Adjuvant Therapy In Endometrial Cancer Research Articles

RETIRED: The Role of Adjuvant Therapy in Endometrial Cancer

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

Antiproliferative and apoptotic effect of epigallocatechin-3-gallate on Ishikawa cells is accompanied by sex steroid receptor downregulation

Endometrial cancer is a significant malignancy in developed countries. Unopposed estrogen stimulation is considered as an important risk factor for endometrial cancer. Epigallocathechin-3-gallate (EGCG), biological active component of green tea, inhibits cancer cell proliferation. However, it is unknown whether EGCG has anticancer effects on endometrial cancer and what the molecular mechanism(s) are. We investigated the anticancer effects of EGCG on a human endometrial adenocarcinoma cell line (Ishikawa cells) with or without 17β-estradiol (E2) treatment. Cell proliferation assay was performed using 3-(4,5-dimethylthiaxol-2-yi)-2,5-diphenyltetraxolium bromide (MTT). The cell cycle was determined by flow cytometry and real-time analysis of cyclin and cdk genes. The apoptosis was measured by Annexin V-PI staining and real-time analysis of bcl-2, Bax and caspase genes. The MAPK signal, Akt and caspase-3 were determined by immunoblotting. Decreased estrogen and progesterone receptor expression was observed in EGCG-treated Ishikawa cells, and decreased MAPK signals and phospho-Akt were observed as well. EGCG caused the arrest of cells in the G0/G1 phase of the cell cycle. This compound interfered with Akt activation and MAPK signals, and increased apoptosis signals leading to a controlled caspases, Bcl-2, Bax genes and protein expression. Taken together, EGCG inhibits cell proliferation and induces apoptosis through Akt and MAPK signals. These findings suggest that EGCG may exert growth-inhibitory and apoptosis-inducing effects on endometrial cancer cells, accompanied by decreased estrogen and progesterone receptor. EGCG may have future clinical implications with respect to the development of novel approaches as an adjuvant therapy in endometrial cancer.

Controversies in the Adjuvant Therapy of Endometrial Cancer

Endometrial cancer is the most common malignancy of the female genital tract. Surgical treatment includes hysterectomy, bilateral salpingo-oophorectomy, and an appropriate staging procedure. Relapse of endometrial cancer may occur in patients with high risk factors, such as old age, grade 3 cancer, deep myometrial invasion, and papillary serous and clear cell types. In recent years, several randomized trials reported the results of adjuvant therapy for patients with high risk factors. Nonetheless, some controversies still exist. This paper presents and discusses the results of important randomized trials of adjuvant therapy for endometrial cancer with risk factors.

Adjuvant Chemotherapy in Endometrial Cancer

The indications for adjuvant therapy in endometrial cancer are briefly reviewed. The importance of systemic adjuvant therapy is emphasized. A short summary of randomized studies on adjuvant chemotherapy versus radiotherapy and on adjuvant sequential chemotherapy plus radiotherapy versus radiotherapy alone is given. On the basis of the present results from randomized trials, a combination of adjuvant radiotherapy and platinum-based chemotherapy seems to be most effective.

Adjuvant chemotherapy and chemoradiation following surgery for high-risk endometrial cancer.

5028 Background: Endometrial cancer with adverse pathology has a significant risk of disease relapse if treated with surgery alone. We performed a prospective phase II trial testing the addition of concurrent chemotherapy during adjuvant radiation followed by adjuvant chemotherapy. Methods: Eligible patients had histologically confirmed endometrial cancer following a minimum of TAH-BSO, plus high-risk features of: node-positive disease, grade 3 FIGO 1988 stage Ic or IIb, or any stage III disease. Stage IV disease, serous or clear cell cancer was excluded. Treatment involved 54Gy of external beam radiotherapy (RT) to the pelvis ±extended field (EFRT) with carboplatin AUC 2 weekly × 6 during RT, followed by 4 cycles of carboplatin AUC 5-6 and paclitaxel 175 mg/m2 q3weeks. The primary endpoint was failure-free survival (FFS), with secondary endpoints of overall survival (OS) and toxicity. Results: 41 patients of median age 57 (range 31-79) were enrolled 06/04 to 08/08. 24 (59%) had stage IIIC disease with 11 (27%) having residual measurable disease on post-operative CT. All completed planned RT, including 11 (27%) treated with EFRT. 32 (78%) received all 6 doses of concurrent chemotherapy, 32 all 4 cycles of adjuvant chemotherapy and 28 (68%) received the planned 10 doses. After a median follow-up of 2.34 years, the estimated 3 year FFS rate was 73% (95%CI: 54-87%) and OS rate was 93% (95%CI: 76- 98%). By the study censor date, 9 patients (22%) had a recurrence with only 2 patients relapsing within the RT field. Treatment was well tolerated with no treatment-related deaths. Grade 3 or 4 nonhaematologic toxicity occurred in 14 with 12% grade 3 diarrhoea and 10% grade 3 arthralgia/myalgia. One pt respectively developed febrile neutropenia and grade 3 sensory neuropathy with 4 (10%) developing platinum-hypersensitivity. Conclusions: Adjuvant chemotherapy after chemoradiation for patients with high-risk endometrial cancer is a promising approach, though distant failure remains the dominant site of failure. This regimen was well tolerated but the high number of carboplatin doses resulted in a 10% hypersensitivity rate. Ongoing randomised trials should be supported to determine the optimum adjuvant therapy in endometrial cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb

Use of the Sentinel Node Procedure to Stage Endometrial Cancer

Lymph node status is a major prognostic factor and a criterion for adjuvant therapy in endometrial cancer. The sentinel lymph node (SN) procedure has emerged as a possible alternative to systematic lymphadenectomy. The aims of this study were to determine the detection rate and the false-negative rate of the SN procedure, and its contribution to the staging of women with endometrial cancer. Forty-six patients with endometrial cancer underwent the sentinel node procedure followed by pelvic lymphadenectomy. SNs were detected with a dual or single labelling method in 39 and 7 cases, respectively. All SNs were analysed by both hematoxylin and eosin (H&E) staining and immunochemistry. SNs were identified in 40 patients (87%), whose mean number of SN was 2.6 (range 1-5). The SN detection rate was significantly lower with the single label than with the dual label (p = 0.01). Ten women (25%) had a positive SN on final histology (i.e. there were no false negatives). A correlation was observed between lymph node involvement and both histological grade (p = 0.01) and lymphovascular space involvement (p = 0.001). The stage predicted by magnetic resonance (MR) imaging correlated poorly with the Federation International of Gynaecology and Obstetrics (FIGO) stage. Among the ten women with a positive SN, three of the four women with a grade 1 tumour at biopsy had grade 2-3 disease on final histology. Seven of the ten women with a positive SN underwent external pelvic radiotherapy, based solely on their SN involvement. The SN procedure can reliably determine lymph node status in women with endometrial cancer. Given the limited capacity of MR imaging to detect myometrial invasion, and of biopsy to determine histological grade, our results support the systematic use of the SN procedure in women with endometrial cancer, including those with presumed early-stage disease and/or well-differentiated tumours.

5004 ORAL Survival risks and benefits with adjuvant therapy for endometrial cancer: systematic review and meta-analysis

5004 ORAL Survival risks and benefits with adjuvant therapy for endometrial cancer: systematic review and meta-analysis

Chemotherapy for high-risk early-stage endometrial cancer

To discuss the usefulness of chemotherapy in high-risk early-stage endometrial cancer and the best chemotherapy regimen. External radiation therapy has been successfully used to prevent local recurrence; however, it does not improve the overall survival and it increases the incidence of late toxicity. A recent randomized study revealed that adjuvant platinum-based combination chemotherapy might be a suitable alternative to radiotherapy for high-risk early-stage endometrial cancer. The optimal regimen is still in question because combinations of doxorubicin-cisplatin and paclitaxel-doxorubicin-cisplatin cause significant toxicity. The combination of paclitaxel-carboplatin may be better than doxorubicin-cisplatin with regard to toxicities. Radiation treatment following surgery has been the standard adjuvant therapy for endometrial cancer for a long time. Radiotherapy decreases the local recurrence rates; however, a significant impact on the overall survival has not been demonstrated. The usefulness of adjuvant chemotherapy has been demonstrated by only a little evidence. Nonetheless, we are encouraged by a recent randomized study. In light of the excellent outcomes associated with early-stage endometrial cancer, it is important to conduct another large randomized trial based on standardization of high-risk criteria to evaluate the efficacy of adjuvant chemotherapy.

2337: Acute Toxicity of Adjuvant Intensity Modulated Radiation Therapy With Chemotherapy in Endometrial Cancer

The role and type of adjuvant therapy in endometrial cancer remains controversial; the benefits of any adjuvant treatment must be weighed against potential toxicities. Thus, our objective was to determine the acute toxicity of adjuvant intensity modulated radiation therapy (IMRT) with and without adjuvant combination chemotherapy in patients with endometrial cancer.

American Brachytherapy Society survey regarding practice patterns of postoperative irradiation for endometrial cancer: Current status of vaginal brachytherapy

To survey the current postoperative recommendations for radiotherapy (RT) in patients with endometrial cancer, with an emphasis on vaginal brachytherapy (VBT). In August 2003, a 32-item questionnaire was mailed to a random sample of 2396 members of the American Society for Therapeutic Radiology and Oncology and the American Brachytherapy Society. The sample excluded members-in-training, physicists, and non-U.S. members. A follow-up mailing was conducted in November 2003. Those who had not treated any patient in the previous year for endometrial carcinoma were instructed to indicate so at the beginning of the questionnaire and return it without responding to any other item. Responses were tabulated to determine the relative frequency distribution. of the 2396 surveys sent out, 757 were returned, for a response rate of 31.6%. Of those who responded, 551 (72.8%) had performed postoperative irradiation for endometrial cancer and were included in this study. Of the 551 respondents, 99.8% had delivered external beam RT to some endometrial cancer patients. An increasing trend was found toward referrals for VBT; 91.5% of those who treated endometrial cancer performed VBT. The vaginal target most often irradiated was the upper vagina in 40.7%, upper 4-5 cm in 54.5%, and the entire vagina in 4.9%; 21.3% placed clips at the vaginal apex for applicator verification. The maximal dose to the bladder and rectum was recorded in 78.3% and 80.2% of patients, respectively. Of the respondents, 40% did not use low-dose-rate (LDR) VBT. The two most common LDR applicators were Delclos cylinders (29.7%) and Fletcher colpostats (29.3%). The mean boost dose delivered with LDR VBT when prescribed to the surface was 29.9 Gy and when prescribed to 0.5 cm was 23.8 Gy. When LDR therapy was used without external beam RT, the mean dose when prescribed to the surface was 56.8 Gy and when prescribed to 0.5 cm was 47.9 Gy. In 2002, 69.1% of respondents treated patients with high-dose-rate (HDR) VBT. Of the respondents, 90.6% used a single-channel vaginal cylinder, and 83.3% of cylinder users followed the curve of the cylinder to optimize dose, 67.9% adjusted the applicator position based on localization films, and 47% adjusted the applicator to be horizontal. The most common fractionation scheme when using HDR VBT as a boost was 5 Gy in three fractions prescribed to 0.5 cm (42.9%). The most common fractionation scheme used with HDR without external beam RT was 7 Gy in three fractions prescribed to 0.5 cm (41.8%). VBT is a common recommendation for postoperative adjuvant therapy for endometrial cancer. HDR appears to be the most popular approach, with a wide variety of dose fractionation schemes reported. Additional study is warranted to help define the ideal use of VBT.