Docetaxel is an antitublin agent with broad activity in solid tumors. Irinotecan is a topoisomerase I poison which has exhibited antitumor activity in colon, gastric, lung, and breast carcinomas. It is our hypothesis that the combination of docetaxel and irinotecan therapy in patients with solid tumors refractory to standard therapy or for whom there is no standard treatment. The objectives of the trial are: 1) to determine the maximum tolerated doses (MTD) of the combination of irinotecan (90 minute infusion) followed by docetaxel (60 minute infusion) administered on a 3 week schedule, 2) to describe the toxicitites of the combination of irinotecan and docetaxel given on the above schedule, 3) to evaluate the effect of irinotecan on the pharmacokinetics of docetaxel, 4) to seek preliminary evidence of therapeutic activity of the combination of docetaxel and irinotecan. The eligibility criteria are >18 years of age; cancer for which no know standard therapy is curative or definitely capable of extending life expectancy; adequate bone marrow, lepatic and renal function; life expectancy >12 weeks; <2 prior chemotherapy regimens for metastatic disease, and no CNS metastases, seizure disorders, pre-existing effusion, (peural, pericardial), ascites or peripheral edema. Patients meeting the eligibility criteria will receive irinotecan administered over 90 minutes followed by docetaxel administered over 60 minutes repeated every 3 weeks. The starting dose of irinotecan, 160 mg/m2 and docetaxel, 50 mg/m2. Doses of each agent will be escalated using alternately significant toxicity. Dose-limiting toxicity is defined as that dose in which >2/3 or >2/6 patients experienced > grade 3 nonhematologic or > grade3 hematologic toxicities according to NCI CTC. The maximally tolerated dose is one dose level below that dose which causes dose-limiting toxicity. An exploratory analysis will be undertaken to relate the pharmacokinetic parameters of this treatment and clinical or hematologic toxicity. Similarly, the surrogate endpoints for treatment effect, will be related to the clinical effects and the pharmacokinetic parameters.
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