GYNECOLOGIC MALIGNANCIES--NOVEL PHASE II AGENTS

这项建议的总体目标是进行小说的第一阶段研究 妇科恶性肿瘤患者应用药物的研究进展 总部设在纽约的多机构财团，纽约妇科 肿瘤学小组(NY GOG)。具体地说，这项提案将侧重于试验 新型维甲酸(R)+干扰素(干扰素)联合用药治疗慢性粒细胞白血病 局部晚期宫颈癌与拓扑异构酶-I的关系 难治性卵巢癌患者应用抑制物的研究 确定有效的方案并表征这些方案的毒性 养生法。NY GOG非常适合进行这样的研究，因为： 妇科肿瘤学家、内科医生之间的密切合作 肿瘤学家、放射肿瘤学家和附属实验室科学家； 宫颈癌和卵巢癌的庞大人口基数由 该财团；以及之前快速积累的记录 学习。NY GOG每年将进行2-3项第二阶段研究。纽约 Gog目前正在进行一项以实验室为基础的ALT-TRANS Il阶段试验 维甲酸联合干扰素治疗晚期宫颈癌 将作为R+干扰素和纽约的Il期研究的模型 纽约大学(NYU)目前正在进行Noble的Il阶段试验 将作为拟议模型的TOPO-L缓蚀剂的时间表 卵巢癌的试验。四个实验子项目将提供 相关信息，将有助于指导进一步 这些疗法的发展。在分项目1中，聚合酶链式反应 将使用技术来检测和分型人类乳头瘤病毒(HPV) 在接受R+干扰素治疗的患者的活检标本中。在分项目2中， 将进行药代动力学研究，以测量R和 尖锐而长期的。在分项目3中，维甲酸的mRNA水平 受体(RARpha、-β、-Gamma和RXR)和胞浆维甲酸 将在活检标本中检测结合蛋白(CRABP、L和II)。在……里面 子项目4，卵巢组织中TOPO-L的水平将通过 蛋白质印迹。这些实验室化验的结果将相互关联。 与治疗反应、反应持续时间和临床结果 患者参加这些试验的目的是为了确定 可能从这些治疗中受益的患者亚群 并指导未来养生法的发展。

The overall aims of this proposal are to conduct phase Il studies of novel agents in patients with gynecologic malignancies through a multiinsitutional consortium based in New York, the New York Gynecologic Oncology Group (NY GOG). Specifically this proposal will focus on trials of combinations of novel retinoids (R) + interferon (IFN) in patients with locally advanced or advanced cervix cancer and on topoisomerase-I inhibitors in patients with refractory ovarian carcinoma with the goal of identifying active regimens and characterizing the toxicities of these regimens. The NY GOG is well-suited to carry out such studies because of: the close collaboration between Gynecologic Oncologists, Medical Oncologists, Radiation Oncologists, and affiliated laboratory scientists; the large population base with both cervical and ovarian cancers served by this Consortium; and a previous track-record of rapid accrual to such studies. The NY GOG will carry out 2-3 phase II studies per year. The NY GOG is currently performing a laboratory-based phase Il trial of all-trans retinoic acid (RA) + IFN in patients with advanced cervix cancer which will serve as a model for the phase Il studies of R + IFN, and New York University (NYU) is currently performing phase Il trials of novel schedules of topo-l inhibitors which will be models for the proposed trials in ovarian cancer. Four laboratory subprojects will provide correlative information which will be useful in guiding the further development of these therapies. In subproject 1, polymerase chain reaction technology will be employed to detect and type human papillomavirus (HPV) in biopsy specimens from patients treated with R + IFN. In subproject 2, pharmacokinetic studies will be performed to measure levels of R both acutely and chronically. In subproject 3, levels of mRNA for retinoic acid receptors (RARalpha, -beta, -gamma, and RXR) and cytoplasmic retinoic acid binding proteins (CRABP l and II) will be measured in biopsy specimens. In subproject 4, levels of topo-l will be assayed in ovarian tissue by Western blot. The results of these laboratory assays will be correlated with response to therapy, response duration, and clinical outcome of patients entered on these trials with the goals of determining subpopulations of patients likely to benefit from treatment with these combinations and to guide development of future regimens.