temozolomide plus peg-interferon alfa-2b in treating patients with advanced solid tumors

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. peg-interferon alfa-2b may interfere with the growth of cancer cells. combining temozolomide with peg-interferon alfa-2b may be an effective treatment for advanced solid tumors. purpose: phase i trial to study the effectiveness of combining temozolomide and peg-interferon alfa-2b in treating patients who have advanced solid tumors.

objectives: * determine the safety and tolerability of temozolomide and peg-interferon alfa-2b in patients with advanced refractory solid tumors or chemotherapy-naive advanced cancer. * determine the maximum tolerated dose (mtd) and dose-limiting toxicity of this regimen in this patient population. * determine the pharmacokinetics of peg-interferon alfa-2b at the mtd when administered with temozolomide in this patient population. * determine the anti-tumor activity of this regimen in these patients. outline: this is a dose-escalation study. patients receive oral temozolomide on days 1-7 and 15-21 and peg-interferon alfa-2b subcutaneously on days 1, 8, 15, and 22. treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cohorts of 1-9 patients receive escalating doses of temozolomide and peg-interferon alfa-2b 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 6 patients experience dose-limiting toxicity. projected accrual: a maximum of 24 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed advanced solid tumor that is refractory to standard therapy or * histologically confirmed chemotherapy-naive advanced cancer for which no curative therapy or higher priority palliative chemotherapy exists * brain metastasis allowed * no bone marrow involvement of tumor patient characteristics: age: * 18 and over performance status: * ecog 0-2 life expectancy: * not specified hematopoietic: * absolute neutrophil count greater than 1,500/mm\^3 and/or * platelet count greater than 100,000/mm\^3 hepatic: * alt or ast less than 3 times upper limit of normal (uln) (5 times uln if liver metastases present) * no autoimmune hepatitis renal: * creatinine less than 2.5 times uln cardiovascular: * no severe coronary artery disease * no congestive heart failure pulmonary: * no severe chronic obstructive pulmonary disease gastrointestinal: * no frequent vomiting * no medical condition that would interfere with oral medication intake (e.g., partial bowel obstruction, partial intestinal bypass, or external biliary diversion) other: * no other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * no known or suspected hypersensitivity to imidazotetrazin, interferon alfa, or any excipient or vehicle included in the formulation or delivery system of study drug * no history of autoimmune disease * no preexisting severe psychiatric condition or history of severe psychiatric disorder (including suicidal ideation or attempt) * no life-threatening condition or severe preexisting condition * no uncontrolled thyroid abnormalities * no nonmalignant systemic disease * no active uncontrolled infection * hiv negative * no aids-related illness * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * at least 3 weeks since prior biologic agents (e.g., bi-specific antibodies, interleukin-2, or interferon) and recovered (excluding alopecia) * no prior allogeneic, syngeneic, or autologous bone marrow or stem cell transplantation * no other concurrent biologic therapy * no concurrent colony stimulating factors or epoetin alfa for the prevention of myelotoxicity chemotherapy: * see disease characteristics * at least 4 weeks since prior chemotherapy (more than 6 weeks for nitrosoureas, melphalan, or mitomycin) and recovered (excluding alopecia) * no prior high-dose chemotherapy and stem cell transplantation * no more than 3 prior chemotherapy regimens * no other concurrent chemotherapy endocrine therapy: * not specified radiotherapy: * at least 6 weeks since prior wide-field radiotherapy to at least 25% of bone marrow (e.g., pelvic radiotherapy) * more than 6 weeks since prior strontium chloride sr 89 or samarium sm 153 lexidronam pentasodium * recovered from prior radiotherapy (excluding alopecia) * no concurrent radiotherapy surgery: * at least 4 weeks since prior major surgery * at least 1 week since prior minor surgery other: * at least 4 weeks since prior investigational therapy

Keywords: unspecified adult solid tumor, protocol specific