National Cancer Institute®
Last Modified: July 1, 2002
UI - 11914645
AU - Schoemaker NE; Herben VM; de Jong LA; van Waardenburg RC; Pluim D; ten
TI - Bokkel Huinink WW; Beijnen JH; Schellens JH Topoisomerase I levels in white blood cells of patients with ovarian cancer treated with paclitaxel-cisplatin-topotecan in a phase I study.
SO - Anticancer Drugs 2002 Jan;13(1):87-91
AD - Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. APNSC@SLZ.nl
Topotecan stabilizes the topoisomerase I (Topo I) cleavable complex. We measured Topo I levels in white blood cells of patients with ovarian cancer treated with topotecan. Topotecan was given i.v. daily x 5 q 3 weeks in combination with paclitaxel (1 day before topotecan) and cisplatin (just prior topotecan). Our aim was to correlate Topo I levels to pharmacokinetics and toxicity. Topo I levels were determined using Western blotting and were expressed relative to the Topo I level present in 10 microg cell lysate of the human IGROV1 ovarian cancer cell line. We found no correlation between Topo I levels and (non-)hematological toxicity. Topo I levels after the fifth topotecan infusion were significantly negatively correlated with the AUC of topotecan (R = -0.64, p = 0.026), in contrast with Topo I levels prior to (R = -0.25, p = 0.4) and after (R = -0.30, p = 0.3) the first topotecan infusion. Topo I levels after the fifth topotecan infusion (48 +/- 27%, mean +/- SD) were higher than Topo I levels prior to and after the first topotecan infusion (3.0 +/- 4.7 and 2.7 +/- 3.6%, respectively) (p = 0.001). In conclusion, we detected a significant inverse correlation between Topo I level and topotecan AUC at day 5, and we found increasing Topo I levels during a daily x 5 schedule of treatment with topotecan.
UI - 11895897
AU - Seiden MV; Ng SW; Supko JG; Ryan DP; Clark JW; Lynch T; Huang KC;
TI - Kwiatkowski D; Skarin A; Eder JP Jr A phase I clinical trial of sequentially administered doxorubicin and topotecan in refractory solid tumors.
SO - Clin Cancer Res 2002 Mar;8(3):691-7
AD - Department of Medicine, Massachusetts General Hospital, Boston 02114, USA. firstname.lastname@example.org
PURPOSE: To determine whether agents that target topoisomerase I and II could be administered sequentially. DESIGN: A Phase I study was conducted to evaluate sequential treatment with bolus IV doxorubicin followed 48 h later by topotecan given as a 30-min i.v. infusion on 3 consecutive days, with additional cycles of therapy repeated every 3 weeks. Characteristics of the 22 patients entered into the study were: 13 male and 9 female; median age, 49.5 (range 33-66) years; Eastern Cooperative Oncology Group performance status, 0-1; and normal cardiac, hematological, hepatic, and renal function. All patients had received prior therapy (median >or=2 prior regimens). RESULTS: The maximum tolerated dose of the combination was 25 mg/m(2) doxorubicin and 5.25 mg/m(2) topotecan (1.75 mg/m(2)/day x 3). Neutropenia was the dose-limiting toxicity. Attempts to further escalate the dose using 5 microg/kg granulocyte colony-stimulating factor proved unsuccessful because of thrombocytopenia. Among the 17 patients who were evaluable for response, 6 had a partial response, and 4 showed evidence of disease stabilization. The partial responses occurred in patients with small cell lung cancer (3 of 7), non-small cell lung cancer (1 of 6), esophageal adenocarcinoma (1 of 2), and ovarian carcinoma (1 of 1), and it lasted for 3-6 months. Administration of doxorubicin 2 days before topotecan did not alter topotecan pharmacokinetics. Changes in topoisomerase mRNA levels were observed during chemotherapy. CONCLUSIONS: The sequential combination of doxorubicin followed by topotecan is highly active in several chemotherapy refractory long, ovary, and esophageal cancers. Despite significant neutropenia, toxicity is manageable and well tolerated. Phase II trials to further evaluate the efficacy of this promising combination regimen against non-Hodgkin's lymphoma and lung cancer have been initiated.
UI - 11916245
AU - Bonovich M; Olive M; Reed E; O'Connell B; Vinson C
TI - Adenoviral delivery of A-FOS, an AP-1 dominant negative, selectively inhibits drug resistance in two human cancer cell lines.
SO - Cancer Gene Ther 2002 Jan;9(1):62-70
AD - Laboratory of Metabolism, Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Activator protein-1 (AP-1) transcription factor has been linked to chemotherapeutic resistance. To assess the clinical efficacy of AP-1 inhibition toward reversing drug resistance, we have developed an adenovirus expressing a dominant negative that inhibits AP-1 DNA binding, namedAdA-FOS. We examined the consequence of AdA-FOS infection on two paired human cancer cell lines, each pair consisting of a parental cell and the drug- resistant derivative. The first pair of cells is the parental human ovarian cancer cell line A2780 and the cisplatin-resistant A2780/CP70 cell line. The second pair of cells is the parental epidermal carcinoma cell line KB8 and the multidrug-resistant (mdr) KB85 cell line. Because of an association of up-regulated AP-1 activity with their drug resistance, these cell lines were considered good targets of AdA-FOS therapy. Following infection of the drug-sensitive and drug-resistant cells, we observed a significant decrease in cell viability of KB85 and A2780/CP70 cells at drug doses normally not lethal to the cell. The parental cell lines, A2780 and KB8 cells, were not similarly affected by AdA-FOS. This decrease in viability was specific to AdA-FOS as an adenovirus control (Advector) did not reverse drug resistance. Although the efficiency of AdA- FOS in therapy would need to be further analyzed with other cisplatin-resistant and mdr cell lines, these results suggest that AP-1 is a therapeutic molecular target and that inhibition of AP-1 DNA binding may be of clinical value in treating chemotherapeutic resistance.
UI - 12047311
AU - Kurata H; Takakuwa K; Tsuneki I; Aoki Y; Tanaka K
TI - Ovarian tumor cell detection in peripheral blood progenitor cells harvests by RT-PCR.
SO - Acta Obstet Gynecol Scand 2002 Jun;81(6):555-9
AD - Department of Obstetrics and Gynecology, Faculty of Medicine, Niigata University, Japan. email@example.com
BACKGROUND: To evaluate the frequency of tumor cell contamination in autologous peripheral-blood progenitor cells from patients with ovarian cancer, and to determine the impact of infusing such cells on relapses after high-dose chemotherapy. METHODS: Seventy-three samples of peripheral-blood progenitor cells from 24 ovarian cancer patients were studied for contaminated tumor cells by cytokeratin 7 and cytokeratin 20 reverse transcriptase polymerase chain reaction. RESULTS: Tumor cell contamination in peripheral-blood progenitor cells was detected in 11 of 24 patients (46%) and, among these, in four of 11 patients who received transplantations of peripheral-blood progenitor cells. There was no trend towards longer relapse-free survival in patients infused with cytokeratin-negative peripheral-blood progenitor cells as compared with positive ones. Interestingly, two of four patients who received transplantations of peripheral-blood progenitor cells containing tumor cells were free from progression at 20 and 41 months after transplantation. CONCLUSION: Tumor cell contamination of peripheral-blood progenitor cells was frequently noted by transcriptase polymerase chain reaction in patients with ovarian cancer. The biological and clinical significance of this finding remains to be elucidated.
UI - 12053883
AU - Lehoczky O; Bagameri A; Lehoczky G; Pulay T
TI - [Early results of topotecan therapy in patients with recurrent ovarian cancer]
SO - Orv Hetil 2002 Apr 21;143(16):825-8
AD - Nogyogyaszati Onkologiai Osztaly, Orszagos Onkologiai Intezet, Budapest. firstname.lastname@example.org
INTRODUCTION: Topotecan inhibits the topoisomerase-I enzyme resulting its stabilisation on the DNA and the suspension of replication and transcription. AIMS: The authors summarized their first experience on second-line topotecan treatment in a prospective non-randomized study. METHOD: Topotecan was given for recurrent epithelial ovarian cancer in the dose of 1.5 mg/m2/d for 5 days repeated in every 3 weeks in a 30-minute infusion intravenously. RESULTS: Twenty five recurrent ovarian cancer patients were treated between March, 1999 and March, 2001. Complete and partial response rates were found 12% and 12%, respectively. Stable disease was observed in 48% of patients for 4-8 courses, then progression continued. In these 3 groups of patients the median progression free interval was shown as 12 weeks. CONCLUSION: When comparing to previous chemotherapies, topotecan treatment failed to show a definitive improvement in the outcome of recurrent ovarian cancer.
UI - 11074389
AU - Lister-Sharp D; McDonagh MS; Khan KS; Kleijnen J
TI - A rapid and systematic review of the effectiveness and cost-effectiveness of the taxanes used in the treatment of advanced breast and ovarian cancer.
SO - Health Technol Assess 2000;4(17):1-113
AD - NHS Centre for Reviews and Dissemination, University of York, York, UK.
SECOND-LINE TREATMENT, PACLITAXEL (MEDIAN PROGRESSION-FREE SURVIVAL): The median progression-free survival in the paclitaxel arm was 3.5 months. This was significantly longer than the mitomycin control arm (1.6 months, p = 0.026). BREAST CANCER - SECOND-LINE TREATMENT, PACLITAXEL (MEDIAN OVERALL SURVIVAL): The median length of overall survival in the paclitaxel arm was 12.7 months, compared with 8.4 months in the mitomycin arm. BREAST CANCER - SECOND-LINE TREATMENT, PACLITAXEL (QUALITY OF LIFE): Quality of life was not reported. BREAST CANCER - SECOND-LINE TREATMENT, PACLITAXEL (ECONOMIC EVALUATION): The only economic evaluation that compared paclitaxel with control (mitomycin) was submitted in confidence and has been removed from this report. Six economic evaluations involved comparisons of paclitaxel and docetaxel, which are given below. BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL: Four randomised controlled Phase III trials were identified: 303 Study, 304 Study, Scand and Bonneterre. A total of 1092 patients were included. One of these was a preliminary report of a study before completion of accrual (Bonneterre). Patients in the 303 Study had previously received chemotherapy involving alkylating agents; those in the other three had received anthracyclines. There were six economic evaluations on docetaxel. BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (QUALITY OF TRIALS): The 303 and 304 Studies were analysed on an intention to treat basis; the Scand trial excluded a single patient. The length of follow-up ranged from 11 months (Scand) to 23 months (303 Study). At least two-thirds of the participants in these trials had died. The Scand study recommended cross-over to alternate treatment on objective signs of disease progression. Patients crossing over in this way were violating the randomisation; however, no details were given concerning whether or not such patients were censored. In the economic analyses, there were no direct comparisons for the estimation of benefits. BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (MEDIAN PROGRESSION-FREE SURVIVAL): The median progression-free survival in the docetaxel arm ranged from 4.75 months (304 Study) to 7 months (Bonneterre). Patients in the docetaxel arms of the 304 and Scand studies had significantly longer progression-free survivals than controls (4.75 months versus 2.75 months, p = 0.001; 6.3 months versus 3 months, p = 0.001). BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (MEDIAN OVERALL SURVIVAL): The median overall survival in the docetaxel arm ranged from 10.4 months (Scand) to 15 months (303 Study). Patients in the docetaxel arms of the 304 Study survived for significantly longer than the mitomycin plus vinblastine arm (11.4 months versus 8.7 months, p = 0.03). BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (QUALITY OF LIFE): Quality of life was evaluated in two of the trials: the 303 and 304 Studies. There were no significant differences between docetaxel and control in either of these trials in terms of global health status, although differences were apparent on some subscales. These did not appear to follow a consistent pattern across the trials. BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (ECONOMIC EVALUATIONS): All six of these involved comparisons of paclitaxel and docetaxel, where the range of cost-utility ratios for incremental quality-adjusted life-years (QALYs) gained was pound 1990-pound 2431. In addition, three analyses compared docetaxel and vinorelbine. The cost-utility ratio for incremental QALYs gained was pound 14,050 in the only one of these carried out in the UK. OVARIAN CANCER - FIRST-LINE TREATMENT, PACLITAXEL: Four randomised controlled Phase III trials were identified: EORTC, TITGANZ, E1193 and CA139-278. (ABSTRACT TRUNCATED)
UI - 11838308
AU - Mendilcioglu I; Zorlu CG; Trak B; Ciftci C; Akinci Z
TI - Laparoscopic management of adnexal masses. Safety and effectiveness.
SO - J Reprod Med 2002 Jan;47(1):36-40
AD - Department of Obstetrics and Gynecology, Akdeniz University School of Medicine, Antalya, Turkey. email@example.com
OBJECTIVE: To evaluate the effectiveness and safety of the laparoscopic approach to adnexal masses. STUDY DESIGN: Sixty-one patients who underwent laparoscopic intervention due to various types of adnexal assessed retrospectively. Patients with strong evidence of advanced ovarian cancer, such as large masses, ascites or omental cake, were excluded. Frozen section was performed intraoperatively, if indicated. In cases of malignancy, laparotomy was performed. RESULTS: Mean operation time was 67.2 minutes; average hospital stay was 1.2 days. Cyst enucleation was performed in 34% of patients. Two of 61 patients were diagnosed as having malignant disease and converted to laparotomy. Chemical peritonitis was encountered after dermoid cyst removal due to spillage of contents in spite of using an endobag and irrigating copiously with saline. No other complications were seen. CONCLUSION: Laparoscopy is a safe approach to adnexal masses and may decrease the rate of unnecessary laparotomies for benign cysts, which give no suspicious ultrasonographic signs.
UI - 11937443
AU - Riedinger JM; Eche N; Basuyau JP; Daver A; Touzery C; Mayer F; Coudert
TI - B; Fargeot P; Chauffert B; de Gislain C; Zanetta S [Interpretation of the CA125 kinetics during first line chemotherapy of the ovarian cancer: methodological aspects and characteristic profiles]
SO - Ann Biol Clin (Paris) 2002 Mar-Apr;60(2):183-91
AD - Laboratoire de biologie medicale, Centre Georges-Francois-Leclerc, 1, rue du Professeur-Marion, 21079 Dijon cedex.
Mathematical analysis of CA125 kinetics during first line chemotherapy allows calculation of various biologic parameters which are powerful indicators of the therapeutic efficiency. The purpose of this study is to present an original method of interpretation of CA125 kinetics based on both CA125 profile and its half-life value. The first part of this study reviews the practical modalities of CA125 kinetics analysis, the methods of calculation of the biologic parameters as well as the guidelines of interpretation. The second part of this work is dedicated to the presentation of CA125 profile characteristics in responders to chemotherapy, partially or totally nonresponders to chemotherapy, tumoral growth under treatment and tumor lysis syndrome.
UI - 12051874
AU - Duska LR; Garrett A; Eltabbakh GH; Oliva E; Penson R; Fuller AF
TI - Paclitaxel and platinum chemotherapy for malignant mixed mullerian tumors of the ovary.
SO - Gynecol Oncol 2002 Jun;85(3):459-63
AD - Vincent Gynecology Service, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. firstname.lastname@example.org
OBJECTIVE: Malignant mixed mullerian tumor (MMMT) of the ovary is a rare tumor with a dismal prognosis. The most effective therapy is unknown. The current study was undertaken to characterize a group of patients treated as if they had aggressive epithelial ovarian tumors, with cytoreductive surgery and combination paclitaxel/platinum chemotherapy. METHODS: Retrospective analysis of data obtained from tumor registry and hospital records of cases of malignant mixed mullerian tumor between January 1, 1992 and January 1, 2000 treated at the Massachusetts General Hospital, Brigham and Women's Hospital, and University of Vermont was performed. Only patients treated with combination paclitaxel and platinum therapy were included in the analysis. Data were collected regarding cytoreduction, response to chemotherapy, disease-free interval, and survival. RESULTS: Fifty-five patients were identified with MMMT. Twenty-eight patients with a clearly ovarian primary had received treatment with combination paclitaxel and platinum. Paclitaxel and carboplatin was given as second-line therapy in 2 patients who had chemoresponsive but incurable disease; the remaining patients were treated with paclitaxel and platinum therapy as first-line therapy. These 28 patients had a median (range) age of 66 (46-84 years) and stage was I in 2 patients, II in 3, III in 18, and IV in 5. Treatment was generally well tolerated. Sixteen patients of 26 treated with paclitaxel and platinum as first-line therapy achieved a complete clinical response (55%) and 6 patients achieved partial response for a total response rate of 72%. Optimal cytoreduction was associated with increased time to recurrence (P = 0.001) but not with survival. Overall median survival for the 28 patients is 27.1 months. CONCLUSION: Although treatment fails many patients, a minority of patients with MMMT in this highly selected population do unexpectedly well. An aggressive approach with surgery and combination paclitaxel-platinum chemotherapy appears to offer very effective therapy.
UI - 12051875
AU - Bailey HH; Levy D; Harris LS; Schink JC; Foss F; Beatty P; Wadler S
TI - A phase II trial of daily perillyl alcohol in patients with advanced ovarian cancer: Eastern Cooperative Oncology Group Study E2E96.
SO - Gynecol Oncol 2002 Jun;85(3):464-8
AD - University of Wisconsin-Madison, Madison, Wisconsin 53792, USA. email@example.com
OBJECTIVE: This was a phase II study of perillyl alcohol in the treatment of advanced ovarian cancer. The primary endpoint was to evaluate the 6-month progression-free rate of perillyl alcohol as compared with historic controls. Secondary objectives were to evaluate the objective response rate, time to progression and survival, dropout rate, and number of cycles administered; define the qualitative nature of acute and chronic toxicities; and evaluate the effect of perillyl alcohol on triglycerides and total, HDL, and LDL cholesterol levels. Methods. Women who had received prior platinum-based therapy and had residual or recurrent disease were eligible. Perillyl alcohol was administered orally, four times daily, at a dose of 1200 mg/m(2). This was repeated until disease progression or unacceptable toxicity was experienced. RESULTS: The 6-month progression-free rate was 17%. None of the patients achieved a complete or partial response. The median progression-free survival was 1.7 months. The median overall survival was 9.1 months. Compliance was greater than 90% but gastrointestinal toxicity (grade 1-2 nausea, satiety, eructation in 70%) and fatigue (grade 1-2 in 40%) were common and limited the ability to escalate the dose from 1200 to 1500 mg/m(2). CONCLUSION: Perillyl alcohol administered at this dose and formulation did not exhibit signs of extending the time-to-progression in patients with advanced ovarian carcinoma.
UI - 12051879
AU - Anupol N; Ghamande S; Odunsi K; Driscoll D; Lele S
TI - Evaluation of prognostic factors and treatment modalities in ovarian cancer patients with brain metastases.
SO - Gynecol Oncol 2002 Jun;85(3):487-92
AD - Division of Gynecologic Oncology, Department of Surgery, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, New York 14263, USA.
OBJECTIVE: The objective of this study is to evaluate the impact of different clinical variables and treatment modalities on survival in patients with brain metastases from ovarian carcinoma. METHODS: Methods included: (1) retrospective chart review of all patients with ovarian cancer and brain metastases from 1986 to 2000 at Roswell Park Cancer Institute and (2) Medline search was performed to extract data from all published reports with three or more cases of ovarian cancer with brain metastases. Cox regression analysis, Kaplan-Meier test, and log rank test were used to calculate survival and compare the impacts of clinical variables and treatment modalities. RESULTS: Fifteen patients with brain metastases out of 1042 women with ovarian carcinoma were identified from our institution, an incidence of 1.4%. The median time from initial diagnosis to detection of brain metastases was 22 months. Patients who were not treated after brain metastasis had a median survival of 0.5 month versus 6 months with therapy. In the subgroup of patients treated with a combination of radiation, surgery, and chemotherapy, the median survival was 22 months. Literature analysis combined with our data generated 124 patients. The only clinically significant variable impacting survival was the presence or absence of additional distant recurrence with median survivals of 3 and 8 months, respectively (P = 0.005). Among patients who received treatment, the combination of radiation and surgery with or without chemotherapy appears to be beneficial, with a median survival of 20 months (P < 0.001). CONCLUSION: Patients with brain metastases from ovarian cancer without any evidence of disease in other sites appear to benefit from aggressive combined treatment with external radiation and surgery with or without chemotherapy with a median survival of 20 months.
UI - 12082646
AU - Harper P
TI - Current clinical practices for ovarian cancers.
SO - Semin Oncol 2002 Jun;29(3 Suppl 8):3-6
AD - Medical Oncology Department, Guy's Hospital, London, UK.
Ovarian cancer is one of the most aggressive gynecologic cancers. It shows its symptoms late and is consequently often diagnosed at an advanced stage. The search for a more effective chemotherapy regimen, therefore, is of great importance. Since 1996, the combination of cisplatin and paclitaxel has been proven to prolong survival in comparison with older regimens containing cisplatin and cyclophosphamide. In addition, the introduction of carboplatin in combination with paclitaxel showed similar efficacy but preferable toxicity profiles when compared with cisplatin in combination with paclitaxel. Representative studies evaluating paclitaxel combination therapies as well as new trends in the treatment of ovarian cancer are summarized in this article. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11828945
AU - Kuzuya K; Ishikawa H; Nakanishi T; Kikkawa F; Nawa A; Fujimura H; Iwase
TI - A; Arii Y; Kawai M; Hattori S; Sakakibara K; Sasayama E; Furuhashi Y; Suzuki T; Mizutani S; Tokai Gynecologic Oncology Group Optimal doses of paclitaxel and carboplatin combination chemotherapy for ovarian cancer: a phase I modified continual reassessment method study.
SO - Int J Clin Oncol 2001 Dec;6(6):271-8
AD - Department of Gynecology, Aichi Cancer Center Hospital, 1-1 Kanoko-den, Chikusa-ku, Nagoya 464-8681, Japan. firstname.lastname@example.org
BACKGROUND: A multicenter, phase I study of combination therapy with paclitaxel and carboplatin for epithelial ovarian cancer was conducted to determine the safety and recommended dosages for Japanese women. METHODS: Paclitaxel was administered intravenously over a 3-h period, followed by carboplatin administered intravenously over a 1.5-h period. A modified continual reassessment method (mCRM) was used in two treatment arms to establish the maximum tolerated dose (MTD) and recommended doses of the combination. In group A, the dose of paclitaxel (175 mg/m2) was constant and the dose of carboplatin was increased from 4 to 7 in terms of the target area under the plasma concentration-versus-time curve (AUC). In group B, the dose of carboplatin was constant (AUC 6) and paclitaxel was administered at two dose levels (160 and 175 mg/m2). In both groups, the carboplatin dose was limited to a maximum of 800 mg/body for each administration. RESULTS: Because the calculated probability of toxicity was greatest at a dose of paclitaxel 175 mg/m2 and carboplatin AUC 7, this dose was designated the MTD in group A. Based on this result, treatment in group B was initiated at doses of paclitaxel of 160 mg/m2 and carboplatin AUC 6. While the dose of paclitaxel was escalated to 175 mg/m2, the safety of the combination was confirmed. The most frequent adverse effect was neutropenia, which resolved promptly with the appropriate use of granulocyte-colony stimulating factor (G-CSF). No other severe hematologic or nonhematologic toxicities were observed. CONCLUSIONS: Our study demonstrated that the recommended dose for this combination regimen should be paclitaxel 175 mg/m2 plus carboplatin AUC 6 (maximum dose, 800 mg/body).
UI - 12057050
AU - Coukos G; Rubin SC
TI - Early ovarian cancer.
SO - Curr Treat Options Oncol 2000 Jun;1(2):129-37
AD - Division of Gynecologic Oncology, University of Pennsylvania Hospital, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Epithelial ovarian cancer may appear to be confined to the ovaries or pelvis in approximately one-third of patients at exploration, but up to 30% of them will be upstaged following surgical staging. Substage and histotype are the most important prognostic factors that determine the need for adjuvant treatment. Patients with stage Ia or Ib and well-differentiated (other than clear cell) tumors do not require adjuvant treatment. Patients with stage Ia or Ib grade 3 or clear cell histology, as well as any stage Ic and II disease, are at high risk for recurrence. Platinum-based chemotherapy is the mainstay of treatment. Four to six courses are probably adequate, although grade 3 tumors may require further treatment. Preservation of the uterus and the uninvolved contralateral ovary is a viable option in young women with unilateral early disease.
UI - 12057051
AU - Chi DS; Sabbatini P
TI - Advanced ovarian cancer.
SO - Curr Treat Options Oncol 2000 Jun;1(2):139-46
AD - Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
State-of-the-art treatment for advanced ovarian cancer requires a multimodality approach. Aggressive surgical debulking with the goal of optimal cytoreduction is the initial step. After primary cytoreductive surgery, standard treatment for patients with stage III and IV disease is systemic combination chemotherapy consisting of six cycles of paclitaxel and carboplatin. Approximately 70% of patients enter a clinical remission with this approach, yet less than 30% remain disease free. Options following primary therapy include observation or second surgical assessment if no clinical evidence of disease is present. Novel strategies for consolidation are needed. Second-look surgery can be performed safely and effectively laparoscopically, and this is the most accurate means of identifying patients who appear to be clinically free of disease but actually harbor persistent cancer. Although this procedure is an extremely accurate means of identifying these patients, women who have pathologically negative second-look surgery are still at risk for relapse. Patients can receive additional treatment following second-look surgical assessment via the intraperitoneal route if they are pathologically negative or if they have microscopic or small volume disease. Alternatively, additional systemic chemotherapy can be given with non-cross-resistant systemic agents, but no current standard approach for consolidation therapy exists for patients following the completion of primary treatment. Unfortunately, most patients relapse. Multiple agents with similar activity in phase II trials are available to treat patients with advanced recurrent disease. Combination therapy in this setting has not been shown to have significantly superior progression-free or overall survival compared with single agents. The selection of treatment for patients with recurrent disease is currently based on a determination of the treatment-free interval since last treatment, as well as the route, schedule, and expected side effects of the agent.
UI - 12118543
AU - Randall ME; Barrett RJ; Spirtos NM; Chalas E; Homesley HD; Lentz SL;
TI - Hanna M Chemotherapy, early surgical reassessment, and hyperfractionated abdominal radiotherapy in stage III ovarian cancer: results of a gynecologic oncology group study.
SO - Int J Radiat Oncol Biol Phys 1996 Jan 1;34(1):139-47
AD - Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, USA. Marc_randall@iucc.iupui.edu
PURPOSE: To determine outcomes and treatment toxicities in patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma treated with three courses of cisplatin-cyclophosphamide, surgical reassessment (SRA), and hyperfractionated whole abdominal irradiation (WAI). METHODS AND MATERIALS: Forty-two eligible patients entered this prospective Phase II study conducted by the Gynecologic Oncology Group (GOG). Disease characteristics were as follows: age range, 32-76 years (median 58); Stage IIIA (n = 1, 2%), IIIB (n = 2, 5%), IIIC (n = 39, 93%); histology-serous papillary (n = 21, 50%); other (n = 21, 50%); Grade 1 (n = 1, 2%); 2 (n = 14, 33%); 3 (n = 27, 54%); residual disease after initial surgery (present: n = 23, 55%; absent: n = 19, 45%). Five patients progressed while on chemotherapy, could not be effectively cytoreduced, and were not eligible for WAI. Of the remaining 37 patients, 35 received WAI. Surgical reassessment was not performed in five patients. RESULTS: Of 37 patients with known SRA status after chemotherapy, 21 (57%) were grossly positive, 4 (11%) were microscopically positive, and 12 (32%) were negative. Based on measurements recorded following initial laparotomy and surgical reassessment, progression during chemotherapy was noted in 40%, stage disease in 37%, and objective response in 23%. Toxicity during hyperfractionated WAI was limited and reversible. No patient beginning WAI failed to complete or required a significant treatment break. Following WAI, six patients underwent laparotomies for abdominal symptoms; five had recurrent disease. Five additional patients were managed conservatively for small bowel obstruction (SBO) or malabsorption, of whom three subsequently developed recurrence. Twenty-two patients having pelvic boosts were significantly more likely to require management for gastrointestinal morbidity (p = 0.0021). Considering all eligible patients, median disease-free and overall survivals were 18.5 and 39 months, respectively. Considering patients completing chemotherapy and WAI, median disease-free and overall survivals were 24 and 46 months, respectively. CONCLUSIONS: (a) Disease progression occurred within three cycles of cisplatin and cyclophosphamide chemotherapy in 40% of patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma. (b) Following limited chemotherapy, hyper-fractionated WAI was acutely well tolerated. (c) Late radiation-related toxicity was observed in only three patients (8.6%) in the absence of recurrent disease. Late gastrointestinal morbidity was significantly associated with the administration of a pelvic radiotherapy (RT) boost. (d) Short duration chemotherapy followed by SRA and hyperfractionated WAI without a pelvic boost is a promising management option for patients with optimal Stage III ovarian cancer. A Phase III trial will be necessary to determine how this treatment strategy compares with chemotherapy or RT alone in this patient population.
UI - 12112979
AU - Wang J; Li AJ; Karlan BY
TI - Chemotherapy in epithelial ovarian cancer.
SO - Curr Womens Health Rep 2002 Feb;2(1):20-6
AD - Division of Gynecologic Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Boulevard, #160W, Los Angeles, CA 90048, USA.
The management of epithelial ovarian carcinoma can be the most challenging of all the gynecologic malignancies partly because of the paucity of effective screening tools for early-stage disease. Numerous randomized clinical trials identified several cytotoxic agents that are active against epithelial ovarian cancer, but the current standard of care remains optimal surgical cytoreduction followed by platinum and taxane-based chemotherapy. When disease recurs or progresses, alternative chemotherapy regimens often have efficacy, either as a single agent or in combination. While treatment recommendations should be individualized, the disease-free interval after induction chemotherapy is often the most clinically useful parameter to determine selection of second-line therapy. Investigations into novel chemotherapeutic agents and other biologic molecules have led to advances in the therapeutic armamentarium and have improved survival for women with ovarian cancer.
UI - 12112982
AU - Bauknecht T; Meinhold-Heerlein I
TI - Gene therapy of ovarian cancer.
SO - Curr Womens Health Rep 2002 Feb;2(1):39-46
AD - Department of Obstetrics and Gynecology, University of Bonn Medical School, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. email@example.com
For the treatment of ovarian cancer, gene therapy is increasingly viewed as the fourth therapeutic concept (in addition to surgery, chemotherapy, and irradiation). Many approaches that use viral and nonviral delivery systems have been employed to introduce genes into tumor cells, thus changing their malignant phenotype. The development of tissue-specific promoters has enhanced the specificity of adenoviral transduction, the most commonly used transfer method. Phase I clinical trials (targeting p53, BRCA1, Her2/neu, Bcl-2, MDR, EIA, and HSV-TK genes) have been performed to test the relative safety of different strategies. Further studies are needed to evaluate the effectiveness of these treatments. New studies must evaluate gene therapy alone and in combination with cytostatic regimens because preclinical studies have shown the chemosensitizing effects of several target genes. The increasing knowledge about the genetic background of ovarian cancer will provide many targets for novel gene therapy approaches.
UI - 12113097
AU - Anonymous
TI - Novuspharma announces preliminary results of phase II trials for BBR 3464.
SO - Expert Rev Anticancer Ther 2001 Oct;1(3):325-6
UI - 12079297
AU - Trimble CL; Kosary C; Trimble EL
TI - Long-term survival and patterns of care in women with ovarian tumors of low malignant potential.
SO - Gynecol Oncol 2002 Jul;86(1):34-7
AD - Department of Gynecology and Obstetrics, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
OBJECTIVES: The objectives of this study were to ascertain long-term survival and patterns of care among women diagnosed with ovarian tumors of low malignant potential (LMP) in a population-based data set. METHODS: Using the NCI's Surveillance, Epidemiology, and End Results (SEER) database, we identified 2818 women diagnosed with ovarian tumors of low malignant potential between 1988 and 1997. RESULTS: By FIGO stage, 10-year relative survival was as follows: stage I, 99%; stage II, 98%; stage III, 96%; and stage IV 77%. One-quarter of women with stage I disease underwent partial or unilateral oophorectomy only, while women with more advanced disease commonly underwent omentectomy, unilateral or bilateral oophorectomy, and hysterectomy. Adjuvant chemotherapy was given to about 30% of women with stage III and IV disease. Radiation therapy was rarely used. We observed no significant changes in primary surgery or adjuvant treatment over time. CONCLUSIONS: The diagnosis of an ovarian tumor of LMP conveys a relatively benign prognosis. Conservative surgery should be considered in younger women with early-stage disease. There are insufficient data to support a role for adjuvant chemotherapy for women with advanced disease. (c) 2002 Elsevier Science (USA).
UI - 12079301
AU - Saygili U; Guclu S; Uslu T; Erten O; Demir N; Onvural A
TI - Can serum CA-125 levels predict the optimal primary cytoreduction in patients with advanced ovarian carcinoma?
SO - Gynecol Oncol 2002 Jul;86(1):57-61
AD - Department of Obstetrics and Gynecology, Dokuz Eylul University School of Medicine, Izmir, Turkey. Saygiliu@hotmail.com
OBJECTIVE: The aim of this study was to investigate the predictive value of serum CA-125 levels to ability of optimal primary cytoreduction in patients with advanced epithelial ovarian carcinoma. METHODS: Preoperative serum CA-125 levels were determined by a commercial enzyme immunoassay kit in a series of 92 patients with stage IIIC epithelial ovarian carcinoma. The abilities of various cutoff value of CA-125 to predict suboptimal cytoreductive surgery were determined. A receiver operating characteristic curve was used to find the most clinically useful CA-125 cutoff value. RESULTS: Optimal cytoreduction was obtained in 48 patients (52%) using the diameter of the largest residual tumor nodule less than 1 cm. Receiver operating characteristic curve showed that the most clinically suitable CA-125 cutoff value was 500 U/ml. Forty-seven patients (51%) had preoperative serum CA-125 levels below 500 U/ml. Of these patients, optimal cytoreductive surgery was performed in 36 (77%). Of the 45 patients with serum CA-125 levels greater than 500 U/ml, optimal cytoreductive surgery was achieved in 12 (27%). True- and false-positive rates were 73 and 23%, respectively. CONCLUSIONS: Although our results showed that preoperative serum CA-125 levels might predict the optimal resectable patients, larger prospective studies are needed to prove its predictivity. Gynecologic oncologists should evaluate the sum of all criteria until more data are available. (c) 2002 Elsevier Science (USA).
UI - 12048682
AU - Jin Z; Guan T; Li S
TI - [Effects of wild-type p53 gene on the chemotherapy sensitivity of ovarian cancer SKOV-3 cells to cisplatin]
SO - Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2002 Jun;19(3):218-20
AD - Department of Obstetrics and Gynecology, the Second Hospital, China Medical University, Shenyang, Liaoning, 110004 P. R. China. firstname.lastname@example.org
OBJECTIVE: To assess the effect of wild-type p53 gene on the chemotherapy sensitivity of ovarian cancer SKOV-3 cells to cisplatin. METHODS: Recombinant eukaryotic expression vector pcDNA3 containing full-length human wild-type p53 cDNA was introduced by lipofectamine-mediated gene transfection into SKOV-3 cultured cells which were acted on by cisplatin of different concentrations. The chemotherapy sensitivity of tumor cells with different-status p53 was observed. RESULTS: The inhibitive rate of formation of clones after p53 cDNA transfection was 56.4% compared with the untransfected one. The formation of clones decreased by 76.2% and 84.1% respectively after being acted on by 0.5 ug/ml cisplatin for 24 hours and 48 hours respectively. The formation of clones decreased by 89.5% and 93.7% respectively after being acted on by 1 ug/ml cisplatin for 24 hours and 48 hours respectively. After the introduction of p53 cDNA, the S phase and the ratio of G(2)/M phase of tumor cells decreased, and the ratio of G(1)/G(0) phase increased. The introduction of p53 gene into cells led to cell cycle arrest in G(1) phase. CONCLUSION: The exogenous introduction of wild-type p53 cDNA into ovarian cancer SKOV-3 cells increased the chemotherapy sensitivity to cisplatin.
UI - 12100804
AU - Cooper BC; Sood AK; Davis CS; Ritchie JM; Sorosky JI; Anderson B; Buller
TI - RE Preoperative CA 125 levels: an independent prognostic factor for epithelial ovarian cancer.
SO - Obstet Gynecol 2002 Jul;100(1):59-64
AD - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, the University of Iowa Hospitals and Clinics, Iowa City 52242, USA.
OBJECTIVE:To estimate the association of preoperative CA 125 levels with outcome in primary ovarian cancer patients.METHODS:One hundred forty-two patients with epithelial ovarian cancer, who had a serum CA 125 level drawn before surgery, were retrospectively evaluated. The relationship of preoperative CA 125 levels and various preoperative and postoperative variables was evaluated. CA 125 levels were determined using a solid-phase immunoassay.RESULTS:The median CA 125 value for all patients was 582 U/mL (range 7-52,930 U/mL). Preoperative CA 125 values did not correlate with increasing age (P =.40), but were found to be significantly associated with serous histology compared with other histology (median CA 125 of 870 versus 334 U/mL, P =.02), high-stage (III/IV) compared with low-stage (median CA 125 of 893 versus 174 U/mL, P <.001), high tumor grade (3) compared with grade 1 or 2 (median CA 125 of 928 versus 323 U/mL, P <.001), and the presence of ascites compared with absence of ascites (median CA 125 of 893 versus 220 U/mL, P <.001). Suboptimal cytoreduction (more than 1 cm residual) was associated with significantly higher CA 125 levels (1067 U/mL) compared with individuals with optimal cytoreduction (399 U/mL, P <.001). Preoperative CA 125 values less than 500 U/mL had a positive predictive value for optimal cytoreduction of 82%, but a poor negative predictive value of 48%. After adjusting for covariates, there was a significant association between CA 125 levels and disease-specific survival. As preoperative CA 125 levels increased, the risk of death increased except at the highest values of CA 125.CONCLUSION:Preoperative CA 125 is an independent risk factor for death due to disease in ovarian cancer, but not a reliable predictor of optimal cytoreduction.
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