Biomedical subjects

Laurie Elit

Publications and source records attributed to Laurie Elit.

11 recordsLinked to original sources

PubMed2006

Adjuvant radiotherapy in women with stage I endometrial cancer: a systematic review.

OBJECTIVE: To review the literature regarding the role of adjuvant radiotherapy (RT) in women with stage I endometrial cancer in terms of survival and pelvic control. METHODS: A systematic search of MEDLINE, EMBASE and the Cochrane Library databases was conducted for studies evaluating RT (1966 to October 2005). RESULTS: Five randomized trials were identified that evaluated adjuvant external beam radiotherapy (EBRT) and/or intracavitary radiotherapy (ICRT) including one in which women had undergone complete surgical staging. No survival differences were identified; however, none of the studies were powered enough to show a survival benefit. In three studies reporting subgroup analyses, intermediate-risk subgroups (stages IA and IB, grade 3 or stage IC) who received RT had fewer pelvic recurrences compared to women not receiving RT. Unfortunately, none of the studies reported ultimate pelvic control as an outcome. CONCLUSIONS: RT is not recommended in low-risk patients (stages IA, IB, grades 1 and 2). It is reasonable to consider EBRT for intermediate-risk subgroup patients (stage IC, grades 1 and 2, or stages IA, IB, grade 3), regardless of surgical staging, to reduce the risk of pelvic recurrence. EBRT is recommended for high-risk patients (stage IC, grade 3). The benefits of EBRT need to be weighed against the toxicity of treatment. Patients should be informed of the benefits and risks of EBRT. Additional analysis including ultimate pelvic control in subgroups would be helpful. More clinical trials are warranted to further define the role of EBRT in subgroups of patients and to clarify the role of ICRT.

Endometrial Neoplasms↗

PubMed2006

Follow-up after primary therapy for endometrial cancer: a systematic review.

OBJECTIVE: To determine the optimum follow-up of women who are clinically disease-free following potentially curative treatment for endometrial cancer. METHODS: A systematic search of MEDLINE, EMBASE and the Cochrane Library databases (1980 to October 2005) was conducted. Data were pooled across trials to determine overall estimates of recurrence patterns. RESULTS: Sixteen non-comparative retrospective studies were identified. The overall risk of recurrence was 13% for all patients and 3% or less for patients at low risk. Approximately 70% of all recurrences were symptomatic, and 68% to 100% of recurrences occurred within approximately the first 3 years of follow-up. No reliable differences in survival were detected between patients with symptomatic or asymptomatic recurrences nor were differences in patient outcomes reported by type of follow-up strategy employed. Detection of asymptomatic recurrences ranged from 5% to 33% of patients with physical examination, 0% to 4% with vaginal vault cytology, 0% to 14% with chest X-ray, 4% to 13% with abdominal ultrasound, 5% to 21% with abdominal/pelvic CT scan, and 15% in selected patients with CA 125. CONCLUSIONS: There is limited evidence to inform whether intensive follow-up schedules with multiple routine diagnostic interventions result in survival benefits any more or less than non-intensive follow-up schedules without multiple routine diagnostic interventions. Routine testing seems to be of limited benefit for patients at low risk of disease. Most recurrences tend to occur in high risk patients within 3 years, and most recurrences involve symptoms. The most appropriate follow-up strategy is likely one based upon the risk of recurrence and the natural history of the disease. Counseling on the potential symptoms of recurrence is extremely important because the majority of patients with recurrences were symptomatic. A proposed routine follow-up schedule is offered.

Disease-Free Survival↗

PubMed2006

The rapid uptake of concurrent chemotherapy for cervix cancer patients treated with curative radiation.

PURPOSE: In 1999, a series of clinical trials along with a clinical announcement from the National Cancer Institute (NCI) suggested that chemotherapy should be used concurrently with pelvic radiation in the management of cervical cancer. The purpose of this study is to examine the rate of chemotherapy use, in the province of Ontario, before and after these publications. METHODS: All incident cases of cervix cancer diagnosed between January 1, 1995, and March 31, 2001, were identified using the provincial cancer registry. These records were electronically linked to billing claims data and inpatient discharge abstract data. Patients receiving brachytherapy within 6 months of diagnosis were identified. The proportion receiving at least one injection of chemotherapy before brachytherapy was identified and compared in the "pre" and "post" publication group (April 1, 1999, cutoff). RESULTS: We identified 1039 cases as receiving curative radiation. In the pre cohort, 9.4% of patients received chemotherapy (95% CI, 7.3-11.4%) vs. 67.4% in the post cohort (95% CI, 61.8-73.0%). The change occurred abruptly in the first quarter of 1999. CONCLUSION: There was a significant increase in chemotherapy use after the publication of the NCI alert and related trials. Reasons for rapid uptake are discussed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

The quality of the operative report for women with ovarian cancer in Ontario.

OBJECTIVE: To assess the quality of the operative reports from cases of ovarian cancer surgery in Ontario. METHODS: We undertook a population cohort study including all newly diagnosed ovarian cancer patients treated initially with surgery from January 1996 to December 1998 in Ontario (n = 1341). We abstracted charts from hospitals and cancer centres. All surgical and pathology notes were abstracted into an ACCESS database. RESULTS: A total of 1,341 women had surgery as the first step in management of ovarian cancer. A vertical abdominal incision was used in 87.6% of these cases. Peritoneal cytology was obtained in 87.8% of cases overall, but in only 69.5% of stage 1 cases. A description of the ovaries was provided in 85% of reports, of the uterus in 70%, the diaphragm in 53%, the liver in 69%, the pelvic lymph nodes in 10%, and the para-aortic lymph nodes in 41%. In stage 1 cases, the ovaries were assessed histologically in 89% of cases, the uterus in 80%, the omentum in 69%, the peritoneum in 20%, the appendix in 9%, the pelvic lymph nodes in 10%, and the para-aortic lymph nodes in 7%. Frozen section was obtained in half of the stage 1 cases, and the false negative rate for identifying malignancy was 6%. In all, 23% of women received adequate surgical staging for stage 1 disease, and 12% of women with advanced disease had optimal debulking (to less than 1 cm residual disease). There are clear differences between centres with a gynaecologic oncologist on staff and other centres in the adequacy of surgical staging in women with stage 1 disease (chi2 = 60.6, P < 0.0001) and in optimal debulking for advanced disease (chi2 = 39.1, P < 0.0001). In 40% of cases with advanced disease, the amount of residual disease following surgery is not reported. CONCLUSION: The current approach of dictating operative notes does not provide sufficient detail in a large number of cases; this affects treatment decisions and limits our ability to assess quality indicators for operative care in ovarian cancer. This problem is pervasive but is more significant in centres without a gynaecologic oncologist.

Cohort Studies↗

PubMed2006

Drug evaluation: AP-23573--an mTOR inhibitor for the treatment of cancer.

ARIAD Pharmaceuticals Inc is developing intravenous and oral formulations of AP-23573, a rapamycin analog and inhibitor of mTOR (mammalian target of rapamycin) that blocks the proliferation and migration of vascular smooth muscle cells, for the potential treatment of cancer, including solid and hematological forms.

Animals↗

PubMed2004

Systematic review of adjuvant care for women with Stage I ovarian carcinoma.

BACKGROUND: Several adjuvant care interventions to treat women with Stage I ovarian carcinoma have been studied. The aim of the current systematic review was to determine the optimal strategy for adjuvant care for women with Stage I ovarian carcinoma. METHODS: A systematic search was conducted to find randomized controlled trials published between 1965 and April 2004 that examined adjuvant therapy (e.g., chemotherapy and radiotherapy) for women with Stage I ovarian carcinoma. RESULTS: Thirteen randomized controlled trials were identified that compared adjuvant therapies for women with Stage I ovarian carcinoma. Eight of these trials reported results only for patients with Stage I disease. The majority of patients in the five randomized trials that compared adjuvant chemotherapy with no chemotherapy did not receive lymphadenectomy as part of their surgical staging. The pooled results for Stage I patients indicated a survival benefit (relative risk [RR], 0.74; 95% confidence interval [CI], 0.58-0.94; P = 0.01), and a benefit in terms of a reduced risk of developing disease recurrence (RR, 0.70; 95% CI, 0.58-0.86; P = 0.0004) favoring adjuvant chemotherapy. Platinum-based adjuvant chemotherapy was reported to improve overall 5-year survival (absolute survival difference 8%; 95% CI, 2-12%; hazard ratio, 0.67; 95% CI, 0.50-0.90; P = 0.008). CONCLUSIONS: Adjuvant platinum-based chemotherapy for women with Stage I ovarian carcinoma improved survival and reduced the risk of recurrent disease. The optimally staged group accounted for approximately 10% of women with Stage I disease. The role of adjuvant chemotherapy in optimally staged patients (especially those with good prognostic factors) has not been assessed adequately.

Chemotherapy, Adjuvant↗

PubMed2004

Report of the 2003 pan-Canadian forum on cervical cancer prevention and control.

OBJECTIVE: To develop evidence-based consensus recommendations on the delivery of cervical cancer screening, human papillomavirus (HPV) education, HPV testing, and the optimal tool for cervical cytology within the Canadian health system. PARTICIPANTS: Leading up to a forum held in Ottawa on November 21 and 22, 2003, 254 registrants reviewed position papers through a Web-based discussion group. Experts in program management, clinical practice, epidemiology, public health, economics, and women's health, representing 48 organizations, then participated in the 2-day forum to develop consensus recommendations. EVIDENCE: Writing groups prepared position papers on optimal methods for cervical cytology; education concerning HPV; HPV testing in primary screening; HPV testing as a triage tool in cytopathology; and delivery mechanisms for cervical screening. Systematic reviews were the primary source of evidence supplemented by literature searches. CONSENSUS PROCESS: Feedback from Web-based discussions was incorporated into consecutive drafts of position papers. At the forum, recommendations and supporting evidence were presented, further debated in small-group sessions, and discussed in a plenary session. Despite divergent professional mandates and opinions, consensus was achieved on 15 recommendations across all areas. Final recommendations were posted to the Web for further input and circulated for written consensus by participants. CONCLUSIONS: The recommendations cover the use of new evidence and technologies in cervical cancer prevention in Canada and provide a framework for provision of HPV education, planning the implementation of new cervical screening technologies in Canada, the development of evaluation plans, and new research areas.

Canada↗

PubMed2002

A comparison of two prophylactic regimens for hypersensitivity reactions to paclitaxel.

OBJECTIVE: The aim of this study was to compare the rates of hypersensitivity reactions to paclitaxel with the conventional prophylactic regimen of two doses of oral corticosteroids and a modified regimen of a single dose of intravenous corticosteroid. METHODS: This was a retrospective historical cohort study assessing the rates of hypersensitivity reactions in patients receiving paclitaxel for ovarian or primary peritoneal carcinoma at the Hamilton Regional Cancer Centre from 1996 to 2000. Until 1998, all patients received the conventional prophylactic regimen consisting of two doses of oral dexamethasone (20 mg), 12 and 6 h prior to paclitaxel. From 1998 to the present, patients received a single dose of intravenous dexamethasone (20 mg), 30 min prior to paclitaxel. All patients also received an H(1) and H(2) blocker intravenously prior to paclitaxel administration. The analysis was corrected for potential covariates such as dose of paclitaxel and rate of infusion. The primary outcome measure was the rate of hypersensitivity reactions as defined by the National Cancer Institute of Canada-Clinical Trials Group. The Yates-corrected chi(2) test was used to compare the rates of these reactions, and a logistic regression analysis was used to determine whether any of the covariates were significant factors in these reactions. RESULTS: One hundred seven patients received the conventional corticosteroid prophylaxis prior to paclitaxel, and 110 received the single-dose intravenous corticosteroid prophylaxis. Of the 107 patients in the conventional prophylaxis group, 8 had a hypersensitivity reaction (7.5%), and only 1 of these was severe (0.9%). In contrast, of the 110 patients in the single-dose IV corticosteroid group, 19 had a hypersensitivity reaction (17.3%), and 8 of these were severe (7.3%). The difference in hypersensitivity reaction rates was significant (chi(2), P = 0.047). In the logistic regression analysis, the only significant factor related to hypersensitivity reactions was the type of prophylactic steroid regimen. CONCLUSIONS: In this series, the single-dose intravenous corticosteroid prophylactic regimen appeared to be associated with a higher rate of hypersensitivity reactions to paclitaxel than the conventional two-dose oral corticosteroid regimen.

Administration, Oral↗

PubMed2002

Referral patterns for gynaecologic cancers and precancerous conditions.

OBJECTIVES: (1) To determine a gynaecologist's preference for delivering primary surgical care to women with gynaecologic cancer or precancerous conditions; (2) to determine referral patterns for gynaecologic cancers and precancerous conditions; (3) to outline barriers to the current gynaecologic oncology service provision in Ontario; (4) to understand, from a gynaecologist's perspective, the acceptable waiting times from referral to subspecialty consultation; and (5) to determine a gynaecologist's interest in following patients after more specialized management for gynaecologic cancer. METHODS: The survey instrument was designed and pretested. The survey was mailed to 541 gynaecologists in Ontario. RESULTS: The response rate was 49.4%. Of the gynaecologists who responded, 75.3% trained in Ontario; 57.3% had community-based practices; and 55% indicated they surgically treated women with invasive cancers. The invasive cases treated most commonly were endometrial cancer (96.4%), followed by ovarian cancer (86.1%). Ninety-one percent of gynaecologists referred their patients to the closest cancer centre with a gynaecologic oncologist on staff. Seventy-five percent of gynaecologists were interested in delivering follow-up care for women who had treatment for cancer, provided that follow-up guidelines were made available. CONCLUSION: Gynaecologists were interested in providing follow-up care to women who received cancer care by subspecialists. Gynaecologists requested continuing education on gynaecologic cancers and guidelines for follow-up care. Issues surrounding the process of referral and communication with gynaecologists were seen as areas for improvement. The results of this survey will be pivotal in setting goals for a provincial gynaecologic oncology program.

Aftercare↗

PubMed2002

Current status and future innovations of hormonal agents, chemotherapy and investigational agents in endometrial cancer.

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.

Antineoplastic Agents, Hormonal↗

PubMed2002

CCI-779 Wyeth.

Wyeth Research (formerly Wyeth-Ayerst Research) is developing the sirolimus (rapamycin) analog CCI-779 as a potential treatment for various cancers [320924]. By November 2001, phase III trials had been initiated [428972], [429576]. In October 2001, Raymond James predicted filing in 2003, with a potential launch in 2005 [426718]. In March 2002, CCI-779, was designated for fast-track development by the FDA for the treatment of renal cell carcinoma after failure of initial therapy [442535]; at this time phase III trials for renal cell carcinoma and phase II trials for various solid tumors were ongoing [444030]. In March 2002, Wyeth revealed that filing was anticipated for 2004/2005 [443491]. In June and August 2001, Lehman Brothers predicted sales of US $40 million ($20 million in the US) in 2003, rising to US $75 million ($38 million in the US) in 2004 [418901], [420809]. In October 2001, analysts at Raymond James expected potential sales of the product at US $250 million [426718]. In May 2002, a patent (WO-00240000) was published claiming CCI-779 to be useful for the treatment of cancers of various origins, including renal, breast, cervical, uterine, head and neck, lung, prostate, pancreatic, ovarian, colon, lymphoma and melanoma.

Animals↗