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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endometrial cancer is a highly curable malignancy when it presents as uterine-confined disease, but the prognosis for metastatic or recurrent endometrial cancer is poor. The median survival of women enrolled in trials for recurrent or metastatic endometrial cancer is only approximately 12 months. Hormonal therapy, most commonly with progestins, benefits a small group of patients. Cytotoxic chemotherapy is indicated as frontline treatment for the majority of women with metastatic or recurrent disease. Anthracyclines, platinum compounds, and taxanes consistently achieve response rates greater than 20% in single-agent trials of chemotherapy-naive patients. Combination chemotherapy typically produces higher response rates, although combination regimens have not always improved survival historically. Doxorubicin plus cisplatin has been accepted as the Gynecologic Oncology Group (GOG) standard regimen based on phase III data. Recently, a COG randomized trial compared doxorubicin plus cisplatin to the triplet of doxorubicin, cisplatin, and paclitaxel, and it was found that the addition of paclitaxel significantly improved response rate, progression-free survival, and overall survival. Moreover, chemotherapy has been reported to improve survival when
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PMID:Chemotherapy in endometrial cancer. 1698 69

Endometrial cancer is one of the most common gynecologic malignancies. In patients with advanced or recurrent endometrial cancer survival is greatly diminished. Hormonal therapy and chemotherapy play a major role in the management of advanced or recurrent endometrial cancer. Endocrine therapy provides a 10-20% response rate (RR) and survival of less than 1 year. Combination chemotherapy offers a RR of 40-60%, but the survival is still less than 1 year. The combination of cisplatin plus doxorubicin is the most commonly used regimen, but carboplatin plus paclitaxel represents an efficacious, low toxicity regimen in advanced or recurrent endometrial cancer. The addition of paclitaxel to cisplatin plus doxorubicin appears to improve response rates, progression-free survival and overall survival, but to worsen toxicity profile. At this time the focus of future research should be on the use of novel targeted agents, since it is unlikely that further significant advances could be made with chemotherapy and endocrine therapy. mTOR inhibitors represent a promising therapeutic strategy for endometrial cancer. Anti-HER-2/neu targeted therapy might be a novel and attractive therapeutic option in patients with biologically aggressive variants (uterine serous papillary carcinoma, clear cell carcinoma) of endometrial cancer. Research in better understanding the signal transduction pathways in endometrial carcinogenesis will allow the development of specific and selective molecularly targeted inhibitors.
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PMID:Systemic therapy in metastatic or recurrent endometrial cancer. 1719 49

The aim of this study was to assess the efficacy and tolerability of paclitaxel and carboplatin (TC) in the treatment of patients with advanced or recurrent endometrial cancer. Patients eligible for this retrospective analysis had endometrial cancer with either advanced or recurrent measurable disease (untreated primary stage III/IV or stage III/IV patients with persistent, measurable disease [> or =2 cm] after surgery), Eastern Cooperative Oncology Group (ECOG) performance status > or =3, and received at least one cycle of TC. Response rates were determined using Response Evaluation Criteria in Solid Tumors criteria. Institutional Review Board approval was obtained prior to the initiation of this study. Eighty-five eligible patients, with a median age of 62 years (range 36-80) were identified. Fifty-seven (67%) of patients were treated at the time of recurrence. Prior radiation therapy had been used in the treatment of 36 (42%) patients, while 13 (15%) patients had received prior chemotherapy. Median follow-up time was 11.7 months (range 1.1-96.7 months), and the median number of cycles of therapy received was six (range 1-18). The overall response rate (ORR) was 43%, with a complete response rate of 5% and a partial response rate of 38%. Chemotherapy-naive patients had an ORR of 47%. Only seven (8%) patients had to discontinue therapy due to toxicity. Median progression-free survival was 5.3 months (95% CI, 4.6-7.4), with a median overall survival of 13.2 months (95% CI, 11.7-18.2). We conclude that TC is an active and tolerable regimen in the treatment of patients with advanced or recurrent endometrial cancer.
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PMID:Paclitaxel and carboplatin in the treatment of advanced or recurrent endometrial cancer: a large retrospective study. 1729 Dec 53

Our experience with hyperthermic intraperitoneal chemotherapy (IPHC) in conjunction with surgical resection for endometrial cancer recurrent within the abdominal cavity was reviewed. Eligible patients underwent exploratory laparotomy with the aim of resecting disease to < or =5 mm maximum dimension followed immediately by intraperitoneal perfusion of cisplatin (100 mg/m(2)) heated to 41-43 degrees C (105.8-109.4 degrees F) for 1.5 h. Data for analysis was extracted from retrospective chart review. Five patients underwent surgery and IPHC between September 2002 and January 2005 for abdomino-pelvic recurrence. Original stage and histology were 1A papillary serous (1), 1C endometrioid with clear cell features (1), and 1B endometrioid (3). Mean age was 61 (41-75) years, mean prior laparotomies were 1.4 (1-2), and mean chemotherapy agent exposure was 1.6 (0-4). Mean time from initial treatment to surgery and IPHC was 47 (29-66) months. Mean length of surgery was 9.8 (7-11) h after which three patients had no residual disease and two had < or =5 mm disease. The mean duration of hospital stay was 12.6 (6-20) days. Postoperative surgical complications included wound infection with septicemia in one patient. Mean maximum postoperative serum creatinine was 1.02 (0.6-1.70) mg/dL. There was no ototoxicity or neuropathy and no perioperative mortality. No patients have been lost to follow-up. Two are living disease free at 28 and 32 m and two are living with disease at 12 and 36 m. One patient died at 3 m without evidence of cancer. Two patients who had no residual macroscopic disease at the end of surgery are alive at 32 and 36 m. The combination of IPHC with surgery for recurrent endometrial carcinoma is relatively well tolerated. The unexpectedly long survival seen in this cohort supports a phase II trial of IPHC with cisplatin for recurrent endometrial cancer.
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PMID:Cytoreduction and intraperitoneal heated chemotherapy for the treatment of endometrial carcinoma recurrent within the peritoneal cavity. 1729 Dec 54

There is no generally accepted standard chemotherapy in treatment of advanced and recurrent endometrial carcinoma. Cisplatin and doxorubicin with or without cyclophosphamide are widely used. Response rates have improved with combination chemotherapy compared with single-agent therapy. A platinum analog seems to be an important part of the chemotherapy regimen. Since few patients are cured from their disease and since the duration of response is short, further improvement of this therapy is warranted. During the past years, the taxanes (paclitaxel) are being added to prior evaluated regimens and not only improved response rates are reported but also increased toxicity is observed. In a prospective, phase II, multicenter study, carboplatin (area under the curve = 5) and paclitaxel (175 mg/m(2)) were evaluated in treatment of primary advanced and recurrent endometrial carcinoma. In total, 66 patients were recruited during the years 2000-2004. Eighteen primary advanced tumors and 48 recurrences were treated. All histologic types and tumor grades were allowed. The median follow-up was 57 months (range 37-69 months). The overall response rate was 67% (95% CI 55-78). The complete response rate was 29% and the partial response rate 38%. Primary advanced and recurrent tumors as well as endometrioid and nonendometrioid tumors showed similar response rates. The median response duration was 14 months. The 1- and 3-year survival rates were 82% and 33%, respectively. The main toxicities were hematologic and neurologic (sensory neuropathy). The response rates were encouraging, superior to prior platinum-containing regimens, but response duration and the long-term survival rate were still short. The neurologic toxicity was frequent and was a substantial problem in this series of patients. Further research is highly needed to improve the treatment of advanced and recurrent endometrial cancer.
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PMID:Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up. 1794 17

Endometrial carcinoma is the most common and potentially curable gynecologic malignant neoplasm. The staging of endometrial cancer, according to the International Federation of Gynecology and Obstetrics (FIGO), is surgical. Recent studies suggest a therapeutic benefit associated with extensive retroperitoneal lymph node evaluation to determine the disease extent and thereby more effectively direct potentially life-saving adjuvant therapy. Due to the increasing number of endometrial cancer patients who undergo surgical staging, some independent prognostic factors have been identified in early stages (stage I-II), including lymph-vascular space involvement, histologic grade 3, aggressive histologic subtypes (uterine papillary serous carcinoma, clear cell carcinoma), depth of myometrial invasion, cervical invasion and the age of patients. Adjuvant radiation therapy, known to offer survival benefit in advanced-stage disease, may also offer survival benefit in intermediate-risk surgical stage I, but this is followed by a significant risk of serious complications. Based on randomized clinical trials, this review identified that only a limited body of evidence is available which can help clinicians make decisions about adjuvant chemotherapy of patients with high-risk stage I and II, as well as stage IIIA endometrial cancer. Further investigations are required to define the subgroup of patients who benefit from postoperative adjuvant chemotherapy. In addition, the optimal regimen remains to be defined as all of them (doxorubicin/cisplatin--AP, cyclophosphamide/ doxorubicin/cisplatin--CAP, paclitaxel/carboplatin--TC, paclitaxel/doxorubicin/cisplatin--TAP) cause significant toxicity. Thereby, combination of carboplatin plus paclitaxel represents an efficacious, low-toxicity regimen for managing intermediate-risk surgical stage I, as well as advanced or recurrent endometrial cancer.
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PMID:Risk factors and adjuvant chemotherapy in the treatment of endometrial cancer. 1840 82

Endometrial cancer generally has a good prognosis because most cases are diagnosed in stage I. It is possible to identify subgroups of patients with early stage endometrial cancer with a poor prognosis. Despite a traditional generous use of adjuvant radiotherapy those patients have less than an 80% 5-year overall survival. In this group there is a need for an effective systemic adjuvant therapy. Two randomised studies have shown better response rates but no significant difference in overall survival for doxorubicin-cisplatin vs doxorubicin in advanced or recurrent endometrial cancer. Mainly on the basis of the superior response rates, doxorubicin-cisplatin was for many years regarded as the standard chemotherapy in endometrial cancer. GOG-177 was the first phase III study on chemotherapy in advanced or recurrent endometrial cancer that showed a survival advantage. Paclitaxel-doxorubicin-cisplatin was better than doxorubicin-cisplatin, but the toxicity of the three-drug regimen has precluded general acceptance. Paclitaxel-carboplatin has rendered high response rates in endometrial cancer and is widely used, despite the lack of evidence based on randomised studies. GOG-122 was a pivotal randomised study that compared doxorubicin-cisplatin with whole abdominal radiotherapy in advanced optimally operated endometrial cancer and showed that chemotherapy with doxorubicin-cisplatin resulted in superior survival. Two recent studies have compared adjuvant chemotherapy (cyclophosphamide-doxorubicin-cisplatin) with adjuvant radiotherapy in early stage endometrial cancer. Both studies failed to show a difference between the treatments, but neither was powered to show non-inferiority. Another study (NSGO-EC-9501/EORTC-55991) compared adjuvant radiotherapy plus chemotherapy with adjuvant radiotherapy and showed better survival with the combination. The implications of these studies are discussed.
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PMID:Adjuvant chemotherapy in endometrial carcinoma: overview of randomised trials. 1846 80

Endometrial cancer is the most common gynecological malignancy in developed countries and represents the eighth leading cause of cancer related death in women. The growing incidence of endometrial cancer leads scientists and oncologists to identify effective preventive measures and also molecular markers for diagnosis and prognosis. Chemotherapy and hormone therapy is the mainstay treatment option for advanced and recurrent endometrial cancer and response to therapy is one of the most important factor which favors prognosis and overall survival. In recent years, there have been major advances in the treatment of patients with endometrial cancer. Despite advances made in the treatment of this cancer, the overall survival of patients has not significantly improved because considerable number of patients harbor tumor refractory to these therapies and the majority of the initially responsive tumors become refractory to treatments. Therefore, determination of sensitivity/resistance is becoming increasingly important for individualization of endometrial cancer therapy. The aim of this review is to present the existing knowledge about the molecular markers that could play a crucial role in determining resistance to chemo- and hormone therapy. Extensive literature search for the cell signaling pathways and factors responsible for chemoresistance have been performed and reviewed. Several recent studies suggest that deregulations in the apoptotic pathways (such as p53, Fas/FasL, Bcl-2 family proteins, inhibitor of apoptosis proteins), survival pathways (PI3K/AKT, MAPK), hormone receptor signaling pathways (progesterone receptor), Cyclooxygenase-2 and Her-2 are considered as key factors involved in the onset and maintenance of therapeutic resistance, suggesting that resistance is a multi-factorial phenomenon.
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PMID:Resistance to chemotherapy and hormone therapy in endometrial cancer. 1919 80

PURPOSE A phase II study was conducted to determine the response rate of ixabepilone (BMS-247550, National Cancer Institute (NCI)-supplied agent investigational new drug No. 59,699) in patients with persistent or recurrent endometrial cancer who have progressed despite standard therapy. PATIENTS AND METHODS Eligible patients had recurrent or persistent endometrial cancer and measurable disease. One prior chemotherapeutic regimen, which could have included either paclitaxel or docetaxel, was allowed. Patients received ixabepilone 40 mg/m(2) as a 3-hour infusion on day 1 of a 21-day cycle. Treatment was continued until disease progression or until unacceptable toxicity occurred. Results Fifty-two patients were entered on the study, and 50 of these were eligible. The median age was 64 years (range, 40 to 83 years). Prior treatment included radiation in 21 patients (42%) and hormonal therapy in eight patients (16%). All patients had prior chemotherapy, and 47 (94%) received prior paclitaxel therapy. The overall response rate was 12%; one patient achieved a complete remission (2%), and five achieved partial remission (10%). Stable disease for at least 8 weeks was noted in 30 patients (60%). The median progression-free survival (PFS) was 2.9 months, and the 6-month PFS was 20%. Major grade 3 toxicities were neutropenia (52%), leukopenia (48%), gastrointestinal (24%), neurologic (18%), constitutional (20%), infection (16%), and anemia (14%). CONCLUSION In a cohort of women with advanced or recurrent endometrial cancer who were previously treated with paclitaxel, ixabepilone showed modest activity of limited duration as a second-line agent.
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PMID:Phase II trial of ixabepilone as second-line treatment in advanced endometrial cancer: gynecologic oncology group trial 129-P. 1945 30

While early-stage endometrial cancer is highly curable after hysterectomy for the majority of patients afflicted with this disease, recurrent and metastatic endometrial cancer continues to pose a significant challenge. The median survival of women with advanced or recurrent uterine cancer on most recent clinical trials is only approximately 1 year. This review will discuss the developments of systemic therapy in recurrent endometrial cancer, focusing on North American trials, in particular those documenting recent progress in new drug developments, as well as the future of individualized treatment regimens.
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PMID:Systemic therapy for recurrent endometrial cancer: a review of North American trials. 1958 30


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