2-methoxyestradiol in treating patients with advanced solid tumors

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: 2-methoxyestradiol may stop the growth of cancer by stopping blood flow to the tumor. purpose: phase i trial to study the effectiveness of 2-methoxyestradiol in treating patients who have advanced solid tumors.

objectives: * determine the maximum tolerated dose of 2-methoxyestradiol in patients with advanced solid tumors. * determine the side effect profile of this drug in these patients. * determine the pharmacokinetic profile of this drug in these patients. * determine the changes in positron-emission tomography scans of patients treated with this drug. * determine the changes in apotosis in patients treated with this drug. outline: this is a dose-escalation study. patients receive oral 2-methoxyestradiol (2me2) once on day 1 followed by 2 days of evaluation. patients then receive oral 2me2 every 12 hours. treatment continues in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of 2me2 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed at day 30. projected accrual: a total of 30 patients will be accrued for this study within 1 year.

Eligibility criteria:
disease characteristics: * histologically confirmed solid tumor * metastatic or unresectable disease for which standard curative treatments do not exist or are no longer effective * clinically progressive disease documented by any of the following: * new area of malignant disease * progression of soft-tissue metastases * at least 1 new metastatic deposit on technetium tc 99m bone scintigraphy * increases in prostate-specific antigen * lesions accessible for serial biopsy * no known brain metastases patient characteristics: age: * 18 and over performance status: * ecog 0-2 or * karnofsky 60-100% life expectancy: * more than 3 months hematopoietic: * wbc at least 3,000/mm\^3 * absolute neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 hepatic: * bilirubin normal * ast/alt no greater than 2.5 times upper limit of normal renal: * creatinine normal or * creatinine clearance at least 60 ml/min cardiovascular: * no symptomatic congestive heart failure * no unstable angina pectoris * no cardiac arrhythmia other: * no other concurrent uncontrolled illness * no ongoing or active infection * no prior allergic reactions to compounds of similar chemical or biological composition to 2-methoxyestradiol * no psychiatric illness or social situation that would preclude study compliance * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception for 1 month before, during, and for 1 month after study participation prior concurrent therapy: biologic therapy: * at least 4 weeks since prior biologic therapy chemotherapy: * at least 4 weeks since prior chemotherapy (6 weeks for mitomycin, nitrosoureas, or carboplatin) * no concurrent chemotherapy for cancer endocrine therapy: * luteinizing-hormone releasing-hormone agonist therapy must be continued for patients with prostate cancer except those with prior orchiectomy radiotherapy: * at least 4 weeks since prior radiotherapy * no concurrent radiotherapy for cancer surgery: * see endocrine therapy other: * recovered from prior therapy * no other concurrent therapy for cancer * no concurrent combination antiretroviral therapy for hiv-positive patients

Keywords: unspecified adult solid tumor, protocol specific