Faculty Bibliography

Objective: Data regarding conservative treatment of endometrial neoplasia (EN) consist of case series and nonstandardized treatments. Prospective trial design for this regimen has been fraught with incongruity. We sought to design and implement a protocol for the conservative management of EN using a consistent treatment regimen, assessment of response, and endpoints. Methods: Women with atypical endometrial hyperplasia (AEH) or grade 1 and 2 endometrioid endometrial carcinoma (EC) with gynecologic pathologist- confirmed diagnoses, no evidence of myometrial invasion or extrauterine disease on imaging, and no contraindication to megestrol acetatewho desired conservative management of EN were enrolled on this phase 2 study. Women received 160 mg of megestrol daily. After 12 weeks of treatment, office endometrial biopsy (EMB) was performed. If EMB did not reveal negative endometrium or progression, patients could continue treatment. Those with negative EMB underwent dilation and curettage (D&C) to confirm response, and endpointwas described as pathologic complete response (pCR) on D&C. Patientswithout pCR orwith progression continued onmegestrol for an additional 12 weeks, after which they were similarly reassessed. There were no dose escalations or modifications. Treatment could continue if necessary for as long as 24 months. After pCR, patients were instructed to pursue fertility or start a lower-dose progestin-based maintenance agent. Under this 1-stage design, a sample size of 30 patients achieved 80% power to detect a difference of 0.25 between the H0 of 0.4 and the H1 of 0.65 using a 2-sided Z test. Results: Among 31 patients enrolled in the study, 30 underwent protocol-defined treatment. Ages ranged from 27 to 49 years, with a median age of 37.5 years. 42% of patients were not Caucasian. Median time on study was 210 days (range, 50-768 days). To date, 13/30 (43%) experienced pCR, 3/30 (10%) a partial response, 5/30 (17%) an unconfirmed complete response, 7/30 (23%) stable disease with 3 sti!

Objective: Irinotecan and bevacizumab have single-agent activity in both platinum- sensitive and -resistant recurrent ovarian cancer. We sought to evaluate the efficacy and safety of irinotecan in combination with bevacizumab in these patients. The primary end point of the study was to estimate the progression-free survival (PFS) rate at 6 months. Secondary objectives included overall survival, observed response rate, duration of response, and toxicity. Methods: Patients with recurrent ovarian cancerwho had received any number of prior regimens were eligible. Irinotecan 250 mg/m2 (amended to 175 mg/m2 after treatment-related toxicities in the first 6 patients) and bevacizumab 15 mg/kg every 3 weeks were administered until disease progression or toxicity. Response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) every 2 cycles and by CA-125 criteria for those patients without measurable disease. Results: Thus far, 25 of the planned 35 patients have been enrolled in the study. Themedian age was 61 years (range, 45-78 years). Seven patients were platinum-sensitive and 18 patients were platinum-resistant. The median number of prior regimens was 5 (range, 1-12), with 10 patients having received prior bevacizumab-containing therapies and 9 patients prior topotecan-containing therapies. The median number of study treatments received was 6 cycles (range, 1-25 cycles); 4 patients withdrew after only 1 cycle (3 due to toxicity and 1 due to physician discretion). Of the 19 patients assessable for response at this time, 5 patients experienced partial response (PR), 11 patientsmaintained stable disease (SD), and 3 patients had progressive disease. Eleven of the patients with PR/SD were platinum-resistant. The observed clinical benefit rate (PR+SD) was 68% (95% CI: 50%, 86%) for the 25 enrolled patients (intention to treat). Durable responses were observed, with 9 patients having longer than 24 weeks of sustained response. Themedian PFS was 8.1 months, and the median overall survival was!

The decision to undergo major palliative surgery in end-stage gynecologic cancer is made when severe disease symptoms significantly hinder quality of life. Malignant bowel obstruction, unremitting pelvic pain, fistula formation, tumor necrosis, pelvic sepsis, and chronic hemorrhage are among the reasons patients undergo palliative surgeries. This review discusses and summarizes the literature on surgical management of malignant bowel obstruction and palliative pelvic exenteration in gynecologic oncology.

Background Suppression of neoangiogenesis and pegylated liposomal doxorubicin (PLD) each contribute to the management of platinum-resistant/refractory ovarian cancer. The aim of this study is to test the combination of bevacizumab and PLD in women with resistant or refractory ovarian cancer. Methods Eligibility criteria were no more than two prior treatments with platinum-containing regimens and one additional regimen, without anthracyclines. Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m(2)). The primary end point was progression-free survival (PFS) at 6 months; the secondary end points included side-effects, overall response rates (ORR) and survival (OS). Results Forty-six patients were enrolled. The average number of courses administered was 7. The median PFS was 6.6 months (range 1-24.6 months) according to Gynecologic Cancer Intergroup Committee (GCIC) criteria and 7.8 months (range 2-13.3 months) according to Response Evaluation Criteria in Solid Tumors (RECIST). The median OS was 33.2 months (range 3-37.5+ months). The ORR was 30.2% [95% confidence interval (CI) 17.2-46.1] and the clinical benefit rate (CBR) was 86.1% (95% CI 72.1-94.7). Adverse events included mucosal and dermal erosions (30% grade 3) and asymptomatic cardiac dysfunction. Additional toxic effects included hypertension, headache, renal dysfunction and proteinuria, wound healing delay, and one episode each of central nervous system (CNS) ischemia and hemolytic uremic syndrome. Conclusion PLD with bevacizumab has improved activity in recurrent ovarian cancer with increased toxicity.