transplantation most probably represents the only chance of cure.
Conclusion: Better identification of prognostic factors to prevent the occurrence of sALL is indicated.
PMCID: PMC2733065  PMID: 18467310
acute lymphoblastic leukemia; 11q23 aberrations; secondary neoplasms

Results 1-3 (3)