Phase I trial to study the effectiveness of topotecan and radiation therapy in treating
patients who have solid tumors or lymphoma. Drugs used in chemotherapy use different ways to
stop cancer cells from dividing so they stop growing or die. Radiation therapy uses
high-energy x-rays to damage cancer cells. Combining chemotherapy with radiation therapy may
kill more cancer cells.
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).
- Microscopically confirmed solid tumor or lymphoma not potentially curable by
conventional surgery or radiotherapy
- Previously unirradiated disease scheduled to receive thoracic irradiation of up to 60
Gy, including pulmonary and esophageal tumors
- No metastatic disease more effectively treated by systemic chemotherapy
- No history of brain metastases
- Age: 18 and over
- Performance status: ECOG 0 or 1
- WBC at least 4,000
- ANC at least 1,500
- Platelets at least 100,000
- Bilirubin no greater than 1.5 mg/dL
- Creatinine no greater than 1.5 mg/dL
- Calcium no greater than 11.0 mg/dL
- No pregnant or nursing women
- Pregnancy test required, as appropriate
- Effective contraception required of fertile patient
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since chemotherapy (6 weeks since nitrosoureas and mitomycin) and
- At least 4 weeks since radiotherapy and recovered