Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platinum based chemotherapy is the cornerstone of treatment in advanced ovarian carcinoma. Paclitaxel, an unique antimicrotubule agent has shown significant clinical activity in cisplatin-resistant tumours, indicating a lack of cross-resistance. To compare the in vitro sensitivity of ovarian carcinoma to cisplatin and paclitaxel, we tested 7 ovarian carcinoma cell lines with the 96-well plate clonogenic assay. Chemosensitivity was expressed as the IC50 value i.e. the drug concentration causing 50% inhibition of clonogenic survival. IC50 values were obtained from dose-response curves after fitting the data to the linear quadratic equation. The IC50 values for paclitacel were 0.4-3.4 nM, showing an 8.5-fold difference between various cell lines. The IC50 values for cisplatin were 0.1-0.45 ug ml-1 showing only a 4.5-fold difference. This variance is clearly smaller than the 25-fold difference observed with the same method in endometrial carcinoma cell lines (Rantanen et al, Br J Cancer 69: 482-86, 1994). In accordance with clinical findings, no cross-resistance or correlation between sensitivity to paclitaxel and cisplatin could be demonstrated.
...
PMID:Paclitaxel and cisplatin sensitivity of ovarian carcinoma cell lines tested with the 96-well plate clonogenic assay. 871 94

Recurrent endometrial cancer has grave prognosis. Chemotherapy and hormonal therapy are mainstays of palliative treatment. Unfortunately the frequency of complete response and duration of progression-free interval are limited. This case report describes a patient with recurrent metastatic endometrial cancer who was initially treated with radiotherapy followed by surgery. Her recurrent tumor progressed during treatment with external radiation and a progestogen. She received paclitaxel (135 mg/m2 i.v. infusion over 24 h) and carboplatin (AUC 7.5 microg x h/ml) every 4 weeks with complete remission after 8 months which has persisted for 22 months. Paclitaxel and carboplatin combination should be considered for the treatment of endometrial cancer.
...
PMID:Prolonged remission of endometrial cancer with paclitaxel and carboplatin. 962 39

We have evaluated the growth inhibitory effects of paclitaxel alone or irinotecan (CPT-11) alone and their combined effects with other drugs on human endometrial cancer cell lines. IC50 doses of paclitaxel (Tx), SN-38 (active metabolite of CPT-11; 7-ethyl-10-hydroxycamptothecin) and cisplatin, including other drugs which have been used for treatment of patients with endometrial cancer, were examined using five human endometrial cancer cell lines (Ishikawa, HEC-1A, HEC-50B, HEC-59 and HEC-108). When in vitro sensitivity was defined IC50 lower than 10% of the peak plasma concentration (PPC), all endometrial cancer cell lines were sensitive to paclitaxel and three of five endometrial cancer cell lines were sensitive to SN-38, whereas cisplatin was not active against any endometrial cancer cell lines used in this study. Regarding the other drugs, aclarubicin (ACR) and actinomycin D (ACD) were active against four of five endometrial cancer cell lines, etoposide (VP-16) and pirarubicin (THP) against two, and 5-fluorouracil (5-FU) against only one, while ifosfamide (4-OHIFO) was not active against any endometrial cancer cell lines. When combined effects of paclitaxel or SN-38 with other one drug were determined by the median-effect analysis, paclitaxel followed by cisplatin resulted in synergistic effects to all endometrial cancer cell lines. Paclitaxel followed by SN-38 also had synergistic effects to four cell lines. Sequential but not simultaneous administration of taxol and THP-adriamycin showed synergistic effects to three cell lines. In combinations of SN-38 with other drugs, simultaneous administration of SN-38 and cisplatin resulted in synergistic effects to all cell lines. It is noteworthy that ACD followed by SN-38 showed synergistic effects to all cell lines, and simultaneous treatment of ACD and SN-38 or SN-38 followed by ACD also resulted in synergistic effects to three cell lines. THP-adriamycin followed by SN-38 had synergistic effects to four cell lines. The present quantitative data analysis for synergism provides a basis for a rational design of clinical protocols for combination chemotherapy in patients with endometrial cancer of the uterus.
...
PMID:In vitro sensitivity of human endometrial cancer cell lines to paclitaxel or irinotecan (CPT-11) in combination with other aniticancer drugs. 1103 61

Clear-cell carcinoma (CCC) and serous papillary carcinoma of the endometrium (UPSC) are rare subtypes of endometrial carcinoma (10%). The histological diagnosis can be made on the dilation and curettage specimens in both types in a very high percentage of the cases. This is important in the planning of treatment. CCC and UPSC are associated with about 50% of all relapses occurring in endometrial carcinoma, and the 5-year survival rate is, on average, 42% and 27% respectively. Surgico-pathological stage, age, and vessel invasion are independent prognostic factors for both groups. The recurrence rate is extremely high, and the most frequent extra-pelvic sites of relapse are the upper abdomen, lungs and liver. Stage Ia patients treated with complete surgical staging alone have a low risk of relapse and need not be offered adjuvant systemic therapy or pelvic radiation. The treatment of patients with CCC and UPSC stage Ib, Ic, II and III should include radical debulking surgery and some form of adjuvant therapy, but it is not clear which type is most effective. Adjuvant pelvic radiotherapy plus intracavitary radiotherapy is usually given in early-stage disease and pelvic radio therapy/or whole abdomen irradiation plus adjuvant systemic chemotherapy (PAC) in advanced disease. However, we are urgently waiting for a large prospective randomized study to compare both modalities. Paclitaxel, alone or in combination, is currently being tested in phase II studies.
...
PMID:Clear-cell and papillary serous cancer: treatment options. 1147 64

We evaluated the feasibility of weekly paclitaxel in patients with recurrent or advanced endometrial carcinoma who had failed treatment with cyclophosphamide, doxorubicin, and cisplatin (CAP). We treated four patients with CAP-resistant recurrent or advanced endometrial carcinoma with paclitaxel. Paclitaxel (80 mg/m(2); infused over 1 h) was administered weekly for a maximum of 18 weeks, unless disease progression or intractable toxicity developed. A complete response was observed in one patient and a partial response in two patients. Disease progression was found in one patient. Two patients developed grade 3 leukopenia or neutropenia. Neurotoxicity for all patients was within grade 1. Outpatient treatment with weekly paclitaxel was well-tolerated and feasible for patients with CAP-resistant recurrent or advanced endometrial carcinoma. Further trials to confirm the efficacy and toxicity of weekly paclitaxel are warranted.
...
PMID:Weekly paclitaxel in patients with CAP-resistant advanced or recurrent endometrial carcinoma: a series of four patients. 1613 74

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.
...
PMID:A potential synergistic anticancer effect of paclitaxel and amifostine on endometrial cancer. 1623 Apr 17

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.
...
PMID:Adjuvant chemotherapy in endometrial carcinoma: overview of randomised trials. 1846 80

Paclitaxel(referred to hereinafter as PTX )is used in ovarian cancer, non-small cell lung cancer, breast cancer, gastric cancer, and endometrial cancer with positive treatment result reports. However, severe allergic reactions such as decreases in blood pressure and impaired breathing occur with relatively high frequency. For the prevention of such allergic reactions, administration of a premedication composed of the three components, dexamethasone sodium phosphate injection, diphenhydramine hydrochloride tablet, and ranitidine hydrochloride injection solution(or injectable famodine), is advised in the appended documentation. Administration is difficult because, among these three components, only diphenhydramine hydrochloride is administered orally and thus must be provided through the internal medicine department. Particularly when this combined dosage is administered as outpatient chemotherapy, the doctor must prescribe diphenhydramine hydrochloride tablets, and the patient must not forget to bring them on the day in which chemotherapy is administered. Also, checks by the medical staff such as pharmacists and nurses are required, complicating the administration of this therapy further. Taking this situation into consideration, our hospital uses a short-time premedication method wherein d-Chlorpheniramine Maleate injections are substituted for diphenhydramine hydrochloride tablets, and the time required for premedication is reduced to 15 minutes. This study investigated the allergic reaction ratio to consider the safety and usefulness of the short-time premedication method used at our hospital. The chemotherapy regimens conducted for the subject patients were 9 cases of PTX+CBDCA, 6 cases of biweekly- PTX, and 5 cases of weekly-PTX. A total of 67 PTX injections were given, 15 of them being first-time administrations. The ratio of allergic/hypersensitivity reactions was 10.0%(2 cases in 20). The short-time premedication method using d-Chlorpheniramine Maleate injections did not display a significant difference from the conventional method used for prevention of allergic and hypersensitivity reactions. Also, since this method of medication proves useful for is easy for the patient, reduces treatment time, is safe, economical, and helps reduce the workload of doctors, pharmacists, and nurses.
...
PMID:[Evaluation of short-time premedication with d-chlorpheniramine maleate injection for paclitaxel-induced hypersensitivity reaction]. 1870 46

This paper covers an overview of the literature on the management of advanced endometrial cancer, concentrating on patients with histopathologic endometrioid type of tumors. The different treatment modalities are described and management recommendations are proposed.The standard surgical procedure includes an extrafacial total hysterectomy with bilateral salpingo-oophorectomy, collection of peritoneal washings for cytology, and exploration of the intraabdominal contents. In cases of extensive disease in the abdomen, an optimal surgical cytoreduction is associated with improved survival. Further treatment with radiotherapy may be indicated based on the pathological staging information to improve loco-regional control. Primary radiotherapy is indicated in cases where surgery is contraindicated. Systemic treatment can either be hormone therapy or chemotherapy. Progesterons are the cornerstone of hormone therapy. Prognostic factors for response are the presence of high levels of progesterone and estrogen receptors and low grade histology. Paclitaxel is the most active single agent drug. The combination therapy with paclitaxel and carboplatin is adopted as first choice in patients with endometrial cancer because of the efficacy and low toxicity, although not proven in a randomized trial.The literature on the management of patients with advanced endometrial cancer is discussed in detail. Each stage of advanced disease is presented separately, and management recommendations are proposed, and alternative approaches are given.Ongoing clinical trials are described, and the focuses of ongoing research are mentioned.
...
PMID:Management of surgical stage III and IV endometrioid endometrial carcinoma: an overview. 1940 72

Paclitaxel and carboplatin are commonly used and well-tolerated agents for gynecologic malignancies. The persistence of platinum in human tissues for 14 days and the long-term retention of platinum in tissues for up to 17 months have been reported. Paclitaxel remains in human uterine cervical cancer tissues for 6 days. These findings prompted us to determine the retention of paclitaxel and carboplatin in human uterine cervical carcinoma, endometrial carcinoma, ovarian carcinoma, and pelvic lymph nodes to establish baseline parameters and guide the development of more effective treatment interventions. Thirty patients with uterine or ovarian carcinomas were treated with intravenous weekly paclitaxel-carboplatin chemotherapy before surgery. The concentrations of these agents in carcinoma tissue, normal cervical, myometrial and ovarian tissues, and pelvic lymph nodes were measured 5 days after the final administration. Paclitaxel was specifically retained in cervical, endometrial, and ovarian carcinoma tissues but was not detected in lymph nodes. In contrast to paclitaxel, carboplatin was readily detectable with similar levels in all tumor-associated and normal host tissues. In addition, a low paclitaxel concentration in cervical carcinoma tissue was significantly associated with short progression-free survival and overall survival. Further studies are needed to clarify the tissue distribution of anticancer drugs in humans and promote optimal treatment strategies enhancing paclitaxel lymphatic targeting.
...
PMID:Intravenous paclitaxel is specifically retained in human gynecologic carcinoma tissues in vivo. 1950 40


1 2 3 Next >>