PHASE I STUDY OF TOPOTECAN AND THORACIC RADIATION
I. Define the maximum tolerated dose and safety profile of topotecan (TOPO) administered
with daily high-dose thoracic radiotherapy to a total of 60 Gy in patients with solid tumor
II. Assess the qualitative and quantitative nature of the toxic effects encountered in this
III. Estimate the tissue and tumor TOPO concentrations during radiotherapy by evaluating
plasma TOPO levels.
IV. Evaluate, using Western blot and immunohistochemical stain, the effects of
TOPO/radiotherapy on topoisomerase I levels in peripheral blood lymphocytes (PBL).
V. Determine whether TOPO induces apoptosis in PBL from this patient population.
VI. Examine tumor tissue pre- and post-treatment (if available) for topoisomerase I levels,
DNA damage, topoisomerase I/DNA complexes, and apoptotic events.
Radiosensitization plus Radiotherapy. Topotecan, TOPO, NSC-609699; plus external-beam
irradiation using linear accelerators with photon energies between 4 and 10 MV (electrons
acceptable for the boost field).
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
George Wilding, MD
University of Wisconsin, Madison
United States: Food and Drug Administration
|University of Wisconsin Comprehensive Cancer Center||Madison, Wisconsin 53792|