combination chemotherapy in treating children with solid tumors that have not responded to previous therapy

Conditions: Unspecified Childhood 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. combining more than one drug may kill more tumor cells. purpose: phase i trial to study the effectiveness of vincristine plus irinotecan in treating children who have solid tumors that have not responded to previous therapy.

objectives: * determine the maximum tolerated dose and dose limiting toxicity of vincristine when administered in combination with irinotecan in children with refractory solid tumors. * determine the safe and tolerable phase ii dose of this combination regimen in this patient population. * determine the pharmacokinetics of this combination regimen in these patients. * determine the incidence and severity of other toxicities of this combination regimen in these patients. * determine preliminary evidence of antitumor activity of this combination regimen in this patient population. outline: this is a dose-escalation study of vincristine. patients receive vincristine iv on day 2 of the first course (day 1 of subsequent courses) and days 8, 15, 22, and 29, and irinotecan iv over 1 hour on days 1-5 and 22-26. courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. patients with responsive or stable disease receive additional courses of therapy for a maximum of 1 year. cohorts of 3-6 patients receive escalating doses of vincristine until the maximum tolerated dose (mtd) is reached. 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. patients are followed every 6 months for 4 years and then annually thereafter. projected accrual: a total of 3-12 patients will be accrued for this study within 1 year.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed initial diagnosis of malignant solid tumor refractory to conventional therapy or for which no effective therapy exists * brain tumors allowed if not on anticonvulsants * brainstem gliomas allowed without histologic diagnosis * solid lymphomas allowed * no bone marrow involvement patient characteristics: age: * 1 to 21 performance status: * karnofsky 50-100% if over 10 years of age * lansky 50-100% if 10 years of age and under life expectancy: * at least 8 weeks hematopoietic: * absolute neutrophil count at least 1,000/mm\^3 * platelet count at least 100,000/mm\^3 * hemoglobin at least 8 g/dl (transfusion allowed) hepatic: * bilirubin no greater than 1.5 mg/dl * alt less than 5 times normal * albumin at least 2 g/dl renal: * creatinine normal for age or * glomerular filtration rate normal for age other: * no uncontrolled infection * no other significant systemic illness * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * at least 1 week since prior biologic therapy and recovered * at least 1 week since prior growth factors * no prior stem cell transplantation chemotherapy: * at least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered * no more than 2 prior chemotherapy regimens * no other concurrent cancer chemotherapy endocrine therapy: * concurrent dexamethasone allowed in patients with cns tumors provided dose is stable or decreasing for at least 2 weeks prior to study radiotherapy: * recovered from prior radiotherapy * at least 2 weeks since prior local palliative radiotherapy (small port) * no prior substantial bone marrow radiotherapy * no prior central axis radiotherapy * no concurrent radiotherapy surgery: * not specified other: * no concurrent anticonvulsants * no other concurrent anticancer therapy or investigational agents

Keywords: unspecified childhood solid tumor, protocol specific