Smith, Judith A.

5595 Background: Endometrial cancer is the most common cancer of the female genital tract. It affected 41,200 women in the year 2006 and caused 7,350 deaths. Therapy options for recurrent/advanced endometrial cancer are limited. Treatment with radiation and chemotherapy has shown only limited success. Methods: In a phase II IRB approved trial, Mifepristone was given to patients with progesterone receptor positive advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma at a dose of 200mg/day orally. Patients were evaluated every 4 weeks to assess treatment-related toxicities and response. Imaging was obtained initially at 8 weeks then every 12 weeks for evaluation of response. Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to assess toxicity. Results: Twelve of 13 enrolled patients were evaluable for response in the first phase of accrual. Stable disease was noted in 3/12 (16, 20, and 44+ weeks). Two were endometrioid endometrial cancer and one with LGESS. No complete responses were seen, one patient remains in treatment. The most frequently reported grade 1–2 tumor related toxicities were anorexia, mood alterations, and fatigue (55%). Twenty-seven percent had asymptomatic elevations of ACTH. The most common Grade 3 toxicities were fatigue and dyspnea (27% and 18%). Only one patient experienced a Grade 4 dyspnea. No serious treatment-related adverse events occurred. Conclusions: Single agent mifepristone in patients with recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma showed no complete responses. Stable disease was reported 25%, one patient remains stable at 44 weeks. Recent reports suggests that mifepristone may also work via non hormonal targets while single agent mifepristone has minimal activity in this setting. Further evaluation in combination therapy in endometrial cancer should be considered. No significant financial relationships to disclose.

Bone marrow is a complex organ responsible for the regulation of hematopoietic cell distribution throughout the human body. Patients receiving antineoplastic agents as a therapeutic intervention for hematologic malignancy often experience varying degrees of myelotoxicity. Antineoplastic agents cause hypocellularity in marrow resulting in a reduction in hematopoietic tissue activity and a corresponding decline in cell production. Quantifying the adverse effects on hematopoiesis is based on the properties of a single agent, the use of individual drugs within a combination chemotherapy regimen, and the course, or courses, of chemotherapy designed to treat cancer. The direct or indirect suppression of erythrocytes, granulocytes, and megakaryocytes has potential for multiple negative clinical consequences ranging from increased monitoring of blood counts to life-threatening infection and death. This review will provide an overview of the structure and function of competent adult bone marrow, describe the process of hematopoiesis, and characterize the myelotoxicities associated with common antineoplastic agents currently used in the treatment of cancer.