irinotecan and gemcitabine in treating patients with refractory 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. combining more than one drug may kill more tumor cells. purpose: phase i trial to study the effectiveness of combining irinotecan with gemcitabine in treating patients who have refractory advanced solid tumors.

objectives: * determine the maximum tolerated dose of irinotecan when administered with gemcitabine in patients with refractory advanced solid tumors. * determine the antitumor activity and toxicity of this regimen in these patients. * determine the pharmacokinetics and pharmacodynamics of this regimen in these patients. * determine the optimal dose and time interval for this regimen in these patients. outline: this is an open-label, non-randomized, dose-escalation study of irinotecan. patients receive irinotecan iv over 90 minutes on days 1 and 8 and gemcitabine iv over 30 minutes on days 2 and 9. courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. patients are followed every 8 weeks. projected accrual: a total of 24 patients will be accrued for this study within 2 years.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed advanced solid tumor that is refractory to prior treatment * considered incurable with other modalities * measurable or evaluable disease * the following are not considered measurable or evaluable: * bone metastases * pleural, pericardial, or peritoneal effusions * irradiated lesions (unless progression is documented after radiotherapy) * metastatic disease that has been followed using serum tumor markers allowed * no symptomatic brain metastases * brain metastases may not be sole site of metastatic disease patient characteristics: age * 18 and over performance status * ecog 0-1 life expectancy * at least 12 weeks 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 * ast and alt no greater than 1.5 times normal * bilirubin no greater than 1.5 mg/dl * no clinically apparent jaundice renal * creatinine no greater than 1.6 mg/dl or * creatinine clearance at least 50 ml/min cardiovascular * cardiac function normal * no uncontrolled heart disease * no myocardial infarction within the past 3 months * no congestive heart failure * no unstable or uncontrolled angina other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * no active infection requiring systemic therapy * no uncontrolled seizures * no uncontrolled diabetes mellitus prior concurrent therapy: biologic therapy * not specified chemotherapy * no prior gemcitabine * no prior camptothecin compounds * prior irinotecan allowed * no other concurrent chemotherapy endocrine therapy * not specified radiotherapy * see disease characteristics * at least 14 days since prior radiotherapy * no concurrent radiotherapy surgery * not specified other * more than 30 days since prior clinical trial participation * no other concurrent investigational medications

Keywords: unspecified adult solid tumor, protocol specific