National Cancer Institute®
Last Modified: September 1, 2002
UI - 11697814
AU - Distefano M; Ferlini C; De Vincenzo R; Gaggini C; Mancuso S; Scambia G
TI - Antagonistic effect of the combination gemcitabine/topotecan in ovarian cancer cells.
SO - Oncol Res 2000;12(9-10):355-9
AD - Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
The in vitro interaction between the new antimetabolite gemcitabine (GEM) and topotecan (TPT) was analyzed in A2780 ovarian cancer cells. The growth inhibitory effect was assessed after 3 days of drug exposure. GEM and TPT obtained in vitro IC50 values of 2.1 +/- 0.9 and 33.7 +/- 10.2 nM, respectively. The interaction between GEM and TPT was evaluated by exposing cancer cells at increasing doses of GEM (0.1, 1, and 10 nM) and TPT (1, 10, 100, and 1000 nM). Analysis of data about the interaction between GEM and TPT was performed by applying the isobole method. An antagonistic effect was noticed when GEM was combined with TPT in the tested concentration range. DNA analysis was also performed and showed an augmentation of cells blocked in the G2/M phase during TPT exposure, while an increase of blocked cells in the G0/1, phase was observed after GEM treatment. This latter effect was predominant when the two drugs were used in combination. We also investigated the effect of sequential exposure to drugs, pretreating A2780 cells for 24 h with TPT and then for 48 h with GEM, and, conversely, pretreating A2780 cells with GEM for 24 h and thereafter with TPT for 48 h. Both these combined sequential treatments showed an antagonist effect of the drugs' combination. Long-term growth inhibition effect was established by clonogenic assay performed after 10 days of culture after drug treatment. Also these data confirmed the antagonistic effect between GEM and TPT in A2780 ovarian cancer cells.
UI - 12133404
AU - Huang X; Cai S; Fan J; Li Z
TI - [Combined treatment and prognostic analysis of advanced epithelial ovarian carcinoma]
SO - Zhonghua Fu Chan Ke Za Zhi 2002 May;37(5):291-3
AD - Department of Gynecology, Cancer Hospital, Fudan University, Shanghai 200032, China.
OBJECTIVE: To evaluate the effects of combined treatment for advanced epithelial ovarian carcinoma and to analyze its prognostic factors. METHODS: Fifty-three patients treated with a three-step combined therapeutic regimen were defined as research arm. The procedures of the three-step combined treatment were as follows: induction of tumor remission, sequential chemotherapy and adjuvant immunotherapy. Three hundred and eighteen patients with advanced epithelial ovarian carcinoma treated with cytoreductive surgery and systemic chemotherapy were retrospectively classified into control arm. RESULTS: The rates of complete response and partial response in the research arm were significantly differed from those in the control arm (90.6%, 5.7% Vs 70.1%, 5.3%, P < 0.01). The 1-, 2- and 3-year survival rates of the research arm and control arm were 97.7%, 89.1%, 83.6% Vs 71.8%, 44.1%, 29.8%, respectively (P < 0.01). The 1-, 2- and 3-year tumor-free survival rates of the research arm and control arm were 92.6%, 75.0%, 75.0% Vs 60.3%, 37.8%, 28.6%, respectively (P < 0.01). The 1- and 2-year recurrent rates of the patients in research arm were much lower than that in control arm (7.5%, 25.0% Vs 39.7%, 62.2%, P < 0.01). Age, stage, ascites, differential degree, preoperative chemotherapy (intraperitoneal and/or intravenous chemotherapy), postoperative intraperitoneal chemotherapy and systemic chemotherapy were poor prognostic factors. Initially treated in other hospital, bilateral tumors, large residuals (diameter more than 1cm) and postoperative intraperitoneal chemotherapy were poor tumor-free survival prognostic factors. CONCLUSION: Combined therapy including remission induction, consolidation chemotherapy and immunotherapy was able to enhance therapeutic efficacy, decrease the 1- and 2-year recurrent rate and improve the survival of patients with advanced epithelial ovarian carcinoma.
UI - 12015048
AU - Zang R; Zhang Z; Cai S
TI - [Clinical significance of secondary cytoreductive surgery for recurrent advanced ovarian cancer]
SO - Zhonghua Zhong Liu Za Zhi 2002 Mar;24(2):194-6
AD - Department of Gynecological Oncology, Cancer Hospital, Fudan University, Shanghai 200032, China.
OBJECTIVE: To study the role of secondary cytoreductive surgery (SCR) in patients with recurrent advanced epithelial ovarian cancer. METHODS: From Jan. 1986 to Dec. 1997, 60 women with recurrent advanced epithelial ovarian cancer treated with SCR were retrospectively reviewed. Survival curves were computed using the Kaplan-Meier method with differences in survival estimated by log-rank test. Independent prognostic factors were identified by Cox's stepwise regression, and the affecting factors of SCR evaluated by Logistic stepwise regression. RESULTS: Of the 60 patients, 23 (38.3%) were cytoreduced to small macroscopic residual (= 1 cm) and 37 retained larger residual, with an estimated median survival of 19 months and 8 months respectively. Multivariate analysis revealed that residual disease (P = 0.0041) after SCR, as well as refractory ascites (P = 0.0191) and progression-free interval (P = 0.0116), were independent factors of survival. Refractory ascites (relative risk = 20.36, P = 0.0072) and residual disease after primary surgery (relative risk = 5.16, P = 0.0096) were factors affecting SCR. CONCLUSION: Secondary cytoreductive surgery is definitely effective in the treatment of recurrent advanced epithelial ovarian carcinoma, particularly in those who have received primary optimal cytoreduction with a progression-free interval > 12 months and without refractory ascites.
UI - 12082861
AU - Bertelsen K; Knudsen JB
TI - [Ovarian cancer]
SO - Ugeskr Laeger 2002 Jun 3;164(23):3056-9
AD - Onkologisk haematologisk afdeling R, Odense Universitetshospital, DK-5000 Odense C.
UI - 12091073
AU - Mishima M; Samimi G; Kondo A; Lin X; Howell SB
TI - The cellular pharmacology of oxaliplatin resistance.
SO - Eur J Cancer 2002 Jul;38(10):1405-12
AD - Department of Obstetrics and Gynecology, University of Tokyo, Japan.
Oxaliplatin is a third generation platinum compound that differs from cisplatin and carboplatin in having a broader spectrum of antitumour activity. Molecular studies suggest that oxaliplatin adducts are recognised and processed differently than those produced by the earlier generation Pt-containing drugs. We report here studies on the kinetics of the development of oxaliplatin resistance, and the changes in the cellular pharmacology of oxaliplatin that accompany the emergence of the resistant phenotype in five parental human tumour cell lines and their sub-lines selected for acquired oxaliplatin resistance in vitro. During selection, resistance did not substantially increase until after at least six cycles of oxaliplatin treatment. Oxaliplatin demonstrated schedule-dependency with a 1-h exposure being substantially less cytotoxic than a continuous exposure. Whole cell uptake was linear with concentration, but uptake in the resistant cells averaged only 27+/-10 S.D.% of that in the sensitive cells. Pt accumulation in DNA was markedly reduced in four of the five resistant cell lines, but this did not correlate with either IC(50) or total cellular accumulation. Four of the five resistant sub-lines also demonstrated increased tolerance to adducts in DNA that ranged from 3.1 to 7.6-fold. We conclude that development of acquired resistance to oxaliplatin is accompanied by independent defects in both whole cell uptake and in adduct formation.
UI - 12184040
AU - Martin VR
TI - Ovarian cancer.
SO - Semin Oncol Nurs 2002 Aug;18(3):174-83
AD - Ambulatory Care, Fox Chase Cancer Center, 7701 Burholme Ave, Philadelphia, PA 19111, USA.
OBJECTIVES: To review the progress in the management of ovarian cancer in the last decade and future directions. DATA SOURCES: Research studies, review articles, and abstracts. CONCLUSIONS: There is an increased understanding of ovarian cancer biology, the genetic basis for hereditary ovarian cancer, staging and the role of cytoreductive surgery, and more effective chemotherapy, resulting in an increase in the percentage of patients who will live 5 years from the time of diagnosis. IMPLICATIONS FOR NURSING PRACTICE: The nurse can play an invaluable role as the options of treatment are considered and weighed against quality-of-life considerations.
UI - 9402168
AU - Eisenhauer EA; Vermorken JB; van Glabbeke M
TI - Predictors of response to subsequent chemotherapy in platinum pretreated ovarian cancer: a multivariate analysis of 704 patients [seecomments]
SO - Ann Oncol 1997 Oct;8(10):963-8
AD - National Cancer Institute of Canada Clinical Trials Group, Queen's University, Kingston.
BACKGROUND: The probability of response to chemotherapy following platinum based treatment in ovarian cancer has usually been related to the 'platinum-free interval'. However, in a recent European-Canadian trial of paclitaxel, serous histology, tumor bulk, and hemoglobin, but not treatment free interval, were predictors of response. To determine if these observations were unique to this study (or this drug), data from other active agents given as second- or third-line treatment in ovarian cancer were obtained and analyzed. METHODS: In the first part of the study, results of trials in 1185 platinum pretreated ovarian cancer patients were obtained on six agents: paclitaxel, epirubicin, docetaxel, carboplatin, irinotecan, and gemcitabine. Response results according to histology, baseline hemoglobin, tumor size and time from last chemotherapy were determined for each agent and the Cochran-Mantel-Haenszel procedure was used to obtain an overall assessment of significance for each factor. In the second part of the study, individual data from 704 patients in four studies (three agents: paclitaxel, docetaxel and epirubicin) were pooled for univariate and multivariate analysis of factors predictive of response. RESULTS: In the analysis of results of individual agents all factors examined were significant predictors of response: serous histology (P = 0.001), tumor size < or = 5 cm (P = 0.02), normal baseline hemoglobin (P = 0.003), and > or = 6 mo since last treatment (P = 0.001). While these results were interesting, they did not supply definitive answers regarding independent response predictors. Therefore a multifactor analysis was undertaken on the 704 patients for whom individual data were available. Of the 11 factors examined in a univariate analysis, 10 met the criteria for inclusion in a stepwise logistic regression. In the final model only 3 factors remained as significant independent predictors of response: serous histology (P = 0.009), no. disease sites (P = 0.003), and tumor size (P = 0.001). Time from last treatment, when evaluated as a continuous variable, was not in the final model and was highly correlated with tumor size (P = 0.0005). CONCLUSIONS: On the basis of this analysis, we conclude that tumor burden (as assessed by size of the largest lesion and number of disease sites) and histology are factors of importance in response to subsequent chemotherapy in relapsed ovarian cancer. Time from last treatment was correlated with tumor size in this data set and its effect on response was dependent on whether it was examined as a categorical or continuous variable, so we conclude it is not the sole critical factor of biologic importance. We recommend description of these factors in reports of phase II studies, confirmation of these findings in other data sets and further investigation of the mechanism of sensitivity of serous tumors.
UI - 12187169
AU - Warren JL; Harlan LC; Fahey A; Virnig BA; Freeman JL; Klabunde CN;
TI - Cooper GS; Knopf KB Utility of the SEER-Medicare data to identify chemotherapy use.
SO - Med Care 2002 Aug;40(8 Suppl):IV-55-61
AD - Applied Research Program, National Cancer Institute, Bethesda, Maryland 20892-7344, USA.firstname.lastname@example.org
BACKGROUND: Medicare claims include codes for chemotherapy administration and specific drugs given, and researchers are increasingly using these data to measure the use of chemotherapy. However, the validity and completeness of these data as a source of information has not been established. OBJECTIVES: This analysis is intended to assess the utility of the Medicare claims to capture chemotherapy use. METHODS: Persons with breast, colorectal, and ovarian cancer were identified from the linked SEER-Medicare data. Their Medicare claims were reviewed to determine if there were any bills for chemotherapy, and if so, if there were claims for specific agents. This information was compared with data on the first course of treatment obtained from hospitals and treating physicians by the SEER registries through an NCI-supported Patterns of Care Studies (POC). Agreement was measured using kappa statistics. The sensitivity of the Medicare claims to capture chemotherapy, as reported from the POC data, was also measured. An additional comparison assessed the agreement between the two data sources concerning which specific drugs had been given. RESULTS: For all of the cancers, there was a high level of agreement between the Medicare claims and the POC data regarding whether or not the patient had received chemotherapy (kappa >or=0.73). The sensitivity of the Medicare data to determine if a person had received chemotherapy was high (>or=88%). In cases where the Medicare claim included a code for a specific drug, there high agreement between Medicare and POC about the specific drug given in breast and colorectal cancers, although the agreement was lower for ovarian cancers. The sensitivity of the Medicare claims to identify specific agents varies by cancer type. CONCLUSIONS: The Medicare claims can be used to identify which persons are receiving chemotherapy. The utility of Medicare data to measure treatment with specific agents varies by cancer type and specific agent. For some cancers, it is possible to use these claims to assess use of specific drugs, while for other drugs the data are limited.
UI - 12214460
AU - Isonishi S
TI - [Latest information in the diagnoses of ovarian carcinoma]
SO - Gan To Kagaku Ryoho 2002 Aug;29(8):1351-7
AD - Dept. of Obstetrics and Gynecology, Jikei University School of Medicine.
Despite improvements in median and overall survival from a combination of improved operation techniques and chemotherapy with platinum-compounds and paclitaxel, long-term survival rates for patients with epithelial ovarian carcinoma remain disappointing, and ongoing efforts are aimed at developing more effective primary therapies. In early ovarian carcinoma, conservative management is used to denote surgery that preserves reproductive potential without compromising curability. With some exceptions, such a strategy may be applicable for women younger than 40, who wish to bear children. A major dilemma facing gynecologic oncologists is to determine whether the accurate staging laparotomy is needed for apparent low-risk stage I ovarian carcinoma and how many cycles of chemotherapy will be needed for high-risk stage I ovarian carcinoma. In advanced ovarian carcinoma, main objectives of salvage therapy include: a improvement in quality of life and symptoms; b. tumor load reduction and survival advantage; c. evaluation of potentially active new drugs to be included in first-line treatment. We need to evaluate the potential benefit on survival of systematic pelvic and para-aortic lymphadenectomy during primary or secondary cytoreductive surgery in patients with advanced ovarian carcinoma. Paclitaxel/cisplatin is considered to be the international standard treatment based on the data of GOG 111 trial showing that paclitaxel/cisplatin has provided a survival benefit better than that of cyclophosphamide/cisplatin. This choice of standard therapy might, however, be questioned based on the results of the largest randomised study, ICON3. There were no statistically significant differences in progression-free or overall survival among paclitaxel/carboplatin and carboplatin only or a platinum combination (cyclophosphamide/doxorubicin/cisplatin). The best selection for adjuvant chemotherapy is still controversial and a large number of studies are now ongoing.
UI - 12214461
AU - Sugiyama T; Ohta S; Tomonari R; Kamura T
TI - [Treatment of malignant ovarian germ cell tumor and sex cord tumors]
SO - Gan To Kagaku Ryoho 2002 Aug;29(8):1358-62
AD - Department of Obstetrics and Gynecology, Iwate Medical University, 19-1 Uchimaru, Morioka, 020-8505, Japan.
We outline chemotherapy mainly for malignant ovarian germ cell and sex-cord tumors, based on studies in the literature and our own clinical experiences. With both tumors, PEB treatment is standard adjuvant chemotherapy. With regard to the number of dosage courses, 4 courses are regarded as tolerable after incomplete reduction, and 3 courses as adjuvant treatment after complete extraction. This chemotherapy is effective for preservation of fertility in young patients with malignant ovarian germ cell tumor. In both tumors, some cases show chemotherapy resistance. An effective second-line treatment strategy using a new anticancer agent needs to be established for such cases in the future.
UI - 12168878
AU - Takano M; Kikuchi Y; Kita T; Suzuki M; Ohwada M; Yamamoto T; Yamamoto K;
TI - Inoue H; Shimizu K Phase I and pharmacological study of single paclitaxel administered weekly for heavily pre-treated patients with epithelial ovarian cancer.
SO - Anticancer Res 2002 May-Jun;22(3):1833-8
AD - Department of Obstetrics and Gynecology, National Defense Medical College, Saitama, Japan.
We have reported that paclitaxel results in cisplatin sensitization in cisplatin-resistant ovarian cancer cell lines in vitro and in nude mice. The purpose of this trial was to determine the maximum tolerated dose and recommend phase II dose of weekly single agent paclitaxel for outpatients with recurrent or persistent epithelial ovarian carcinoma (REOC), with standard chemotherapy containing platinum in the initial setting. Patients with REOC were eligible for this protocol regardless of the number and kind of previous chemotherapy regimens. The starting dose was paclitaxel 70 mg/m2/week in 1-hour infusion, 3 weeks on, 1 off and repeated at least twice. This dose was increased by 10 mg per step to 100 mg/m2/week. Three patients were accrued to each dose cohort. Three new patients were to be entered at escalation doses unless dose-limiting toxicities (DLT) occurred, defined as grade 4 hematological or grade 3/4 non-hematological toxicities. If 1 out of 3 patients developed DLT, 3 additional patients were entered at the same dose level. Sixteen patients were accrued. All the patients had received at least one prior platinum-containing regimen (1 regimen 14 cases, 2 regimens 1 case, 3 regimens 1 case). At the level I dose of 70 mg/m2/week no hematological or non-hematological toxicity more than grade 2 was observed. At the level II dose of 80 mg/m2/week, 1 patient had grade 4 non-hematological toxicity, showing difficulty-walking. Three new additional patients were treated with the same dose. Except for this patient, 1 had grade 3 leukopenia and grade 4 neutropenia, but these toxicities were overcome within 3 days without support of granulocyte-colony stimulating factor (G-CSF). At the level III dose, 90 mg/m2/week, 1 of 3 patients showed grade 4 leukopenia and 2 had grade 4 neutropenia, requiring support by G-CSF. Similarly, when using 100 mg/m2/week of paclitaxel, 2 out of 4 patients had more than grade 3 hematological toxicity. However, at levels II or IV, no non-hematological toxicity exceeding grade 2 was observed. Even if the weekly single paclitaxel was repeated, the toxicity did not seem to accumulate. According to dose-escalation, use of G-CSF and treatment delay were increased. The use of G-CSF was significantly (p<0.05) increased between levels I, II, III and IV. Although treatment with 90 or 100 mg/m2/week, at 3 weeks on, 1 off was tolerable and safe with support of G-CSF, these doses cannot be recommended for out-patients because of treatment delay. In this phase I trial, 80 mg/m2/week of paclitaxel was recommended as the phase II dose for outpatients.
UI - 12009393
AU - Hasenburg A; Fischer DC; Tong XW; Rojas-Martinez A; Kaufman RH; Ramzy I;
TI - Kohlberger P; Orlowska-Volk M; Aguilar-Cordova E; Kieback DG Adenovirus-mediated thymidine kinase gene therapy for recurrent ovarian cancer: expression of coxsackie-adenovirus receptor and integrins alphavbeta3 and alphavbeta5.
SO - J Soc Gynecol Investig 2002 May-Jun;9(3):174-80
AD - Department of Obstetrics and Gynecology, University Medical Center, Hugstetter Strasse 55, 79106 Freiburg/Brsg., Germany. email@example.com
OBJECTIVE: Ten patients with recurrent ovarian cancer received a combined treatment of optimal tumor debulking, adenovirus-mediated herpes simplex virus thymidine kinase gene therapy (GT), and systemic application of acyclovir or valacyclovir and topotecan. Biopsies were taken at the time of secondary debulking about 1 month after the application of GT and chemotherapy and were analyzed for expression of coxsackie-adenovirus receptor (CAR) and integrins alphavbeta3 and alphavbeta5 with respect to treatment response. METHODS: Treatment modalities and study design have been described recently. Immunohistochemistry was used to visualize expression of CAR and integrins alphavbeta3 and alphavbeta5 in tumor samples taken before and after application of GT. RESULTS: Before GT six of ten patients presented with CAR-positive and four with CAR-negative tumors. After GT all tumors showed CAR expression. Integrin alphavbeta3 was found in all tumors before and after GT. Expression of integrin alphavbeta5 was seen in eight of ten tumor samples before GT and in all samples after GT. CONCLUSION: Despite the importance of CAR and integrin expression for successful adenovirus internalization, other cell surface receptors might be involved in this process. It is too early to decide whether expressions of CAR and integrin alphavbeta3/alphavbeta5 on tumor cells are appropriate additional inclusion criteria for the enrollment of patients in GT trials. Further research is necessary to evaluate the effect of GT plus chemotherapy on CAR and integrin expression.
UI - 12210444
AU - Stern JW; Bunin N
TI - Prospective study of carboplatin-based chemotherapy for pediatric germ cell tumors.
SO - Med Pediatr Oncol 2002 Sep;39(3):163-7
AD - Division of Oncology, The Children's Hospital of Philadelphia and The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. firstname.lastname@example.org
BACKGROUND: Survival of pediatric patients with malignant germ cell tumors has improved dramatically with the use of cisplatin-based chemotherapy, though patients are at high risk of significant long-term complications. In a prospective study, carboplatin was substituted for cisplatin in an attempt to minimize nephro- and oto-toxicities, while achieving excellent disease-free survival. PROCEDURE: All consecutive patients with malignant germ cell tumors at The Children's Hospital of Philadelphia were treated between 1989 and 1998. After pathologic confirmation of disease and pretreatment evaluation of pulmonary, renal, and otologic function, patients received etoposide 150 mg/m(2) days 1, 2, 3; carboplatin 600 mg/m(2) day 2; and bleomycin 10 mg/m(2) day 3 for at least four courses. RESULTS: Twenty-three patients were entered for study, and were available for evaluation. All patients achieved either a complete or partial remission following therapy with surgery and chemotherapy. With a median of 58 months of follow-up, overall survival is 91% and event-free survival is 87%. Therapy was given as an outpatient, and well tolerated, with 20 admissions for fever and neutropenia. Ototoxicity and nephrotoxicity, when evaluated, have been extremely limited. Three patients, all with stage III disease, have relapsed; one of these remains alive and disease free. CONCLUSIONS: Carboplatin can successfully substitute for cisplatin during the treatment of pediatric germ cell tumors without sacrificing response or survival. Long-term effects, especially nephrotoxicity and ototoxicity, were rare or mild among the small number of patients evaluated. Carboplatin appears to be a safe and efficacious alternative in the treatment of germ cell tumors, and should be considered as primary therapy for pediatric patients. Copyright 2002 Wiley-Liss, Inc.
UI - 12187066
AU - Sugiyama T; Yakushiji M; Kamura T; Ikeda M; Umesaki N; Hasegawa K;
TI - Ishikawa M; Saji F; Hiura M; Takahashi T; Sato S; Ochiai K; Kikkawa F; Takeuchi S; Ohashi Y; Noda K; Japan CPT-11 Study Group Irinotecan (CPT-11) and cisplatin as first-line chemotherapy for advanced ovarian cancer.
SO - Oncology 2002;63(1):16-22
AD - Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume City, Japan. email@example.com
OBJECTIVE: To evaluate the efficacy and toxicity of a combination of irinotecan (CPT-11) and cisplatin as first-line chemotherapy in advanced ovarian cancer. METHODS: Twenty-six patients with previously untreated advanced epithelial ovarian cancer were enrolled in this study. CPT-11 60 mg/m(2) was administered intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m(2) on day 1. Cycles were repeated every 28 days for at least two cycles. The median patient age was 55 years (range, 37-75), and the median performance status was 1. RESULTS: Objective responses were recorded in 19 of 25 eligible patients (76%; 95% confidence interval, 55-91%). Complete responses were obtained in 2 patients (8%), and partial response in 17 patients (68%). Stable disease was recorded in 2 patients (8%) and progressive disease in 2 (8%). The median time to response was 62 days (range, 28-234 days). The median survival time for all 25 patients was 30.9+ months (range, 4.1-60.0+ months). The major toxic effects were leukopenia, neutropenia, and diarrhea. Grade 3 or 4 leukopenia, neutropenia, and diarrhea occurred in 17 (68%), 20 (83.3%), and 5 patients (20%), respectively. Thrombocytopenia was less common. No treatment-related deaths occurred. CONCLUSION: The combination of CPT-11 and cisplatin showed significant activity in chemotherapy-naive patients with advanced ovarian cancer. Neutropenia was the dose-limiting adverse effect, whereas diarrhea was mainly mild to moderate. Copyright 2002 S. Karger AG, Basel
UI - 12060445
AU - Fujiwara K; Suzuki S; Yoden E; Ishikawa H; Imajo Y; Kohno I
TI - Local radiation therapy for localized relapsed or refractory ovarian cancer patients with or without symptoms after chemotherapy.
SO - Int J Gynecol Cancer 2002 May-Jun;12(3):250-6
AD - Department of Obstetrics and Gynecology, Kawasaki Medical School, 577 Matsushima, Kurashiki-City 701-0192, Japan. firstname.lastname@example.org
The purpose of this paper is to prospectively evaluate the effects of local radiation therapy upon localized ovarian cancer following chemotherapy. Patients with objective relapses or refractory disease but with localized epithelial ovarian cancers and who had undergone at least one regimen of chemotherapy were enrolled in this study. External irradiation was performed on all patients. Twenty patients, with a mean age of 53.8 +/- 10.3 y, were enrolled in this study. The median number of previous chemotherapies was 2. The interval between previous chemotherapy and radiation therapy was 4.5 months. The maximum diameter of the lesions was 3.6 +/- 1.8 cm. The irradiation dose was 52.3 +/- 8.3 Gy. Neither hematologic nor intestinal toxicity >grade 3 was observed. Forty-four disease sites, including the lymph nodes, vaginal cuff, pelvis, abdomen, subcutaneous regions, and the brain were irradiated. Thirty of these sites were symptom-free before irradiation. In patients with symptoms, the symptomatic relief was obtained in approximately 50% of patients. Smaller lesions (P = 0.024) and lymph nodes (P = 0.042) demonstrated better responses than larger lesions or other sites, respectively. Regression rates correlated with longer survivals (P = 0.0195) after radiation therapy. Survival was significantly better when radiation therapy was given before patients had symptoms (P = 0.001). Survival was also better in patients with lymph node disease only (P = 0.0069). We conclude that local radiation therapy may be one of the treatment options for relapsed or refractory but localized ovarian cancer, particularly when the tumor is small and/or located in the lymph nodes, even when patients had no symptoms.
UI - 12133408
AU - Yuan B; Mi R
TI - [Antisense oligodeoxynucleotides of human telomerse catalytic sub-unit inhibits telomerase activity and proliferation in SKOV3 and COC1]
SO - Zhonghua Fu Chan Ke Za Zhi 2002 Apr;37(4):198-201
AD - Department of Obstetrics and Gynecology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
OBJECTIVE: To study the effects of antisense oligodeoxynucleotides (ODN) of hEST2 (AODN) on telomerase activity and proliferation in ovarian cancer cell lines SKOV3 and COC1. METHODS: Antisense and sense human telomerse catalytic sub-unit (hEST2) phosphorothioate (SODN) and random ODN were designed, synthesized and transfected into SKOV3 and COC1 cells by lipofectamine. The expression of hEST2 mRNA and telomerase activity in SKOV3 and COC1 were tested by reverse transcription-polymerase chain reaction and telomeric repeat amplification protocol before and after transfection. The proliferation and growth in SKOV3 and COC1 were also investigated by methyl thiazolyl tetrazolium and growth curve before and after transfection. RESULTS: AODN could down-regulate the expression of hEST2 mRNA, inhibit telomerase activity and proliferation of ovarian cell lines. The efficiency depends on dose and period of administration. At 48 h, 30 micromol/L AODN had the highest activity. The expression of hEST2 mRNA were declined 54.6% and 44.6% in SKOV3 and COC1 respectively. And also the inhibition of telomerase activity were 47.9% and 42.7% respectively in the two cell lines. CONCLUSIONS: AODN of hEST2 clearly inhibited the proliferation of ovarian cancer cell lines. hEST2 may thus be a new target of gene therapy in ovarian carcinoma.
UI - 12133409
AU - Wang C; Hu F; Lu Y; Wang S; Ma D
TI - [Effects of RelA antisense oligonucleotide on apoptosis of ovarian cancer cells COC1]
SO - Zhonghua Fu Chan Ke Za Zhi 2002 Apr;37(4):202-4
AD - Department of Obstetrics and Gynecology, Tongji Hospital of Tongji Medical College, Huazhong Science and Technology University, Wuhan, 430030, China.
OBJECTIVE: To evaluate the effects of RelA antisense oligonucleotide on apoptosis of ovarian cancer cells. METHODS: COC1 cell line was treated with RelA antisense oligonucleotide combining with tumor necrosis factor (TNF)-alpha or paclitaxel at appropriate concentrations and duration. The apoptosis and RelA activation of ovarian cancer line COC1 cell were measured by indirect immunofluorescence, Western blot, flow cytometric analysis, DNA ladder assay. RESULTS: The apoptosis increased obviously in COC1 rells if treated by RelA antisense oligonucleotide combining with paclitaxel 50 micromol/L than paclitaxel 50 micromol/L only (27.4 +/- 0.5)% vs (12.3 +/- 0.6)% (P < 0.01), when treated 12 hs; (31.7 +/- 0.3)% vs (13.0 +/- 0.5)% (P < 0.01) when treated 24 hs. The apoptosis was also increased obviously in COC1 cells if treated by RelA antisense oligonucleotide combining with TNF-alpha 50 microgram/L than TNF-alpha 50 microgram/L alone. (30.8 +/- 0.3)% vs (13.2 +/- 0.4)% (P < 0.01). CONCLUSION: RelA antisense oligonucleotide may induce apoptosis susceptibility of COC1 cells to TNF-alpha or paclitaxel.
UI - 12168915
AU - Ness RB; Wisniewski SR; Eng H; Christopherson W
TI - Cell viability assay for drug testing in ovarian cancer: in vitro kill versus clinical response.
SO - Anticancer Res 2002 Mar-Apr;22(2B):1145-9
AD - Graduate School of Public Health, University of Pittsburgh, PA 15261, USA.
Several methods have been and are in use for assessing the in vitro sensitivity and resistance of an individual woman's tumor cells. We report the predictive accuracy of an optimized chemoresponsiveness test. PATIENTS AND METHODS: In a retrospective chart review of 18 women with late stage, papillary serous ovarian cancer undergoing 21 episodes of chemotherapy, we assessed the correlation between the results of this test, the ChemoFx Assays, and clinical response. RESULTS: The positive predictive value of the ChemoFx Assay was 63.6% and the negative predictive value was 100%. Survival curves among women with good vs. poor response on the chemoresponse test showed an early, albeit non-significant survival advantage among women whose tumors tested sensitive to the chemotherapeutic regimens used. CONCLUSION: This study suggests that optimized chemoresponse assays may be beneficial in selecting specific chemotherapy regimens for women with ovarian cancer.
UI - 12168916
AU - Vuento MH; Salmi TA; Remes KJ; Grenman SE
TI - Hematological toxicity of salvage treatment after high-dose chemotherapy and conventional chemotherapy of ovarian cancer.
SO - Anticancer Res 2002 Mar-Apr;22(2B):1151-5
AD - Departments of Obstetrics and Gynecology, Turku University Central Hospital, Finland.
BACKGROUND: To compare the toxicity of salvage chemotherapy (CT) given for recurrent or progressive ovarian cancer (OC) after either high-dose chemotherapy (HDC) or conventional CT. PATIENTS AND METHODS: HDC supported by autologous stem cell transplantation was given to ten OC patients. Seven of them were treated with salvage CT for recurrent disease and were included in this study (Group A). Seven patients with recurrent OC treated primarily with conventional CT (Group B) were matched for age (+/- 3 years), stage and histology. The hematological toxicity of treatment was graded according to the WHO criteria. RESULTS: During salvage CT, grade 3-4 neutropenia was seen in nine out of 81 courses (11.1%) in Group A and in six out of 85 courses (7.1%) in Group B (p <0.1). The use of G-CSF was more common in Group A than in Group B, both during first-line and salvage CT. When the mobilisation courses were excluded in Group A, the use of G-CSF was more common during salvage treatment than during primary treatment (27 out of 81 vs. 16 out of 85, p < 0.05). Also, in Group B the use of G-CSF was more common during salvage CT than during primary treatment (10 out of 85 vs. 0 out of 73, p < 0.01). Grade 3-4 thrombocytopenia was seen in nine out of 81 courses (11.1%) in Group A but in none of the 85 courses (0%) in Group B (p<0.05). No platelet transfusion was needed during salvage treatment. The mean interval of courses in salvage CT was 27.7 days (range 19-71) in Group A and 27.5 days (range 18-120) in Group B (p = ns). Overall survival was 40.4 months in Group A and 33.0 months in Group B (p < 0.1). CONCLUSION: Salvage treatment after HDC was well-tolerated when given with G-CSF support. Salvage chemotherapy could be carried out with the same doses and intervals both for patients treated earlier with HDC and conventional CT.
UI - 12209723
AU - Bristow RE; Gossett DR; Shook DR; Zahurak ML; Tomacruz RS; Armstrong DK;
TI - Montz FJ Recurrent micropapillary serous ovarian carcinoma.
SO - Cancer 2002 Aug 15;95(4):791-800
AD - The Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-1246, USA. email@example.com
BACKGROUND: The objectives of the current study were to: 1) characterize the clinical outcome of patients with recurrent micropapillary serous ovarian carcinoma (MPSC) and 2) evaluate the survival impact of secondary cytoreductive surgery and other prognostic variables. METHODS: Twenty-six patients with recurrent MPSC were identified retrospectively from hospital and tumor registry databases. Survival curves were generated from the time of tumor recurrence using the Kaplan-Meier method and statistical comparisons were performed using the log-rank test, logistic regression analysis, and the Cox proportional hazards regression model. RESULTS: The median age of the patients at the time of recurrence was 46 years. The mean progression-free interval was 31.6 months, and 92% of patients had advanced stage disease at the time of the initial diagnosis. Twenty-one patients underwent secondary cytoreductive surgery; tumor debulking was performed in 90.5% of cases and 52.4% of patients required an intestinal resection. Optimal resection (residual disease < or = 1 cm) was achieved in 15 patients (71.4%). Patients undergoing optimal secondary cytoreduction had a median survival time of 61.2 months from the date of disease recurrence, compared with 25.5 months for those patients in whom suboptimal residual disease remained (P < 0.02) and 29.9 months for nonsurgical patients (P < 0.01). On multivariate analysis, optimal secondary cytoreduction was found to be the only independent predictor of survival. Salvage chemotherapy produced an objective response in 25% of patients with measurable disease. The administration of chemotherapy prior to surgical intervention was associated with a trend toward worse survival and a lower likelihood of optimal secondary cytoreduction. CONCLUSIONS: Optimal secondary cytoreductive surgery is feasible in the majority of patients with recurrent MPSC and is an independent predictor of subsequent survival. Surgical intervention should be considered for those patients with recurrent MPSC. [See editorials on pages 675-6 and 677-80, this issue.] Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10789
UI - 11994764
AU - Patyanik M; Mayer A; Polgar I
TI - Results of ovary tumor treatment with abdominally administered (198)Au evaluated on the basis of long term follow up.
SO - Pathol Oncol Res 2002;8(1):54-7
AD - Uzsoki Hospital Uzsoki utca 29, Budapest, 1145, Hungary.
In the period between 1959 and 1980 165 patients previously operated with ovarian tumor were treated by intraperitoneally administered (198)Au in the Oncoradiological Centre of the Uzsoki Hospital. The stage distribution of the 158 patients with common epithelial histology was as it follows: Stage I/A 31; Stage I/B 9; Stage I/C 59; Stage II/A 19; Stage II/B 11; Stage II/C 7, Stage III/A 22. The five year survival result is the next: Stage I/A 90%; Stage I/B 78%; Stage I/C 58%; Stage II/A 26%; Stage II/B 27%; Stage II/C 14%; Stage III/A 18%. From the other 7 patients six had sex cord tumor and one lipid cell tumor. The number of the side effects is in good agreement with the data in literature. The use of (198)Au for intraperitoneal treatment of ovary tumors is not contemporary today because of gamma radiation of radiogold, but intraperitoneal radiation treatment should not be forgotten.
UI - 12109222
AU - Schmidbauer S; Sitzmann G; Trupka A; Hallfeldt KK
TI - [Laparoscopic colostomy: experience in patients with ovarian or ano-rectal cancer, non-operable or with rectovaginal fistula]
SO - G Chir 2002 Mar;23(3):101-3
AD - Chirurgische Klinik und Poliklinik, Klinikum Innestadt Ludwig-Maximilians Universitaet Muenchen. carried out in 23 patients with advanced ovarian cancer, inoperable carcinoma of the anorectum or rectovaginal fistulas. There were no intraoperative or postoperative complications and postoperative recovery was rapid with all patients having function of the colostomy within 24 hrs and regaining their preoperative state of mobility on the second postoperative day. The laparoscopic approach allows the careful selection of the colostomy site, easy mobilisation of the colon, causing only little disruption to the intestinal function hence improving postoperative recovery. From Authors' experience, laparoscopic colostomy is a simple and safe operation in most cases and can be used as the preferred technique of intestinal diversion.
UI - 12132060
AU - Gottschalk A; Freitag M; Burmeister MA; Becker C; Horn EP; Standl T
TI - Patient-controlled thoracic epidural infusion with ropivacaine 0.375% provides comparable pain relief as bupivacaine 0.125% plus sufentanil after major abdominal gynecologic tumor surgery.
SO - Reg Anesth Pain Med 2002 Jul-Aug;27(4):367-73
AD - Department of Anesthesiology, University Hospital Eppendorf, Hamburg, Germany. firstname.lastname@example.org
BACKGROUND AND OBJECTIVES: We tested the hypothesis that an opioid-free local anesthetic alone is able to provide comparable analgesia to the opioid supplemented epidural application of local anesthetics using thoracic epidural catheters after major abdominal surgery. METHODS: In a prospective, randomized, and double-blind study, we have compared the analgesic efficacy and side effects of ropivacaine 0.375% (group R) versus bupivacaine 0.125% in combination with sufentanil 0.5 microg/mL(-1) (group B/S) via a thoracic epidural catheter for a duration of 96 hours after major abdominal surgery in 30 gynecologic tumor patients. Piritramide was given for breakthrough pain. Assessments were performed every 12 hours after start of the epidural infusion using continuous (first 24 hours) and patient-controlled epidural analgesia (PCEA) (24 to 96 hours). RESULTS: No differences were seen in demographic and perioperative data. Dynamic pain scores (visual analog scale [VAS] values) were comparable between groups during mobilization (group R v group B/S: 24 hours: 40 +/- 30 v 36 +/- 14, P =.9; 48 hours: 46 +/- 33 v 42 +/- 25, P =.93; 72 hours: 42 +/- 24 v 48 +/- 26, P =.78; 96 hours: 42 +/- 25 v 29 +/- 28, P =.49) and on coughing during the whole study period. Hemodynamics, intensity of motor block (Bromage scale), and side effects like nausea, vomiting, pruritus, and bladder disfunction also did not differ between groups. CONCLUSION: The present study shows that thoracic epidural infusion of ropivacaine 0.375% provides comparable pain relief and incidence of side effects after major abdominal gynecologic surgery as bupivacaine 0.125% in combination with 0.5 microg/mL(-1) sufentanil and may therefore represent an alternative in epidural pain management.
UI - 12144679
AU - Griffiths CT; Parker LM; Lee S; Finkler NJ
TI - The effect of residual mass size on response to chemotherapy after surgical cytoreduction for advanced ovarian cancer: long-term results.
SO - Int J Gynecol Cancer 2002 Jul-Aug;12(4):323-31
AD - Dana Farber Cancer Institute, the Brigham & Women's Hospital, Boston, MA, USA.
We report an observational study of chemotherapeutic regression of ovarian tumor implants according to decrements in residual mass size after surgical cytoreduction. Cytoreductive operations were attempted on 74 consecutive patients with stages IIIB-IV disease referred for this purpose. Thirty-two patients had received one to four courses of preoperative chemotherapy (22 responses, no progressions). Postoperative chemotherapy followed current protocols at Dana Farber Cancer Institute (n=61) or referring institutions (n=13); 57 regimens contained cisplatin. Postchemotherapy response was assessed clinically or by second-look procedures. Negative findings were considered a complete remission. Masses > 1 cm were excised from 62 patients. Twelve patients were inoperable. Twenty-eight patients had complete remissions and the correlation between these and decrements in residual mass size was highly significant (P < 0.0001). Complete remissions had a uniform effect and were the only outcome predictive of survival. Preoperative treatment greatly facilitated cytoreduction but only masses 0-0.2 cm were sensitive to postoperative chemotherapy. Masses 0.5 cm or less were optimal. They made up 77% of operable patients and supplied 25 (89%) of the complete remissions. Cytoreduction is not always required but even large-volume disease in the upper abdomen can be safely excised. The concept that masses larger than 10 cm indicate general chemoresistance has not been sustained.
UI - 12144680
AU - Kitchener HC
TI - Clinical practice guidelines: loss of clinical freedom or a coming of age?
SO - Int J Gynecol Cancer 2002 Jul-Aug;12(4):332-6
AD - Academic Unit of Obstetrics and Gynaecology, St. Mary's Hospital, Whitworth Park, Manchester M13 0JH, United Kingdom. email@example.com
When a woman presents to us with gynecological cancer our duty is to offer the most effective means of treatment; that which maximizes the potential for cure at the same maintaining or improving quality of life. For the majority of our patients we are able to contemplate cure but for many, particularly those with advanced ovarian cancer, this will not be possible although we can provide the prospect of several years of survival. In an international context our ability to provide optimal care depends largely on the healthcare resources which are affordable, and although in many parts of the world these are very limited, the same principles apply. This series of articles will put the spotlight on effective care in gynaecological oncology following an evidence based theme. The articles will be informative, punchy and provocative. The first of these contributions looks at clinical guidelines: what are they for, how do we produce them