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

Gonadotrophin releasing hormone analogues (GnRHa) have been used to treat recurrent endometrial cancer. However, the mode of action is uncertain. Our previous studies showed no direct effect of GnRHa on endometrial cancer cell growth in vitro. We have now examined the effect of luteinizing hormone (LH) and follicle stimulating hormone (FSH) on endometrial cancer cell growth. The aim was to determine whether suppression of pituitary LH and FSH by GnRHa could explain the tumour regression seen in up to 44% of patients treated with this drug. We show that recombinant human LH and FSH (rhLH and rhFSH) produce a concentration dependent stimulation of the endometrial cancer cell line HEC-1A, in serum-free medium (maximum increase of 62 and 50% respectively relative to untreated controls). This increase is equivalent to that obtained by addition of 10% newborn calf serum. Growth of the Ishikawa cell line in culture increases in the presence of rhLH (maximum increase of 67%) but not with rhFSH. Using RT-PCR, we show that the Ishikawa cell line intermittently expresses receptor mRNA of LH but not of FSH; there is no expression of either mRNA by HEC-1A. Classically, both LH and FSH act via cAMP linked membrane receptors. However, neither rhLH nor rhFSH elicit cAMP production in either of our endometrial cancer cell lines. Thus, although a growth response to LH and FSH can be shown, and some cells express the LH receptor, stimulation appears to be via a pathway separate from that of the classical gonadotrophin receptor.
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PMID:Regulation of endometrial cancer cell growth by luteinizing hormone (LH) and follicle stimulating hormone (FSH). 1110 73

The concept that hormonal therapy may be useful in the treatment of endometrial cancer antedated the pharmaceutical availability of progestational compounds. By 1959, initial studies demonstrated the ability of progestins to reverse endometrial hyperplasias. Thereafter, progestins and other hormonal agents have been used in various roles as treatment for endometrial cancers. This chapter reviews the use of hormonal agents for the treatment of primary and metastatic/recurrent endometrial cancer, as well as such treatment in an adjuvant setting. Major problems in enhancing the efficacy of endocrine therapy of cancers arising from hormonally responsive tissues are also considered. The regulations of steroid-hormone receptor expression in endometrial and breast cancers continues to be an active area of research interest.
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PMID:Hormonal treatment of endometrial cancer: past, present and future. 1147 66

The median survival of women with advanced or recurrent endometrial cancer is less than one year. Only half the women with early stage endometrial cancer and poor prognostic factors such as high grade or deep myometrial invasion will survive for 5 years. Over the past decade, incredible strides have been taken in evaluating systemic therapy for this disease. However, survival rates remain poor. A literature search was conducted using CANCERLIT, EMBASE, Medline, Investigational Drug database (Current Drug Ltd.) and R&D Focus (IMSworld Publications). The references of the articles were also explored. Search terms included: endometrial cancer, chemotherapy, endocrine/hormonal therapies, molecular biologics, and specific drug names. Progestin therapy offers a 10-20% response rate and survival of less than 1 year. Progestins are most effective in women with well-differentiated tumours and a long disease-free interval. There is no role for adjuvant progestin therapy in early stage disease. Single-agent chemotherapy with the most activity includes ifosfamide, cisplatin/carboplatin, doxorubicin and paclitaxel. Combination chemotherapy provides a response rate of 40-60%; however, median survival is still less than a year. New areas of research include the identification and evaluation of new active endocrine therapies (i.e. LY353381.HCl and letrozole), chemotherapeutics (i.e. herceptin), evaluating chemotherapeutic agents in combination (i.e. paclitaxel, doxorubicin and platinum), in addition to radiation or instead of radiation. New avenues under development involve the specific molecules and pathways responsible for the initiation and growth of endometrial carcinoma, including: tumour suppressor genes, DNA mismatch repair genes, oncogenes, molecules involved in adhesion and invasion and angiogenesis. Further significant advances in radiotherapy, hormonal therapy and chemotherapy are unlikely. Exciting developments in understanding the molecules involved in tumour development and metastasis will allow the development of specific and selective inhibitors.
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PMID:Current status and future innovations of hormonal agents, chemotherapy and investigational agents in endometrial cancer. 1180 79

The best clinical outcomes for patients with endometrial cancer seem to be achieved with either surgery alone or a combination of surgery and radiation therapy. Although once administered preoperatively, irradiation is now rarely given prior to surgery in this population. After surgical staging, most patients receive postoperative adjuvant therapy based on their pathologic risk factors. Although prospective randomized trials in these patients are limited, recent studies have attempted to determine the best management strategies for the disease. Based on these investigations, treatment recommendations are outlined for patients who are surgically staged and for those with incomplete surgical staging. Also described is the use of irradiation in recurrent endometrial cancer after surgery alone, as well as palliative radiation. In addition, ongoing prospective randomized trials are described.
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PMID:Update on radiation therapy for endometrial cancer. 1208 99

Premenopausal women--especially young women--with endometrial cancer stage I may be treated successfully with progestins alone as primary therapy to preserve their child-bearing potential. There is some indication that progestins could be used in neoadjuvant fashion. Individualization of adjuvant treatment with radiation or progestins and in combination seems possible. Progestins have an established place in the palliative treatment of women with advanced cancer. In addition, progestins can be used in advanced and/or recurrent endometrial cancer in combination with chemotherapy and tamoxifen.
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PMID:Progestins and endometrial cancer. 1222 84

In North America, endometrial cancer is the most prevalent cancer of the female genital tract. On the basis of clinical and histologic variables, two main types of endometrial cancer have been described: Type I tumors, which are usually well differentiated and endometrioid in histology and account for the majority of cases; and Type II, which are poorly differentiated tumors, often with serous papillary or clear cell histology. Due to the early declaration of the disease by vaginal bleeding, approximately 80% of endometrial cancers are diagnosed at an early stage. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with or without lymph node dissection remains the cornerstone of treatment. Tumor stage, histologic grade and depth of myometrial invasion are the most important prognostic factors. If myometrial invasion to 50% or more of the myometrial width and/or grade 2 or 3 histology is present, pelvic radiotherapy is indicated to reduce the risk of pelvic recurrence. Postoperative radiation therapy may improve local control but does not affect survival for Stage I endometrial cancer patients. Systemic chemotherapy is typically reserved for women with disseminated primary disease or extrapelvic recurrence. Although the combination of cisplatin plus doxorubicin is commonly used, carboplatin plus paclitaxel represents an efficacious, low-toxicity regimen for managing advanced or recurrent endometrial cancer. Recently, a significant percentage of Type II uterine tumors have been found to overexpress the epidermal growth factor Type II receptor. Anti-HER-2/neu-targeted therapy might be a novel and attractive therapeutic strategy in patients harboring this biologically aggressive variant of endometrial cancer.
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PMID:Current treatment options for endometrial cancer. 1527 Jun 71

Recurrent endometrial cancer with both local and distant metastasis is very difficult to treat. A 55-year-old endometrial adenocarcinoma patient with bulky central recurrences and pelvic and inguinal lymph node metastases underwent laparotomy and paraaortic, pelvic and inguinal lymphadenectomy followed by concurrent chemoradiation (with cisplatin) to the paraaortic and inguinal lymph nodes as well as the whole pelvis. Neck and mediastinal lymph node metastasis emerged during treatment. Neck-node radiation and epirubicin was added followed by paclitaxel and carboplatin. Complete remission was achieved. Ten months later, isolated central re-recurrence happened and total pelvic exenteration was performed. The patient has survived without further recurrence for more than five years after the exenteration. Therefore, a multimodality approach with a combination of radical resection (even pelvic exenteration), radiotherapy and chemotherapy could be offered to well-selected patients with recurrent endometrial cancer despite out-of-field progression during therapy and in-field local failure to initial salvage treatment.
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PMID:Successful salvage treatment of recurrent endometrial cancer with bulky central tumor and extensive lymph node metastasis. A case report. 1559 56

The objective of this study was to evaluate the relationship between cervical cytology, histologic type, and risk of endometrial cancer recurrence. We performed a retrospective study of patients undergoing surgery for endometrial carcinoma. Risk factors for recurrence including histology, tumor grade, nodal status, myometrial invasion, peritoneal washings, stage, and cervical cytology were assessed. Abnormal cervical cytology was defined as the presence of any endometrial cells on Pap smear. Papillary serous and clear cell carcinomas were considered high-risk histologies. Univariate and multivariate analyses of risk factors for recurrence were performed. Thirty-nine (9%) patients developed recurrent endometrial cancer. More patients with abnormal Pap smears recurred (12% versus 4%, P < 0.05). For endometrioid adenocarcinoma, abnormal cervical cytology occurred in 61% and 7% recurred, while with high-risk histologies, 84% had abnormal cervical cytology and 19% recurred (P < 0.05). Other significant predictors of recurrence on univariate analysis were myometrial invasion, nodal status, washings, stage, and histology. On multivariate analysis, only nodal status remained a significant predictor of recurrence. Abnormal cervical cytology is associated with increased risk of endometrial cancer recurrence. Abnormal cervical cytology occurs more frequently in high-risk histologies, which are known to have a higher risk of recurrence. On multivariate analysis, only nodal spread remains a significant predictor of recurrence.
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PMID:Abnormal cervical cytology: a risk factor for endometrial cancer recurrence. 1588 79

Although paclitaxel is one of the most effective chemotherapeutic agents, its usefulness is still limited in advanced and recurrent endometrial cancer. Amifostine protection of normal tissues against the side effects of chemotherapeutic agents has been clinically proven in cancer patients; however, its application in endometrial cancer has not been fully evaluated. We have investigated the use of paclitaxel and amifostine in controlling the growth of poorly differentiated endometrial cancer cells, Hec50co, in vitro and in vivo. Our studies show that amifostine had direct anticancer effects on endometrial cancer cells in vitro by arresting the cell cycle at the G1 phase and inducing apoptosis. Amifostine also inhibited s.c. tumor growth in athymic mice. Paclitaxel IC50 value was reduced from 14 to 2 nmol/L with pretreatment of a single dose of 178 micromol/L of amifostine for 72 hours. Amifostine also synergized with paclitaxel in the arrest of the cell cycle at the G2-M phase and in the induction of apoptosis. This two-drug regimen inhibited s.c. tumor growth as well as improved mouse survival significantly more than paclitaxel alone. Amifostine also significantly improved paclitaxel-induced cytotoxic effects on peripheral blood profiles. Our studies show that amifostine has direct anticancer effects on endometrial cancer. Our data have also shown a potential anticancer synergy between amifostine and paclitaxel in vitro and in vivo, whereas amifostine maintained a protective role in peripheral blood profiles. The dual specificity of amifostine action should be further investigated.
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PMID:A potential synergistic anticancer effect of paclitaxel and amifostine on endometrial cancer. 1623 Apr 17

Hormonal therapy and chemotherapy play a major role in the management of advanced or recurrent endometrial cancer. Progesterone therapy obtains overall response rates ranging from 11% to 25% in patients with endometrioid-type tumours, and oral medroxyprogesterone acetate 200mg daily appears to be a reasonable therapeutic option for those lesions that are well differentiated and/or have a high progesterone receptor (PgR) content. However, the activity of progestins is often compromised by the down-regulation of PgR within the target tissues, and therefore therapeutic strategies designed to enhance PgR expression are warranted. Little data are currently available about the new aromatase inhibitors and selective estrogen receptor modulators. As for chemotherapy, the combination of doxorubicin [DOX]+cisplatin [CDDP] achieves overall response rates ranging from 34% to 60%, and the addition of paclitaxel (TAX) seems to improve response rates, progression-free survival and overall survival, but to worsen toxicity profile. A phase III study is currently comparing TAX+DOX+CDDP versus the less toxic combination of TAX+carboplatin. Chemotherapy is active against both endometrioid-type carcinoma and uterine serous papillary carcinoma. However, this latter endometrial malignancy is less chemosensitive than the histologically similar high-grade serous ovarian carcinoma. Interesting fields of research are represented by investigational agents directed against specific intracellular signal transduction pathways involved in the proliferation, invasiveness and metastatic spread of endometrial cancer. Mammalian target of the rapamycin (mTOR) inhibitors, epidermal growth factor receptor inhibitors (gefitinib, erlotinib, lapatinib, the monoclonal antibody cetuximab), imatinib, the monoclonal antibody trastuzumab, and the Clostridium perfrigens enterotoxin are currently under evaluation as molecularly targeted therapies for endometrial cancer. Further investigations addressed to better understand the signal transduction pathways that are disregulated in endometrial carcinogenesis could identify novel biological targets suitable for tailored therapies.
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PMID:Old and new perspectives in the pharmacological treatment of advanced or recurrent endometrial cancer: Hormonal therapy, chemotherapy and molecularly targeted therapies. 1643 30


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