PubMed Health⌕ Search

Biomedical subjects

Allan Covens

Publications and source records attributed to Allan Covens.

14 recordsLinked to original sources
PubMed2007

Cytoreductive surgery for recurrent ovarian cancer.

PURPOSE OF REVIEW: The issue facing clinicians managing ovarian cancer has evolved over the past three decades from treatment for cure and subsequently palliation, to prolongation of survival for most patients. The purpose of this paper is to review the data, rationale, and issues surrounding cytoreductive surgery in recurrent ovarian cancer and its potential role in this new paradigm shift. RECENT FINDINGS: Abundant retrospective series report prolongation of survival with secondary cytoreductive surgery in recurrent ovarian cancer. Selection bias, publication bias, and subsequent therapies, however, are confounding factors for survival. As management of ovarian cancer has recently evolved to a treatment of a 'chronic disease', surgery (which has a definite role in primary therapy) should be considered. SUMMARY: No prospective randomized studies have been performed to date, and therefore adoption of this method of management has been limited. The absence of good data leaves clinicians without clear direction on how to best manage patients. Patients with favorable characteristics such as a long disease-free interval, good performance status, a single or few small intra-abdominal recurrences may benefit from secondary cytoreduction. A prospective randomized study is needed.

Female↗
PubMed2006

Phase II trial of pulse dactinomycin as salvage therapy for failed low-risk gestational trophoblastic neoplasia: a Gynecologic Oncology Group study.

BACKGROUND: The purpose of the study was to determine the activity and toxicity of pulse dactinomycin as salvage treatment of patients with low-risk gestational trophoblastic neoplasia (GTN) who failed methotrexate therapy. METHODS: Eligible patients had persistent/recurrent low-risk GTN defined by changes in serum human chorionic gonadotropin (hCG) levels (<10% fall over 3 consecutive weekly titers, >20% rise over the previous value, or a rise after attaining institutional normal [>5 mu/mL]); World Health Organization (WHO) score 2-6; Gynecologic Oncology Group (GOG) performance status 0-1; and previous treatment restricted to methotrexate. Dactinomycin administration was 1.25 mg/m2 intravenous (i.v.) every 2 weeks until documented complete response (CR) or treatment failure. CR was defined as an institutional normal serum hCG level sustained for >or=4 consecutive weeks; treatment failure was a <10% fall (3 assays over 4 weeks) or >20% rise (over previous value) in hCG serum level. Levels were monitored biweekly x 8 weeks beyond the first normal value, then monthly x 10. RESULTS: Five of 44 enrolled patients were ineligible due to choriocarcinoma and normal pretreatment serum hCG level (2 each), no history of methotrexate (1), and 1 patient with documented phantom hCG syndrome was unevaluable. In all, 28 of 38 (74%) evaluable patients attained CR. The median number of cycles was 4 (range, 2-10). Severe toxicity was minimal, causing no patient to discontinue therapy. All treatment failures achieved a CR after receiving subsequent chemotherapy; 3 patients also underwent hysterectomy. CONCLUSION: Pulse dactinomycin is an active regimen for patients with low-risk GTN who fail previous methotrexate therapy.

Adult↗
PubMed2006

Chemotherapy-induced alterations in ovarian sex cord tumor with annular tubules (SCTAT): a diagnostic challenge.

We present a case of ovarian sex cord tumor with annular tubules (SCTAT) in a patient that received neoadjuvant chemotherapy with 3.5 years of follow-up. Neo-adjuvant chemotherapy is a common practice in advanced cases of ovarian carcinoma and is rarely applied in nonepithelial ovarian tumors. Chemotherapy-induced morphologic alterations of the subsequently resected tissue samples are well recognized; in this case, chemotherapy-induced cytoarchitectural changes created diagnostic difficulties in the subsequently resected specimen.

Adult↗
PubMed2006

Cyclooxygenase-2 (COX-2) immunostaining does not correlate with the degree of vulvar neoplasia.

OBJECTIVE: The cyclooxygenase-2 (COX-2) enzyme is up-regulated in inflammatory and neoplastic conditions. In the last decade, its biological role has been investigated in various pre-invasive and invasive cancers with the hope that it can serve as a target for cancer prevention and treatment. METHODS: We evaluated the expression of COX-2 in vulvar biopsies to determine its relationship to the degree of dysplasia. COX-2 expression was studied by immunohistochemistry in 62 consecutive vulvar biopsies divided into four diagnostic groups. Group 1 included inflamed vulva (n = 14); group 2, vulvar intraepithelial neoplasia (VIN) I and VIN II (n = 20); group 3, VIN III and carcinoma in situ (n = 18); and group 4, invasive squamous cell carcinoma (n = 10). Representative sections were immunostained using polyclonal anti-COX-2 antibodies at concentration 1:25 without pretreatment. Immunostaining was scored according to the proportion of positive epithelial cells in the vulvar mucosa as 0 (no positive cells), 1(< 5% positive), 2 (6-50% positive), or 3 (> 50% positive). RESULTS: Mean immunostaining scores were 1.6, 1.4, 0.7, and 1.2 for groups 1, 2, 3, and 4, respectively. Scores were different between the groups (chi(2) = 9.908, P = 0.019) as shown by Cochran-Mantel-Haenszel statistical analysis (modified ridit scores), but did not correlate with age or the degree of dysplasia. The strongest staining for COX-2 was in the inflammatory group. CONCLUSION: COX-2 staining in inflamed, dysplastic, and malignant vulvar epithelium is variable but, as shown in this study, does not correlate with the degree of vulvar dysplasia or malignancy.

Adult↗
PubMed2005

A phase II evaluation of tirapazamine plus cisplatin in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer: a Gynecologic Oncology Group study.

OBJECTIVES: To estimate the anti-tumor activity, nature and degree of toxicity of tirapazamine in combination with cisplatin in patients with recurrent platinum-sensitive ovarian or primary peritoneal cancers. METHODS: Eligible consenting patients had to have recurrent epithelial ovarian or primary peritoneal carcinoma with measurable disease. Patients were not allowed to have received any additional cytotoxic chemotherapy for management of recurrent or persistent disease, including re-treatment with initial chemotherapy regimens. Patients must have been platinum-sensitive, meaning a treatment-free interval of >6 months after response to a platinum-based regimen. The RECIST criteria were used for parameters of response. Tirapazamine was administered at a dose of 390 mg/m2 IV over 2 h followed 1 h later by cisplatin 60 mg/m2 IV every 3 weeks until disease progression or adverse effects prohibited further therapy. RESULTS.: Between June 2001 and February 2004, 65 patients were entered onto this study by 27 institutions; one patient was excluded due to ineligible tumor type. Twenty-six patients (41%) received six or more cycles of therapy; however, 16 (25%) received one course of therapy (mainly due to side effects or patient request). There were six (9%) complete responders and 28 (44%) partial responders for a total response rate of 53%. Only two patients (3%) developed increasing disease on this protocol, and response could not be assessed in 18 patients (28%). The median progression-free and overall survival for all patients is 10.9 and 26.4 months, respectively. The regimen did not cause major hematologic toxicity, however, it did cause frequent constitutional (23%) and gastrointestinal (mostly nausea/vomiting) (44%) grade 3 or 4 toxicity. CONCLUSIONS: The combination of tirapazamine and cisplatin has definite activity in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer. However, toxicity, primarily non-hematologic, was substantial. Reducing the toxicity of a tirapazamine-platinum combination should be pursued in future trials.

Adult↗
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

Successful salvage of relapsed high-risk gestational trophoblastic neoplasia patients using a novel paclitaxel-containing doublet.

OBJECTIVE: To describe one institution's results with a novel 3-drug doublet, consisting of paclitaxel, etoposide and cisplatin, for salvage of relapsed high-risk gestational trophoblastic neoplasia (GTN) patients. STUDY DESIGN: Analysis of treatment results with the doublet regimen in two patients with recurrent/persistent high-risk choriocarcinoma in the Division of Gynecologic Oncology, Toronto-Sunnybrook Regional Cancer Centre, University of Toronto. Both patients had been treated previously with one or more of the doublet drugs. RESULTS: Both patients experienced complete responses, patient 1 for 13 months and patient 2 for 9. Patient 1 required surgical resection of a single focus of recurrence and was again in complete remission 27 months after completing her last course of doublet chemotherapy. Patient 2 has not relapsed since completing the treatment. CONCLUSION: The doublet regimen appears capable of producing a sustained response in patients with recurrent high-risk GTN who have previously undergone extensive chemotherapy. Further, the regimen seems to be reasonably well tolerated.

Adult↗
PubMed2003

Histopathologic score predicts recurrence free survival after radical surgery in patients with stage IA2-IB1-2 cervical carcinoma.

BACKGROUND: The authors evaluated clinical and pathologic factors that predicted for recurrence after patients underwent radical surgery for International Federation of Gynecology and Obstetrics (FIGO) Stage IA(2)-IB(1-2) cervical carcinoma and developed a simple method of scoring those predictive factors to quantify outcome. METHODS: An analysis was conducted of a prospective radical surgery cervical carcinoma data base. A Cox proportional hazards regression analysis was done for each of the individual factors to estimate individual risk ratios using all available data for each factor. Stepwise and best-model options were used to identify the best combinations as predictors and to calculate adjusted risk ratios. Based on the information obtained, each patient was assigned a categorical score to predict recurrence. The variables used for the score were dichotomized. The differences between the scores in time to recurrence were evaluated using the log-rank test to compare the time to recurrence curves that were generated with the Kaplan-Meier method. RESULTS: Eight hundred seventy-one patients were included in the study, and 66 patients who developed recurrent disease after a median follow-up of 49 months. Tumor size, maximum depth of invasion, pelvic lymph node status, tumor grade, and capillary lymphatic space (CLS) were single predictors for recurrence, and the score, which was based on combinations of these factors, predicted the disease free survival. Maximum depth of invasion, pelvic lymph node status, and CLS were the best combined predictors for recurrence, and they were used to form a second, precise scoring system to predict disease free survival (P < 0.0001; log-rank test). CONCLUSIONS: The scoring system based on maximal depth of invasion, CLS, and pelvic lymph node metastases identified four strata of patients with distinct recurrence free survival. The incremental presence of each factor decreased recurrence free survival after patients underwent radical surgery. Patients with the presence of all three factors had a 5-year recurrence free survival rate of 65%. These patients would be suitable for studies of postoperative adjuvant therapy to improve outcome.

Adult↗
PubMed2003

Phase II trial of danazol in advanced, recurrent, or persistent endometrial cancer: a Gynecologic Oncology Group study.

OBJECTIVES: To evaluate the activity and toxicity of danazol in advanced, recurrent, or persistent endometrial carcinoma. METHODS: Eligible patients with advanced, recurrent, or persistent endometrial carcinoma not amenable to curative therapy were treated with danazol at a dose of 100 mg four times per day until disease progression or toxicity necessitated discontinuation. Eligibility criteria included the presence of measurable disease and no prior chemotherapy. Immunohistochemical analysis of metastatic tumor tissue for estrogen and progesterone receptors was required. RESULTS: Twenty-five patients were enrolled and 3 were excluded. Six patients had tumors staining positive for both estrogen and progesterone receptors. There were no responders among 22 eligible patients. Six patients (27%) demonstrated stable disease as their best response. The median progression-free survival and overall survival were 1.9 and 14.4 months, respectively. A median total dose of 21.7 (range: 1.4 to 67.2) of danazol was administered. Therapy was discontinued in 5 eligible patients due to toxicity. Four of these patients experienced hepatic toxicity. CONCLUSIONS: Danazol has minimal activity in advanced, recurrent, or persistent endometrial carcinoma.

Aged↗
PubMed2003

Slide review in gynecologic oncology ensures completeness of reporting and diagnostic accuracy.

OBJECTIVE: We reviewed patient records in our tertiary care teaching hospital to assess the value of the mandatory slide review policy in gynecologic oncology with emphasis on completeness of reports. METHODS: Cases reviewed between October 2001 to September 2002 were studied. Clinical information was gathered from discussions at the weekly tumor board and from chart review. The standardized reporting guidelines in benchmark surgical pathology textbooks were used to assess the completeness of original pathology reports of excisional specimens. Diagnostic discrepancies were classified as major if the resultant change led to alteration of management or minor if it did not. RESULTS: Three hundred fifty-one cases were reviewed; 173 biopsies and 178 excisional specimens. Only 140 (78.7%) of the original pathology reports of the latter group conformed to standardized reporting guidelines. Of the 38 incomplete reports, 18 were missing critical information necessary for planning of further therapy, representing 10.1% of reports of all excisional specimens. We agreed with the original diagnosis in 252 cases (71.8%). Minor discrepancies were noted in 70 (19.9%) and major discrepancies in 29 cases (8.3%). No major discrepancy resulted from reviewing any of the vulvar specimens or cases that were already reviewed by gynecologic pathologists of other academic institutes. CONCLUSION: Mandatory slide review in gynecologic oncology is an important component in the management of gynecologic cancer patients because it completes reporting on missing parameters required for planning subsequent therapy in 10.1% of cases and recognizes discrepancies altering management in 8.3% of patients.

Female↗
PubMed2003

Pregnancy outcomes in patients after radical trachelectomy.

OBJECTIVES: This study was undertaken to review and analyze the fertility and pregnancy outcomes in patients who have undergone radical trachelectomy as the method of management of invasive carcinoma of the cervix. STUDY DESIGN: All preoperative, operative, and follow-up data were collected prospectively. Perinatal information was completed by chart reviews and patient questionnaires. RESULTS: Of 80 patients having undergone the above procedure, 39 have attempted to conceive for a median of 11 months (range 1-85). There have been a total of 22 pregnancies in 18 patients (4 patients pregnant twice). Of the 22 pregnancies, 18 were viable, with 12 progressing to term and delivering by caesarean section. Preterm premature rupture of membranes was the primary cause of preterm delivery. CONCLUSION: This series confirms that pregnancy is a safe and realistic outcome for women undergoing radical trachelectomy for invasive carcinoma of the cervix. Given the apparently high incidence of preterm premature rupture of membranes, these pregnancies should be managed as high risk.

Adult↗
PubMed2002

Systematic review of first-line chemotherapy for newly diagnosed postoperative patients with stage II, III, or IV epithelial ovarian cancer.

OBJECTIVE: The aim of this study was to determine the optimal postoperative chemotherapy regimen for women with newly diagnosed stage II, III (micro or macro), or IV epithelial ovarian cancer. METHODS: A systematic search was conducted to find randomized controlled trials and meta-analyses published between 1980 and April 2001. RESULTS: A published meta-analysis found that, compared with non-platinum-based regimens, platinum, alone or in combination with other agents, improved survival when used as first-line chemotherapy for ovarian cancer. The meta-analysis did not detect a difference in efficacy between cisplatin and carboplatin. A published randomized trial of cisplatin plus paclitaxel versus carboplatin plus paclitaxel did not detect a significant difference in survival between these regimens. In two randomized trials, treatment with paclitaxel plus cisplatin resulted in improved survival compared with cyclophosphamide plus cisplatin. A randomized trial of paclitaxel plus cisplatin versus paclitaxel alone versus cisplatin alone detected no differences in survival among the three treatment groups. While hematologic adverse effects were more frequent with carboplatin than with cisplatin, nonhematologic adverse effects were less frequent with carboplatin. The addition of paclitaxel to cisplatin did not appear to increase the incidence of serious adverse effects. CONCLUSIONS: Intravenous carboplatin plus paclitaxel is the recommended postoperative chemotherapy regimen for newly diagnosed stage II-IV epithelial ovarian cancer. Intravenous cisplatin plus paclitaxel may also be considered a treatment option. Intravenous carboplatin as a single agent may be considered a treatment option in patients for whom paclitaxel is contraindicated or in patients who are unwilling to accept the adverse effects of paclitaxel chemotherapy.

Antineoplastic Agents↗
PubMed2002

Is there a role for pelvic lymph node debulking in advanced cervical cancer?

OBJECTIVE: The purpose of this study is to determine if a survival advantage exists from surgical debulking of enlarged pelvic lymph nodes in advanced cervical cancer. METHODS: Using information from studies published on the topic of debulking lymph nodes in locally advanced cervical cancer along with baseline control rates of standard treatment and patterns of failure, an estimate of how many patients with bulky pelvic lymph node disease would benefit from this procedure was calculated. The design and feasibility of a randomized trial to test this intervention is also discussed. RESULTS: Based on our calculations 1, 2, and 4% of stage IB, IIB, and IIIB patients, respectively, would benefit from a debulking procedure. Based on our calculations with such small differences in survival along with other inclusion and exclusion criteria, a randomized trial, which would compare chemoradiation to chemoradiation and surgery, would require anywhere from 10,000-30,000 patients per arm. CONCLUSIONS: A very small fraction of patients would benefit from a surgical debulking procedure of pelvic nodes. A randomized controlled trial to test this research question is not feasible. A subset population is identified which may benefit from a debulking approach.

Algorithms↗