Tamoxifen, Carboplatin, and Topotecan in Treating Patients With CNS Metastases or Recurrent Brain or Spinal Cord Tumors

OBJECTIVES:

• To evaluate the systemic and CNS response rates and progression-free and overall survival of patients with epithelial cancer and brain metastases treated with tamoxifen citrate, topotecan hydrochloride, and carboplatin.
• To evaluate the response rates, progression-free survival, and overall survival of patients with recurrent primary glial tumors treated with this regimen.
• To further assess the toxicity of these drugs in these patients.
• To further evaluate the pharmacokinetics of topotecan hydrochloride and tamoxifen citrate using paired specimens of cerebrospinal fluid and plasma from these patients.

OUTLINE: Patients are stratified by disease type (epithelial CNS metastases vs recurrent glial tumors).

Patients receive topotecan IV on days 1-3 (72 hours), carboplatin IV over 30 minutes on day 4, and oral tamoxifen twice daily on days 1-7. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) may be treated for 2 additional courses after documentation of CR.

Patients undergo blood sample collection at baseline and then periodically after the first dose of topotecan to obtain plasma pharmacokinetic (PK) measurements of topotecan and tamoxifen. Some patients may also undergo cerebrospinal fluid (CSF) collection to assess peak CSF levels of topotecan and tamoxifen during course 1.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

• Epithelial neoplasms metastatic to the central nervous system

• Recurrent or refractory to prior chemotherapeutic or radiotherapeutic regimens or for which no standard chemotherapy or whole brain radiotherapy regimens exist
• Stage IV disease
• Recurrent glial tumors (brain or spinal cord)
• Received prior whole brain radiotherapy or stereotactic radiotherapy OR refused radiotherapy

• Patients with CNS metastases previously treated with radiotherapy are eligible, provided persistent or progressive CNS metastases are documented by MRI eight weeks after the end of radiotherapy
• Patients with glial tumors must show progressive disease by MRI after prior radiotherapy
• Measurable disease in the brain/leptomeninges of the brain or spinal cord with baseline documentation within 4 weeks of study entry

• Must have ≥ 1 lesion that is ≥ 1 cm on MRI scan
• Ineligible for or has refused participation in higher priority institutional protocols

PATIENT CHARACTERISTICS:

• Karnofsky performance status 50-100%
• Life expectancy ≥ 2 months
• Creatinine ≤ 1.5 mg/dL
• WBC 4,000/mm³ OR ANC ≥ 2,000/mm³
• Platelet count ≥ 150,000/mm³
• Bilirubin ≤ 1.5 mg/dL
• ALT and AST < 2 times upper limit of normal
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• No nonmalignant concurrent illness (e.g., cardiovascular or pulmonary) that is either poorly controlled with currently available treatment or of such severity to preclude study entry
• No severe infection
• Patients who are ineligible for lumbar puncture are allowed

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy, immunotherapy, or chemotherapy OR recovered from expected side effects of prior therapy
• No patients who are recovering from major surgery
• No concurrent radiotherapy
• Concurrent steroid or anticonvulsant therapy allowed