| Popis: |
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 Lv. every 6 weeks. Included were patients with solid tumors; an Eastern Cooperative Oncology Group performance score less than or equal to1; 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 ( |
