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Purpose To determine the efficacy and side effects of taxanes, with or without platinum, for the treatment of sex cord-stromal tumors of the ovary. Patients and Methods We conducted a retrospective review of all patients seen from 1985 to 2002 at The University of Texas M.D. Anderson Cancer Center with ovarian sex cord-stromal tumors. Eligible patients underwent pathology confirmation and clinical evaluation at M.D. Anderson and received a taxane for initial or recurrent disease. Results Of 222 patients identified, 44 were eligible for analysis. For nine patients treated in the first-line adjuvant setting, median progression-free survival (PFS) was not reached at 51 months. Of two patients treated for measurable disease in the first-line setting, one had a complete response. Median PFS was 34.3 months; median overall survival (OS) was not reached. Median follow-up was 90.3 months (range, 39.4 to 140.5 months). Response rate for 30 patients treated with a taxane ± platinum for recurrent, measurable disease was 42%. Median PFS was 19.6 months; median OS was not reached. Median follow-up was 100.7 months (range, 8.1 to 361.3 months). The presence of platinum correlated with response in the recurrent, measurable disease setting. The number of patients was insufficient to detect relative efficacy of paclitaxel and docetaxel. Adverse effects of paclitaxel included neutropenia (n = 6), anemia (n = 1), thrombocytopenia (n = 1), myelodysplasia (n = 1), and hypersensitivity (n = 1). Conclusion Taxanes seem to be active agents in the treatment of patients with sex cord-stromal tumors of the ovary. The combination of taxanes with platinum in the treatment of this disease deserves additional investigation.

Purpose Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer characterized by early metastasis, resistance to therapy, and a high mortality rate. Little is known about the biology of these tumors. Smaller studies suggest that Her-2/neu may be involved in the tumorigenesis of this disease. The purpose of this study was to evaluate the protein expression and gene amplification of Her-2/neu in UPSC and to determine its prognostic value. Patients and Methods Tumor tissue from 68 patients with UPSC treated at The University of Texas M.D. Anderson Cancer Center from 1989 to 2002 was available. Her-2/neu expression was evaluated by immunohistochemistry (IHC). Overexpression was defined as complete membrane staining in greater than 10% of the cells. In tumors with overexpression of Her-2/neu by IHC, fluorescence in situ hybridization (FISH) was performed to assess gene amplification. Clinical and pathologic information was obtained from medical records. Results Twelve (18%) of 68 tumors demonstrated Her-2/neu overexpression. Of these, only two showed gene amplification. When evaluating all 68 patients, Her-2/neu overexpression was associated with a poorer overall survival (OS; P = .008). In our multivariate Cox proportional hazards models, Her-2/neu IHC overexpression, lymph node status, and stage were each associated with OS (P ≤ .05). Conclusion Positive IHC overexpression of Her-2/neu was seen in 18% of UPSCs but was rarely correlated with Her-2/neu gene amplification. Overexpression of Her-2/neu was associated with a worse overall prognosis. The use of trastuzumab (Herceptin; Genentech, South San Francisco, CA) in women with UPSC should be further evaluated in a clinical trial setting.

PURPOSE To investigate and define better the role of salvage surgery for patients with chemorefractory gestational trophoblastic disease (GTD). PATIENTS AND METHODS A retrospective review of medical records at The University of Texas M.D. Anderson Cancer Center identified 33 patients with chemorefractory GTD who underwent salvage surgery between 1962 and 1991. The end points selected for analysis were serologic response and survival. RESULTS Initial salvage procedures consisted of 29 hysterectomies, four thoracotomies, and one nephrectomy (in conjunction with a hysterectomy). Fourteen patients (42%) had a serologic complete response (CR) to surgery (normalization of human chorionic gonadotropin [hCG]), 10 (30%) had a partial response (> 50% decrease in hCG level), and nine had no response (< or = 50% decrease in hCG level). Of 19 patients who received further chemotherapy, eight (42%) attained a CR. Four patients underwent a second salvage surgery: two thoracotomies, one craniotomy, and one partial hepatectomy. All achieved a CR. The probability of achieving a CR was influenced by the time from diagnosis to surgery, number of preoperative disease sites, preoperative World Health Organization (WHO) score, and histologic type. Survival was influenced by the type of antecedent pregnancy, number of preoperative regimens, number of preoperative disease sites, time from diagnosis to surgery, and preoperative WHO score. CONCLUSION Based on the findings of this study, it appears that a select subset of patients with chemorefractory GTD who have a limited number of clinically detectable tumor foci may benefit from salvage surgery.

9539 Background: Quality performance measures for cancer care, including use of chemotherapy in the last two-weeks of life, will be required for reporting. In this study, we evaluated the pattern and frequency of chemotherapy use for ST patients in the last two-weeks of life, and whether such treatment included standard or investigational drugs. Methods: We conducted a retrospective study of 5,607 adult cancer patients (≥18 years) who received their care at The University of Texas MD Anderson Cancer Center and died between December 01, 2010 through May 31, 2012. Data on patients’ demographics, and chemotherapy agents dispensed (excluded: hormones) were obtained from the institution’s administrative databases. Type of treatment (research versus standard) was obtained from our chemotherapy dispensed database. Chi-square test and Fisher's exact test were used to determine the association between categorical variables.All statistically significant levels were determined with P values < 0.05. Results: Only 3.9% (216/5,607) of ST patients who died had received chemotherapy within 14 days EOL. For those 216 patients who received chemothapy: median age 64 years; 48% female; 89% metastatic disease. The distribution by chemotherapy treatment route: intravenous (IV) 85%; IV plus oral 6%; oral 6%; other 3%. The distribution of patients by number of chemotherapy agents: one 56%; two 31%, and three or more 13%. Among those who received chemotherapy, 98.6% (213/216) of the chemotherapy administered were standard agents. There were no differences in frequency distribution for chemotherapy treatment route (p>0.05), number of chemotherapy agents (p>0.05) between patients with metastatic and non-metastatic disease, or between men and women (p>0.05). Conclusions: Our results indicate EOL chemotherapy use was infrequent in our patients with STs, and most of those treated received standard chemotherapy, with simple one or two drug regimens. We need more research to determine factors that influence chemotherapy use at EOL, and if it palliates physical symptoms and/or emotional distress in advanced stages of disease.

9538 Background: Oncologists will be required to report quality measures for cancer care, including use of chemotherapy in the last two-weeks of life. In this study, we evaluated how use of chemotherapy in ST patients (pts) within 14 days of EOL may be influenced by clinical factors. Methods: Adult pts (≥18 years) treated for ST at our institution, deceased December 01, 2010 through May 31, 2012, were retrospectively studied. Data on demographics, chemotherapy (excluded: hormones) within 14 days EOL, comorbidities, and cancer diagnoses were from tumor registry and administrative databases. Logistic regression analysis was performed for association of EOL chemotherapy with age, gender, ethnicity, comorbidities , cancer types, and metastatic status. Results: 5,607 pts met study criteria: median age 64 years; 48% female; 76% metastatic disease. EOL chemotherapy frequency was 3.9% overall, 4.6% in metastatic disease versus 1.7% in non-metastatic disease (p

e16574 Background: Metastatic solid tumors (MST) are rarely curable. However, treatment options for MST (stage IV) are increasing. Thus, discussing realistic therapeutic goals is critical to planning appropriate end of life medical interventions. We analyzed chemotherapy use within 30 days prior to end of life, and DNR orders, among patients with solid tumors (ST) who died at our institution. Methods: We reviewed all adult patients (age>18 years) with a diagnosis of ST who died in hospital at M.D. Anderson Cancer Center from June, 2010 through March, 2011 (excluded: hematologic malignancies). Data on patients’ demographics, chemotherapy within last 30 days (excluded: hormones), inpatient DNR orders, and comorbidities were from the institution’s administrative databases. Statistical analyses were: chi-square test for association between variables; univariate and logistic regression for association of chemotherapy use with age, gender, ethnicity, comorbidities, years of disease diagnosis, and metastatic status; statistical significance is defined as P value < 0.05. Results: 357 ST patients died in hospital: median age 60 years; 41% female; 81% MST; 44% had lung, breast or colorectal cancer. Patients receiving chemotherapy within last 30 days of life: 29% with MST; 18% without metastases (p = 0.06). DNR orders: 90% with MST, versus 79% without metastases (p =0.01). By regression analyses, there were no significant factors for chemotherapy use during the last 30 days of life (age, gender, ethnicity, years from time of disease diagnosis, metastatic status, and co-morbid conditions, each p>0.05). Conclusions: Only a small portion of patients with MST received chemotherapy within the last 30 days of life, while most had DNR orders indicating an end of life discussion. We need to study further the relationship of early discussion of treatment goals to clinical outcomes and end of life planning.

5016 Background: Everolimus is an oral rapamycin analog that selectively inhibits mTOR. PTEN mutations occur in 40-60% of endometrial cancer (EC). Although PTEN loss leads to constitutive activation of AKT and up-regulation of mTOR, it is not clear which EC patients will benefit from this targeted therapy. PS6K is a downstream marker of mTOR activation. Prior studies suggest KRAS mutations are associated with resistance to everolimus. We evaluated primary tumor specimens to determine if expression of biomarkers in the mTOR pathway or KRAS mutations would predict response to therapy. Methods: Correlative studies evaluating PTEN and PS6K expression by immunohistochemistry (IHC) and KRAS mutational analysis were performed from tissue blocks of primary tumor. Response to therapy was estimated with Fisher’s exact test. Positive predictive value (PPV) for each variable was calculated. Tumor from patients enrolled in a single institution, open-labeled, single arm, Phase II study in pretreated patients with recur...

5502 Background: The finding of PTEN mutations in 40–60% of EC suggests this pathway is important in the pathogenesis of this disease. Loss of PTEN leads to constitutive activation of AKT, which le...

16025 Background: Uterine serous carcinoma (USC) is a rare, aggressive uterine tumor biologically distinct from typical endometrial cancers. Imatinib mesylate (IM)-associated kinases (kit, abl, PDGFR-B) are overexpressed and activated in most tumors from patients (pts) with USC. Single agent paclitaxel (TAX) has a good response rate but short duration of response in pts with USC. The purpose of this study was to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of escalated doses of IM with a fixed dose of TAX. Methods: Pts with newly diagnosed (stage IIIC/IV) or recurrent USC were eligible (pts were required to have tumors that expressed at least one of the IM-targeted kinases by immunohistochemistry). Measurable disease was not required. TAX was administered at 175 mg/m2 every three weeks. One dose reduction to 135 mg/m2 was allowed. IM was given daily (400 mg, 500 mg or 600 mg). A 3+3 design was implemented. Pts with measurable disease were treated until progression or treatment associated toxicity. Pts with no measurable disease were treated for six cycles. Results: 11 pts were enrolled. The median age was 62 years (47–79). A total of 50 cycles were administered. Three pts were treated at the first dose level (400 mg), 6 pts treated at the second dose level (500 mg), and 2 pts were treated at the highest dose level (600 mg). Three DLTs were observed (1 at 500 mg level and 2 at 600 mg level) including: rash, neutropenia, and fatigue. IM 500 mg daily and TAX 175 mg/m2 every three weeks was the MTD. There were 3 serious adverse events not related to treatment (infection, dyspnea, pain). Neutropenia was the most common grade 3 or 4 toxicity but only one patient required TAX dose reduction. 8 pts were evaluated for efficacy (2 with measurable disease, 6 with no measurable disease). 1 (of 2) pts with measurable disease had a partial response and was treated for 13 cycles. Of the 6 pts with no measurable disease, 2 recurred (5 and 10 months). The median disease free interval for the pts without recurrent disease was 22 months (6–30). Conclusion: Combination therapy of IM and TAX is well tolerated with minimal side effects in pts with advanced or recurrent USC. Initiation of the phase II component of this study is warranted to better evaluate efficacy. No significant financial relationships to disclose.

5589 Background: Systemic therapy for advanced malignant mixed müllerian tumor of the uterus (MMMT) after surgery has been disappointing. Currently, the most common treatment regimen is ifosfamide and platinum. Moderate success has been documented using paclitaxel in MMMT of the ovary. The purpose of this study is to evaluate carboplatin and paclitaxel in patients with advanced (IIIb-IVb) and recurrent MMMT of the uterus. Methods: A single arm, prospective, non-randomized phase II trial opened in October 2001. The planned sample size is 37 evaluable patients, with time to progression and response rate as the primary endpoints. Patients receive carboplatin (AUC 5) and paclitaxel (175 mg/m2) every 21 days. Patients treated adjuvantly receive a total of 6 cycles or until progression or toxicity. Patients with disease present at study entry are treated until progression or toxicity. Results: To date, 18 patients have been enrolled. Seven patients received adjuvant treatment and 11 patients had documented disease at study entry. In the adjuvant group, the median progression-free interval was 15.8 months and median overall survival from treatment initiation was 20.2 months. Four of these 7 patients (57%) continue to be followed with a median follow-up of 19.2 months. In the patients with documented disease, the median progression- free interval was 7.8 months and the median overall survival from treatment initiation was 12.4 months. In this group, there were 3 complete and 4 partial responses (63.6% response rate). Over 45% of patients with disease at study entry are alive with a median follow-up of 14.0 months. Four patients experienced grade 4 granulocytopenia. Only two (11%) had treatment-limiting toxicity, one with grade 3 neuropathy and one with grade 3 fatigue. Conclusions: Carboplatin and paclitaxel appear to have improved tolerability and response rate (63.6%) compared to previous reports of ifosfamide and cisplatin (33% RR) in treating MMMT of the uterus. This regimen seems extremely promising and we are awaiting the final results of this trial. No significant financial relationships to disclose.

5081 Purpose Clear cell carcinoma of the endometrium (CCC) and uterine papillary serous carcinoma (UPSC) are uncommon and collectively account for 10% of epithelial endometrial cancers. However, gr...