Suramin is a unique polyanionic compound which blocks a variety of growth factors involved in the proliferation of human tumors. Doxorubicin is an anthracycline antibiotic which interferes with DNA topoisomerase II. Based on preclinical data, suramin with sequential doxorubicin possess cytotoxic synergy in a number of tumor types including prostate and breast carcinomas. It is our hypothesis that suramin with sequential doxorubicin is a potent and effective antitumor treatment. We are undertaking a phase I trial of suramin with sequential doxorubicin 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 MTD of 4 days of short infusion suramin followed by 1 dose of ADR (varying doses) repeated every 4 weeks, 2) to describe the toxicities of suramin with sequential ADR given on this schedule, 3) to assess the development of peripheral neuropathy in patients treated with suramin-ADR on this schedule, 4) to seek preliminary evidence of the antitumor effect of suramin with sequential ADR, 5) to determine the effect of suramin on total and free IGF-1, IGF-2, and IGFBPs, 6) the pharmacokinetic studies will be performed to explore relationships between pharmacokinetic parameters and potential neurotoxicity. Those parameters will include total dose, peak and trough concentrations, total AUC and time above a threshold concentration or AUC. The eligibility criteria are >18 years of age; unavailability of another more conventional form of therapy which offers a reasonable chance to cure, performance status 0-2, adequate organ function, life expectancy of >12 weeks, < prior chemotherapy regimens for metastatic disease and absence of peripheral neuropathy > grade 2. Patients meeting the eligibility criteria will receive suramin intravenously on days 1-4 followed by a bolus infusion of doxorubicin done on day 5. Treatment will be repeated every 28 days up to a maximum of 3 cycles. The starting dose of doxorubicin will be 20 mg/m2 on day 5 and will be escalated to 30, 45, and 60 mg/m2 in subsequent patient cohorts. The dose of suramin will be fixed, and is chosen to yield peak and through levels of 200 ug/ml and 150 ug/ml respectively. Dose-limiting toxicity is defined as that dose in which >2/3 or >2/6 patients experienced serum creatinine >2 times baseline or > 2 times institutional upper normal (whichever is highest) >grade 3 other nonhematologic or >grade 3 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.
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