TRIAL OF SURAMIN IN BREAST CANCER

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Although only 5% of women with breast cancer present with metastatic disease, it is estimated that nearly 40% of all patients will eventually manifest distant dissemination. Given an anticipated breast cancer incidence of 175,000 new cases in 1991, improvements in metastatic treatment are urgently needed. Estrogen and progesterone receptor positive tumors can be palliated effectively by hormonal treatments but eventually breast tumors become hormone insensitive and require chemotherapy. Chemotherapy is active in this disease but responses are incomplete and generally last less than one year. Current concepts regarding the mechanisms involved in the progression of disease following appropriate endocrine maneuvers suggest the development of an autonomous growth status, independent of estrogen, possibly controlled by several autocrine growth factors. Suramin is a new antitumor compound which chemically represents a highly charged anionic polymer due to the presence of sulfonic acid groups on too naphthalene rings. Among various possible mechanisms, this drug is known to suppress the action of various growth factors such as PDGF, bFGF, TGF-alpha and beta. Suramin has been shown to have activity in prostate cancer in studies conducted at the UMCC using a unique pharmacologically guided program. To extend this observation, the current proposal plans to test this drug in a phase II trial in breast cancer targeting a drug plasma concentration of 150-250 micro-g/ml, a level found to be active in our phase I study in prostate cancer with acceptable toxicity. Eligible women must have measurable disease and must be hormone refractory if ER or PR positive. They may have received no more than one chemotherapy regimen for metastatic disease. We will further extend our study of the pharmacokinetic and pharmacodynamic behavior of Suramin using adaptive control with feedback and carefully monitoring the toxicities of this agent in this new patient population. An initial cohort of 15 patients will be evaluated with the intent to treat a total of 25 patients if responses are observed.