Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our aim was to establish, in patients with solid tumors, the dose-limiting toxicity, maximum tolerated dose (MTD), and pharmacology of PNU-145156E, a new sulfonated distamycin A derivative that blocked circulating angiogenesis-promoting growth factors in animal studies and exhibited an antitumor effect in murine solid tumors. In a Phase I study, PNU-145156E was administered i.v. every 6 weeks. Included were patients with solid tumors; an Eastern Cooperative Oncology Group performance score </=1; and normal bone marrow, renal, and liver functions and blood clotting tests. Excluded were patients with brain metastases or on steroid medication. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria. Plasma and urine PNU-145156E was measured for pharmacokinetic analysis. The effect of PNU-145156E on serum basic fibroblast growth factor (bFGF) was measured by sandwich ELISA. Twenty-nine patients (median age, 54 years; range, 33-71 years; 19 males and 10 females; median performance score = 1) were treated at dose levels of 100-1050 mg/m(2). We observed, during 47 treatment cycles, erratic but short-lasting decreases of antithrombin III levels (<75%) at all dose levels. Other clotting tests remained normal except during thromboembolic events. Dose-limiting toxicity was thrombophlebitis, pulmonary embolism, and grade 3 dyspnea. PNU-145156E disappeared from the circulation, decreasing triexponentially with a long terminal half-life of 1 month. No significant change in bFGF and no objective tumor responses were observed. Disease stabilization was achieved in four patients. In conclusion, the MTD of PNU-145156E was 1050 mg/m(2). Serum bFGF level was not affected by PNU-145156E up to the MTD.
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PMID:PNU-145156E, a novel angiogenesis inhibitor, in patients with solid tumors: a phase I and pharmacokinetic study. 1175 84