TRIAL OF SURAMIN IN BREAST CANCER

虽然只有5%的乳腺癌患者存在转移性乳腺癌， 据估计，近40%的患者最终将 远距离传播。 考虑到预期的乳腺癌 1991年175，000例新发病例的发病率， 急需治疗。 雌激素和孕激素受体阳性的肿瘤可以减轻 但最终乳腺肿瘤会变成 激素不敏感且需要化疗。 化疗是积极的， 这种疾病，但反应是不完全的，通常持续不到一个月。 年 目前关于联合国系统所涉机制的概念 在适当的内分泌操作后疾病的进展表明 自主生长状态的发展，不依赖于雌激素， 可能由几种自分泌生长因子控制。 苏拉明是一个新的 一种抗肿瘤化合物，其化学上代表一种高电荷阴离子 由于萘上存在磺酸基团， 环. 在各种可能的机制中，已知这种药物抑制 各种生长因子如PDGF、bFGF、TGF-α和 β的 苏拉明已被证明对前列腺癌有活性， 在UMCC进行的研究使用了独特的 程序. 为了扩展这一观察，目前的提案计划测试 这种药物在乳腺癌的II期试验中靶向药物血浆， 浓度为150-250微克/毫升，这是我们发现的活性水平。 前列腺癌的I期研究，毒性可接受。 符合条件的妇女 必须有可测量的疾病，并且如果ER或PR 肯定的：第 他们可能只接受了一种化疗方案， 转移性疾病 我们将进一步扩大对 适应性舒拉明的药代动力学和药效学行为 通过反馈进行控制，并仔细监测该药剂的毒性 在这个新的病人群体中。 将对15名患者进行初始队列研究， 如果缓解，则进行评价，目的是治疗总计25例患者。 观察

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.