Topotecan and Radiation Therapy in Treating Patients With Solid Tumors or Lymphoma

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Esophageal Cancer; Lung Cancer; Lymphoma

Treatments: Drug: topotecan hydrochloride; Radiation: low-LET photon therapy; Radiation: low-LET electron therapy

Study type: Interventional

Funder types: NIH

Identifiers

NCT00002625

NCI-T94-0099C

WCCC-CO-9492

CDR0000063990 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

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 or lymphoma.

II. Assess the qualitative and quantitative nature of the toxic effects encountered in this treatment.

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.

OUTLINE:

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).

Enrollment: 5 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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 recovered
• At least 4 weeks since radiotherapy and recovered

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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5 participants in 1 patient group

Arm I

Experimental group

Description:

Radiosensitization plus Radiotherapy. Topotecan hydrochloride, TOPO, NSC-609699; plus external-beam irradiation using linear accelerators with photon energies between 4 and 10 MV (electrons acceptable for the boost field).

Treatment:

Radiation: low-LET electron therapy

Radiation: low-LET photon therapy

Drug: topotecan hydrochloride