Docetaxel and Temozolomide in Treating Patients With Metastatic Cancer

OBJECTIVES:

Primary

• Determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of docetaxel and temozolomide (TMZ) in patients with metastatic cancer.

Secondary

• Determine the activity of docetaxel and TMZ in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive docetaxel IV over 1 hour on days 1, 8, and 15 and oral temozolomide once daily on days 1-21. Treatment repeats every 28 days for up to 1 year in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of docetaxel and temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 6 patients receive treatment at the MTD.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed diagnosis of a nonhematologic malignancy that is refractory to standard therapy OR for which no standard therapy is available
• Measurable (by CT scan) or evaluable disease

• If palliative radiotherapy has been administered, the measurable disease must be outside the radiation port
• Prior brain metastasis allowed provided it was definitely treated with external-beam radiotherapy, gamma knife, or surgical resection and is clinically stable

• Repeat MRI or CT scans must demonstrate stabilization of disease 4 weeks after the definitive therapy is completed AND there must be no requirement for dexamethasone
• No active CNS metastasis

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 4 months
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 8.0 g/dL (epoetin alfa and/or transfusions allowed)
• Creatinine ≤ 2 mg/dL
• Bilirubin normal
• PT normal, unless the patient is on warfarin for prior deep vein thrombosis or pulmonary embolus, requiring INR maintained at 2.0 - 3.0
• Sodium and potassium normal
• AST and ALT ≤ 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN
• No decompensated cardiac arrhythmia or other severe cardiovascular disease (i.e., New York Heart Association [NYHA] class III-IV heart disease)

• Patients with clinically stable NYHA class III or IV heart disease require cardiac clearance
• No peripheral neuropathy > grade 1
• No infection requiring IV antibiotics within the past 14 days
• No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
• No HIV positivity
• No hepatitis B surface antigen or hepatitis C antibody positivity
• No pulmonary embolus within the past 3 weeks
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 methods of effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No more than 3 courses of prior immunotherapy and/or chemotherapy for metastatic disease

• Interferon alfa in the adjuvant setting is not considered a course of prior therapy

• Patients who relapse on adjuvant interferon alfa must be off therapy for ≥ 3 weeks
• No prior stem cell or organ transplantation
• More than 21 days since prior immunotherapy or chemotherapy
• At least 21 days since prior hormonal therapy (except luteinizing hormone-releasing hormone [LHRH] agonists) or radiotherapy and recovered
• More than 21 days since prior surgery requiring general anesthesia
• No concurrent radiotherapy
• Concurrent LHRH agonist therapy allowed
• Concurrent physiologic replacement steroids allowed
• No other concurrent chemotherapy or thalidomide
• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) during study chemotherapy