National Cancer Institute®
Last Modified: November 21, 2001
UI - 21411916
AU - Wu CH; Yang CH; Lee JN; Hsu SC; Tsai EM
TI - Weekly and monthly regimens of paclitaxel and carboplatin in the management of advanced ovarian cancer. A preliminary report on side effects.
SO - Int J Gynecol Cancer 2001 Jul-Aug;11(4):295-9
AD - Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
This preliminary study was carried out over 18 months to evaluate whether the side effects in patients with advanced ovarian cancer receiving chemotherapy using paclitaxel-carboplatin differed between weekly (98 cycles in 14 patients) and monthly (102 cycles in 15 patients) administrations. We used paclitaxel (60 mg/m2) and carboplatin (AUC of 2) in the weekly regimen and 175 mg/m2 of paclitaxel and carboplatin (AUC of 6) in the monthly regimen. All eligible patients received at least four cycles of treatment in both regimens. The results revealed significantly decreased hematological toxicity in weekly regimens relative to monthly ones, ie, 7.1% vs. 18.6% of anemia (> or = grade 2), 7.1% vs. 32.3% of grade 3/4 granulocytopenia, and 0% vs. 15.7% of >grade 2 thrombocytopenia. There was no significant difference in nonhematological toxicities between the two regimens. The incidence of unscheduled events was much less in the weekly regimen than in the monthly one; ie, delayed treatment (3 vs. 18 events), unanticipated hospitalizations (3 vs. 15 times), and supplemental support with G-CSF (7 vs. 33 times). Complete responses were observed in 6 of 14 patients in the weekly regimen and in five of 15 patients in the monthly regimen, while partial responses were seen in four and five patients in the weekly and monthly regimens, respectively. The present results demonstrate that the weekly regimen can achieve the benefits of tolerable toxicity with significantly reduced myelosuppression and improved cost-effectiveness in terms of unscheduled events.
UI - 21411917
AU - Bafna UD; Umadevi K; Kumaran C; Nagarathna DS; Shashikala P; Tanseem R
TI - Germ cell tumors of the ovary: is there a role for aggressive cytoreductive surgery for nondysgerminomatous tumors?
SO - Int J Gynecol Cancer 2001 Jul-Aug;11(4):300-4
AD - Department of Gynaecologic Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India. firstname.lastname@example.org
Thirty-three patients with germ cell tumor of the ovary were seen at Kidwai Memorial Institute of Oncology (KMIO), Bangalore, between 1996 and 1999. Twelve patients had endodermal sinus tumor (EST), 11 dysgerminoma, seven mixed germ cell tumor, and three immature teratoma. Thirteen patients had bulky residual disease of >10 cm after the primary surgery. All but one patient received a combination of bleomycin, etoposide, and cisplatin (BEP) either as neoadjuvant (NACT, 3 cases) or as adjuvant therapy (28 cases). In the present study, all 11 patients with dysgerminoma achieved sustained complete remission (CR), irrespective of the size of residual disease at the time of chemotherapy. Four out of six cases (66.6%) with bulky nondysgerminomatous tumor achieved CR, which was sustained in three cases and one recurred. Fifteen of the remaining 16 (93.7%) nonbulky, nondysgerminomatous tumors achieved CR, which was sustained in 14 cases and recurred in one. This study indicates that there may be a role for aggressive cytoreductive surgery, either primary/interval or at the time of second-look laparotomy, in selected patients with nondysgerminomatous germ cell tumor of the ovary.
UI - 21455242
AU - Penson RT; Supko JG; Seiden MV; Fuller AF; Berkowitz RS; Goodman A;
TI - Campos SM; MacNeill KM; Cook S; Matulonis UA A Phase I-II study of 96-hour infusional topotecan and paclitaxel for patients with recurrent Mullerian tumors.
SO - Cancer 2001 Sep 1;92(5):1156-67
AD - Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114-2617, USA.
BACKGROUND: Topotecan and paclitaxel are schedule dependent chemotherapeutic agents with activity against ovarian carcinoma. A Phase I-II study in which both drugs were administered concurrently by 96-hour, continuous, intravenous infusion was performed to determine the maximum tolerated dose (MTD), toxicities, pharmacokinetics, and efficacy of the combination. METHODS: Women with ovarian or primary peritoneal carcinoma and documented recurrent disease were eligible for the study. The dose of topotecan was escalated from 1.6 mg/m(2) while maintaining the paclitaxel dose constant at 100 mg/m(2). Plasma concentrations of both drugs were monitored daily during the first cycle of therapy. RESULTS: Forty-five patients with a median age of 54 years (range, 42-70 years) received 181 cycles of therapy. Five patients were recruited to each of four dose levels (topotecan 1.6 mg/m(2), 2.0 mg/m(2), 2.8 mg/m(2), and 3.6 mg/m(2)), and an additional 25 patients were treated at the MTD (Phase II). Neutropenia and thrombocytopenia became dose limiting toxicities (DLT) at the fourth dose level. Emesis, mucositis, peripheral neuropathy, diarrhea, and alopecia were mild. Twenty patients (44%) had line-related occlusion, thrombosis, or infection. The mean values (+/- standard deviation) of the apparent steady-state plasma concentrations at the Phase II doses were 2.3 nM +/- 0.5 nM for topotecan lactone, 5.6 nM +/- 2.1 nM for total topotecan, and 40.1 nM +/- 16.8 nM for paclitaxel. There were seven partial responses (Phase II) contributing to an objective response rate of 28% and a median survival time of 11.7 months (range, 0.6-20.1 months). CONCLUSIONS: Topotecan at a dose of 2.8 mg/m(2) and paclitaxel at a dose of 100 mg/m(2) administered by concurrent, 96-hour, continuous intravenous infusions shows activity against tumors of Mullerian origin. Copyright 2001 American Cancer Society.
UI - 21259463
AU - Laport GG; Fleming GF; Waggoner S; Zimmerman TM; Grinblatt DL; Williams
TI - SF A phase II trial of docetaxel for peripheral blood stem cell mobilization for patients with breast cancer and ovarian cancer.
SO - Bone Marrow Transplant 2001 Apr;27(7):677-81
AD - The University of Chicago, Division of Hematology/Oncology, Chicago, IL, USA.
As docetaxel is known to have significant antineoplastic activity against breast and ovarian cancer, we explored its application as a peripheral blood stem cell mobilizing agent in 33 women with stage lll-IV ovarian carcinoma (n = 10) or stage ll-lV breast cancer (n = 23) who were in preparation for high-dose chemotherapy. Eleven patients had bone and/or bone marrow involvement with their disease. The median number of prior regimens received before mobilization was two (range 1-3). The three dose levels administered were 100 mg/m(2), 110 mg/m(2) and 120 mg/m(2). Patients received one dose of docetaxel in the outpatient setting followed by G-CSF (10 microg/kg/day) starting 4 days after docetaxel administration. Leukapheresis commenced when WBC >1.0 x 10(9)/l or when the WBC began to rise after reaching a nadir. Ninety-seven percent of patients began leukapheresis within 7-9 days after receiving docetaxel (range 7-10 days). The collection goal was >/=2 x 10(6) CD34(+) cells/kg. Twenty-seven (82%) patients reached this goal in a median of 2 leukapheresis days (range 1-3). No grade 2-4 nonhematologic toxicities were noted. Thirteen patients (55%) showed a WBC nadir >1.0 x 10(9)/l. None of the patients experienced neutropenic fever or required blood or platelet transfusion support. In conclusion, docetaxel + G-CSF is an effective, well-tolerated regimen for PBPC mobilization which can be safely administered in the outpatient setting with minimal toxicity.
UI - 21426824
AU - Favalli G; Odicino F; Pecorelli S
TI - Surgery of advanced malignant epithelial tumours of the ovary.
SO - Forum (Genova) 2000 Oct-Dec;10(4):312-20
AD - Dipartimento di Oncologia Ginecologica, Spedali Civili, Universita degli Studi di Brescia, Italy.
Surgery is still the cornerstone in the management of advanced epithelial ovarian cancer (AEOC) patients. It involves: i. establishment of diagnosis and staging; ii. primary cytoreduction; iii. interval cytoreduction, interval debulking surgery (IDS) or surgery after neoadjuvant chemotherapy; iv. secondary cytoreduction during the assessment of the status of the disease at the end of primary chemotherapy - second look; v. surgery for recurrence; vi. palliation. Substantial evidence exists to demonstrate that if surgery is performed by gynaecologists with a special training in gynaecological oncology, a survival advantage can be achieved when compared with that obtained when general surgeons are primarily treating AEOC. Primary surgery with diagnostic and cytoreductive intent should be performed in accordance with the European Guidelines of Staging in Ovarian Cancer. Whether or not cytoreduction should systematically include lymphadenectomy is still a controversial issue. The strong correlation between chemosensitivity, successful debulking surgery and survival strongly support the concept that it is the biological characteristic of the disease rather than the aggressiveness of the surgeon to allow a successful cytoreduction to the real optimal disease status. It should be now recognised as the complete absence of disease at the end of the surgical procedure. Both IDS and neoadjuvant chemotherapy represent a strong effort to achieve such a status through less morbidity and a better quality of life for the patient. Surgery for recurrence and palliation need to be optimised both in terms of patient selection and a better integration with chemotherapy and ancillary management.
UI - 21426825
AU - Colombo N; Parma G; Bocciolone L; Franchi D; Sideri M; Maggioni A
TI - Medical therapy of advanced malignant epithelial tumours of the ovary.
SO - Forum (Genova) 2000 Oct-Dec;10(4):323-32
AD - Istituto Europeo di Oncologia, Divisione di Ginecologia Oncologica, Milano, Italy.
Despite improvements seen in median and overall survival using a combination of platinum-compounds and paclitaxel (PTX), long-term survival rates for patients with advanced epithelial ovarian carcinoma remain disappointing and ongoing efforts have aimed to develop more effective primary therapy. In the early 1990Os the drug PTX was first tested in ovarian cancer. In the Gynaecological Oncology Group (GOG) trial 111 the cisplatin (CP)+PTX regimen was judged to be superior compared to the platinum-based control arm with an improvement of overall response rate, median progression-free interval and overall median survival. These favourable data were confirmed by a European-Canadian Intergroup trial (OV10). In contrast, in a further GOG trial (GOG132) there was no difference in survival between CP alone and the combination of PTX and CP. The International Collaborative Ovarian Neoplasm Study (ICON)3 is the first and only trial comparing PTX plus carboplatin against carboplatin alone or a (non-taxane) CP-based control arm. The last analysis performed with a total of 1,293 events showed an estimated absolute difference in one-year progression-free survival of 1% and in two-year overall survival of 2% both in favour of PTX plus carboplatin. The results of ICON3, in accordance with GOG132 study, appear to contradict the earlier positive results seen for PTX and CP in the GOG-111 and OV10 trials and suggested that single agent carboplatin, CY-adriamycin-CP are safe and effective first-line treatments for women requiring chemotherapy for ovarian cancer. A meta-analysis with individual patient data is warranted to better clarify the issue of PTX in the front line therapy of advanced ovarian cancer. Salvage chemotherapy is often utilised in patients with advanced ovarian cancer, due to the high frequency of recurrent disease even after a clinical or pathological complete response after primary chemotherapy. Main objectives of salvage chemotherapy include: i. improvement in quality of life and symptoms; ii. tumour load reduction and survival advantage; iii. evaluation of potentially active new drugs to be included in first-line. Since the goal is palliation in most cases, monotherapy is generally indicated. However, the chances of response are directly related to the treatment-free interval, with a response rate nearly equivalent to that of primary chemotherapy when the treatment-free interval exceeds 24 months. Extension of the platinum-free interval before re-treatment with platinum or taxanes may allow partial reversal of resistance to these agents which can therefore still show significant activity in relapsing patients. Unfortunately, durable response to salvage chemotherapy is rare and cure is almost impossible. The sequential use of the agents currently available for salvage treatment in monotherapy may transform ovarian cancer into a chronic disease and confers long survival to the patients. Perhaps, the most interesting role of second-line chemotherapy is to identify new potentially active drugs, which can be moved up-front. Most of the compounds used in second line (gemcitabine, topotecan, liposomal doxorubicin) are in fact under investigation to develop alternative schedules and sequences of drug administration. A new phase III multi-national randomised study for patients with advanced stage epithelial ovarian or primary periperitoneal carcinoma will evaluate the impact of incorporating a new drug within either a platinum-based triplet (new drug + platinum + PTX) or a sequential-doublet (new drug + platinum followed by platinum + PTX) in order to identify one or more experimental regimens able to improve long-term survival with acceptable toxicity.
UI - 21426826
AU - Cardenes H; Randall ME
TI - Radiotherapy in epithelial ovarian cancer: state of the art.
SO - Forum (Genova) 2000 Oct-Dec;10(4):335-52
AD - Department of Radiation Oncology, Indiana University School of Medicine, Indiana 46202, USA.
Modern advances in surgery, chemotherapy (CT) and radiotherapy (RT) have not, unfortunately, impacted the overall survival for patients with ovarian cancer (OC). Despite its long history in the treatment of OC and its proven curative role in patients with microscopic or minimal residual disease, the proper role of RT in the management of OC is controversial and not clearly established. Similarly, the potential roles of RT in the consolidative treatment and as salvage therapy following CT failure remain controversial. In the present review current issues in the radiotherapeutic management are discussed along with possible future clinical research directions.
UI - 21426827
AU - Schwartz PE
TI - Surgery of germ cell tumours of the ovary.
SO - Forum (Genova) 2000 Oct-Dec;10(4):355-65
AD - Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
The surgical management of germ cell tumours of the ovary is based on the premise of preserving fertility. Ovarian germ cell tumours occur in young women in whom fertility preservation is of great concern. Overwhelmingly ovarian germ cell tumours are benign, the most common form of which is the benign cystic teratoma (dermoid cyst). Cystectomies with preservation of the ovarian remnant should be the routine surgical treatment of benign cystic teratomas. Management of ovarian germ cell malignancies also focuses on preservation of fertility. These tumours, with the exception of dysgerminoma are overwhelmingly unilateral. All are exquisitely sensitive to cytotoxic chemotherapy and fertility has been preserved and successful conception has occurred even in women with advanced stage disease following surgery and chemotherapy. Cytoreductive surgery plays a role in the treatment of non-dysgerminomatous ovarian germ cell malignancies, but is not necessary for the management of ovarian dysgerminomas as the latter are exquisitely sensitive to chemotherapy. Second-look surgery is no longer routinely recommended in the management of these disorders due to the low incidence of positivity when patients have been treated with modern combination chemotherapy. The role of surgery in the management of recurrent disease has yet to be established due to the low incidence of persistent disease following modern combination chemotherapy.
UI - 21426828
AU - Newlands ES
TI - Management of ovarian germ cell tumours.
SO - Forum (Genova) 2000 Oct-Dec;10(4):368-80
AD - Medical Oncology Department, Charing Cross Hospital, London, England.
Malignant ovarian germ cell tumours are rare but they occur in women with a mean age of 19 years. It is important that these young patients are not subjected to radical surgery. In most of these patients, they can be cured with either surgery alone and careful surveillance with a combination of clinical examination, computer tomography scanning and serial serum tumour markers. Almost all of those with metastatic disease can be cured with cisplatin-based chemotherapy. A relapse is rare and most of these young patients will recover menstruation within two to six months of completing their chemotherapy and provided they have not had radical surgery, most of these patients should be able to complete their families normally.
UI - 21464099
AU - Fuse K; Tanaka T; Kagaya H; Suzuki T; Kimura A
TI - [Adverse effect of paclitaxel plus carboplatin combination therapy related to administration schedule in patients with ovarian cancer]
SO - Gan To Kagaku Ryoho 2001 Sep;28(9):1295-7
AD - Dept. of Pharmacy, Saiseikai Yokohama-shi Nambu Hospital.
UI - 21463153
AU - Clarke-Pearson DL; Van Le L; Iveson T; Whitney CW; Hanjani P; Kristensen
TI - G; Malfetano JH; Beckman RA; Ross GA; Lane SR; DeWitte MH; Fields SZ Oral topotecan as single-agent second-line chemotherapy in patients with advanced ovarian cancer.
SO - J Clin Oncol 2001 Oct 1;19(19):3967-75
AD - Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710-0001, USA. email@example.com
PURPOSE: To evaluate oral topotecan as single-agent, second-line therapy in patients with ovarian cancer previously treated with a platinum-based regimen. PATIENTS AND METHODS: Patients (N = 116) received oral topotecan 2.3 mg/m2 daily for 5 days every 21 days. Eligibility criteria included histologic diagnosis of International Federation of Gynecology and Obstetrics stage III or IV epithelial ovarian cancer, bidimensionally measurable disease, prior platinum-containing chemotherapy, age > or = 18 years, performance status < or = 2, and life expectancy > or = 12 weeks. RESULTS: Overall response rate was 21.6% (25 of 116 patients). Median duration of response was 25.0 weeks; median time to response was 8.4 weeks. Median time to progression was 14.1 weeks; median survival was 62.2 weeks. Grade 4 neutropenia was experienced by 50.4% of patients in 13.4% of courses administered. Grade 4 thrombocytopenia was experienced by 22.1% of patients in 5.1% of courses. Grade 3 or 4 anemia was experienced by 29.2% of patients in 8.5% of courses. Most frequent nonhematologic toxicities were predominantly (> 90%) grade 1 or 2 and included nausea, alopecia, diarrhea, and vomiting. CONCLUSION: Second-line oral topotecan administered at 2.3 mg/m2 for 5 days every 21 days demonstrated activity in patients with progressive or recurrent ovarian cancer after first-line platinum-based chemotherapy. This activity was comparable to that seen in previous studies with intravenous topotecan. Grade 4 neutropenia was less frequent with oral topotecan than previously reported for intravenous topotecan. Oral topotecan is an active, tolerable, and convenient formulation of an established agent for the second-line treatment of advanced epithelial ovarian cancer and may also facilitate exploring prolonged treatment schedules.
UI - 21415890
AU - Seiden MV
TI - Ovarian cancer.
SO - Oncologist 2001;6(4):327-32
AD - Division of Hematology and Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. Mseiden@partners.org
Ovarian cancer remains the most lethal gynecologic malignancy in women in the United States. Studies from this year's American Society of Clinical Oncology more clearly defined the role of chemotherapy in women with early stage disease and now suggest that essentially all women with invasive disease should receive chemotherapy that contains carboplatin. Studies in women with advanced disease continue to support the use of carboplatin and paclitaxel in the treatment of women with newly diagnosed disease although early data suggest that carboplatin and docetaxel might be an acceptable alternative. Platinum-resistant disease remains a therapeutic challenge. Small molecules that inhibit the function of the epidermal growth factor receptor, such as OSI-774, and novel classes of chemotherapeutic agents, including the acylfulvene MGI-114 and epothilone B and its analogue, BMS247550, all warrant further study in this disease.
UI - 21469631
AU - Schenk PW; Boersma AW; Brandsma JA; den Dulk H; Burger H; Stoter G;
TI - Brouwer J; Nooter K SKY1 is involved in cisplatin-induced cell kill in Saccharomyces cerevisiae, and inactivation of its human homologue, SRPK1, induces cisplatin resistance in a human ovarian carcinoma cell line.
SO - Cancer Res 2001 Oct 1;61(19):6982-6
AD - Department of Medical Oncology, University Hospital Rotterdam-Daniel den Hoed Cancer Center, Josephine Nefkens Institute, 3000 DR Rotterdam, the Netherlands.
The therapeutic potential of cisplatin, one of the most active and widely used anticancer drugs, is severely limited by the occurrence of cellular resistance. In this study, using budding yeast Saccharomyces cerevisiae as a model organism to identify novel drug resistance genes, we found that disruption of the yeast gene SKY1 (serine/arginine-rich protein-specific kinase from budding yeast) by either transposon insertion or one-step gene replacement conferred cellular resistance to cisplatin. Heterologous expression of the human SKY1 homologue SRPK1 (serine/arginine-rich protein-specific kinase) in SKY1 deletion mutant yeast cells restored cisplatin sensitivity, suggesting that SRPK1 is a cisplatin sensitivity gene, the inactivation of which could lead to cisplatin resistance. Subsequently, we investigated the role of SRPK1 in cisplatin sensitivity and resistance in human ovarian carcinoma A2780 cells using antisense oligodeoxynucleotides. Treatment of A2780 cells with antisense oligodeoxynucleotides directed against the translation initiation site of SRPK1 led to down-regulation of SRPK1 protein and conferred a 4-fold resistance to cisplatin. The human SRPK1 gene has not been associated with drug resistance before. Our new findings strongly suggest that SRPK1 is involved in cisplatin-induced cell kill and indicate that SRPK1 might potentially be of importance for studying clinical drug resistance.
UI - 21290398
AU - Treat J; Damjanov N; Huang C; Zrada S; Rahman A
TI - Liposomal-encapsulated chemotherapy: preliminary results of a phase I study of a novel liposomal paclitaxel.
SO - Oncology (Huntingt) 2001 May;15(5 Suppl 7):44-8
AD - Department of Medical Oncology, Fox Chase-Temple Cancer Center, Philadelphia, Pennsylvania, USA. firstname.lastname@example.org
Liposome encapsulation of antineoplastic drugs entered clinical testing in the late 1980s. As carriers for a variety of agents, liposomes can allow successful delivery of agents that may be subject to rapid degradation in the serum and can modify the toxicity profile. In general, liposomes have demonstrated an ability to attenuate toxicities by their different pharmacokinetic profile and pattern of distribution. Differences in the constitution of the liposome can greatly affect the pharmacokinetic profile resulting in different patterns of toxicity. Characteristics such as size, charge, composition, and integrity can affect performance of the liposome. Liposome encapsulation of doxorubicin has been shown to reduce cardiac toxicity. Preliminary data suggest that encapsulation of paclitaxel can greatly modify neurotoxicity without the need for cremephor.
UI - 21476344
AU - Nardi M; De Marco S; Fabi A; Aloe A; Magnani E; Pacetti U; Carlini P;
TI - Ruggeri EM; Cognetti F Cisplatin and escalating doses of paclitaxel and epirubicin in advanced ovarian cancer. A phase I study.
SO - Cancer Chemother Pharmacol 2001 Sep;48(3):255-8
AD - Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy. email@example.com
PURPOSE: The combination of paclitaxel and cisplatin is considered the standard regimen for advanced ovarian cancer (AOC). A meta-analysis has shown that the incorporation of anthracyclines into first-line chemotherapy might improve long-term survival by 7-10%. We designed a phase I-II study in patients with AOC using a combination of a fixed dose of cisplatin with paclitaxel and epirubicin both given at escalating doses every 3 weeks. The objectives of this study were to determine both the maximum tolerated dose (MTD) and the antitumor activity of this combination. METHODS: Six different dose levels were planned. The starting doses were cisplatin 75 mg/m2, paclitaxel 140 mg/m2, and epirubicin 50 mg/m2. The doses of paclitaxel were escalated in 20-mg/m2 increments, alternating with 20-mg/m2 increments of epirubicin. Ten patients with AOC entered the phase I study. Three patients each were enrolled at level I and level II and four patients at level III, and at each level, 15 courses were administered. Patients received a median of five courses. RESULTS: Nonhematological toxicity was generally mild, except for grade 3 mucositis in one course at levels II and III, and grade 3 vomiting in one course at levels I and III. Hematological toxicities were grade 3-4 neutropenia in 60%, 47% and 60% of courses at levels I, II and III, respectively, and grade 3 anemia in one course at level III. At level III two of four patients developed a dose-limiting toxicity which was grade 4 neutropenia lasting more than 1 week. CONCLUSIONS: The MTD was reached at level II with cisplatin 75 mg/m2, paclitaxel 160 mg/m2, and epirubicin 50 mg/m2. The phase II part of the study is currently ongoing.
UI - 21469897
AU - Obermair A; Hagenauer S; Tamandl D; Clayton RD; Nicklin JL; Perrin LC;
TI - Ward BG; Crandon AJ Safety and efficacy of low anterior en bloc resection as part of cytoreductive surgery for patients with ovarian cancer.
SO - Gynecol Oncol 2001 Oct;83(1):115-20
AD - Queensland Centre for Gynaecological Cancer, Royal Women's Hospital, Brisbane, Australia. firstname.lastname@example.org
OBJECTIVE: To examine the feasibility and safety of a low anterior resection of the rectosigmoid plus adjacent pelvic tumour as part of primary cytoreduction for ovarian cancer. METHODS: This study included 65 consecutive patients with primary ovarian cancer who had debulking surgery from 1996 through 2000. All patients underwent an en bloc resection of ovarian cancer and a rectosigmoid resection followed by an end-to-end anastomosis. Parameters for safety and efficacy were considered as primary statistical endpoints for the aim of this analysis. RESULTS: Postoperative residual tumour was nil, <1 cm, and >1 cm in 14, 34, and 14 patients, respectively. The median postoperative hospital stay was 11 days (range, 6 to 50 days). Intraoperative complications included an injury to the urinary bladder in one patient. Postoperative complications included wound complications (n = 14, 21.5%), septicemia (n = 9, 13.8%), cardiac complications (n = 7, 10.8%), thromboembolic complications (n = 5, 7.7%), ileus (n = 2, 3.1%), anastomotic leak (n = 2, 3.1%), and fistula (n = 1, 1.5%). Reasons for a reoperation during the same admission included repair of an anastomotic leak (n = 1), postoperative hemorrhage (n = 1), and wound debridement (n = 1). Wound complications, septicemia, and anastomotic leak formation were more frequent in patients who had a serum albumin level of < or =30 g/L preoperatively. There was one surgically related mortality in a patient who died from a cerebral vascular accident 2 days postoperatively. CONCLUSIONS: An en bloc resection as part of primary cytoreductive surgery for ovarian cancer is effective and its morbidity is acceptably low. Copyright 2001 Academic Press.
UI - 21469899
AU - Gronlund B; Hogdall C; Hansen HH; Engelholm SA
TI - Results of reinduction therapy with paclitaxel and carboplatin in recurrent epithelial ovarian cancer.
SO - Gynecol Oncol 2001 Oct;83(1):128-34
AD - Department of Oncology, Finsen Center, Righospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark. email@example.com
OBJECTIVE: The purpose of the study was to evaluate the treatment results and toxicity of a retreatment regimen of paclitaxel and carboplatin in patients with ovarian cancer relapse. METHODS: A retrospective analysis of 241 consecutive patients with primary epithelial ovarian cancer receiving paclitaxel and a platinum analogue as first-line treatment was performed. Relapse treatment of platinum-sensitive patients consisted of paclitaxel (175 mg/m(2)) over 3 h followed by carboplatin at an area under the concentration-time curve of 5, repeated every 3 weeks. RESULTS: Forty-three patients with relapse were treated with paclitaxel and carboplatin after a median progression-free interval from the end of first-line chemotherapy of 15.8 months (range 6.0-41.7 months). In patients with evaluable disease the overall response rate was 84% (95% CI: 68.0-93.8%). The progression-free survival and overall survival from start of relapse treatment were a median of 9.7 months (range 1.4-26.9 months) and 13.1 months (range 4.5-35.5 months), respectively. In a multivariate Cox analysis independent prognostic factors for progression-free survival after first relapse were response to relapse treatment (P = 0.002, hazard ratio = 13.9) and time to first recurrence (P = 0.016, hazard ratio = 0.167). The planned treatment was accomplished by 67% of patients. Grade 4 neutrocytopenia over 1 week was observed in 9.3% of patients. Grade 1-2 peripheral neuropathy was reported in 30% of patients. Only 1 patient had her paclitaxel dose attenuated because of grade 4 neuropathy. CONCLUSION: Retreatment with paclitaxel and carboplatin in patients with platinum-sensitive epithelial ovarian cancer relapse yielded a high response rate and encouraging progression-free survival and overall survival. Paclitaxel-carboplatin reinduction therapy is generally well tolerated and the toxicity is manageable. Copyright 2001 Academic Press.
UI - 21469887
AU - Bristow RE; Montz FJ
TI - Complete surgical cytoreduction of advanced ovarian carcinoma using the argon beam coagulator.
SO - Gynecol Oncol 2001 Oct;83(1):39-48
AD - The Kelly Gynecologic Oncology Service, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-1248, USA. firstname.lastname@example.org
OBJECTIVE:The aim of this study was to evaluate the utility of the argon beam coagulator (ABC) in achieving optimal (< or =1 cm) disease status and facilitating the conversion of optimal but visible disease (0.1-1.0 cm) to microscopic residual disease (complete cytoreduction) among patients with advanced ovarian carcinoma. METHODS: All patients undergoing their primary attempt at surgical cytoreduction for Stage IIIB-IV epithelial ovarian carcinoma between October 1, 1997 and June 30, 2000 were identified from the tumor registry database. Data were abstracted retrospectively and included: the size/location of precytoreduction disease, surgical procedures performed, the anatomic regions in which the ABC was used for cytoreduction, the size/location of residual tumor, and the date of last follow-up and disease status. Survival curves were generated using the Kaplan-Meier method, and statistical comparisons were performed using the chi(2) test, Fisher's exact test, log rank test, and multivariate logistic regression. RESULTS: Forty-five patients were identified (FIGO Stage IIIB = 8, Stage IIIC = 29, Stage IV = 8). Overall, optimal cytoreduction was achieved in 84.4% of patients; 60.0% had only microscopic residual and 24.4% had residual disease 0.1-1.0 cm. The ABC was used to facilitate cytoreduction in 31 patients. Optimal disease status was achieved in 93.6% of cases in which the ABC was used compared with 64.3% for non-ABC cases (P < 0.023). ABC use was also associated with a higher rate of complete cytoreduction (74.2%) compared with non-ABC cases (28.6%, P < 0.004). Among patients left with optimal disease (< or =1 cm), conversion to only microscopic residual was achieved in 79.3% of cases using the ABC and 44.4% of cases without ABC use (P < 0.044). The ABC was associated with a statistically significantly higher rate of complete cytoreduction for disease located in the lesser sac/gastrocolic ligament (90.9% vs 14.3%), abdominal peritoneum (95.5% vs 50.0%), bowel mesentery (80.0% vs 0), and pelvis (89.3% vs 50.0%). Multivariate analysis revealed that use of the ABC (P = 0.006) and disease in three or fewer anatomic regions (P = 0.014) were independent predictors of a microscopic residual surgical outcome. Complete cytoreduction was associated with a significant advantage in median progression-free survival (22.2 months) compared with patients with optimal but visible (0.1-1.0 cm) residual disease (12.3 months) and those with suboptimal (>1.0 cm) residual disease (6.3 months, P < 0.001). Among ABC cases, the mean estimated blood loss was 527 ml, and major postoperative complications occurred in 9.7% of patients. CONCLUSIONS: The ABC is a useful adjunct to conventional tumor reductive techniques and appears to significantly increase the feasibility of achieving both optimal disease status and complete cytoreduction of all visible tumor in patients with macroscopic metastatic ovarian carcinoma. Copyright 2001 Academic Press.
UI - 21469888
AU - Bristow RE; Smith Sehdev AE; Kaufman HS; Montz FJ
TI - Ablation of metastatic ovarian carcinoma with the argon beam coagulator: pathologic analysis of tumor destruction.
SO - Gynecol Oncol 2001 Oct;83(1):49-55
AD - The Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. email@example.com
OBJECTIVE: The aim of this study was to characterize the histopathologic effects of electrosurgical tumor destruction of metastatic ovarian carcinoma using the argon beam coagulator (ABC) and evaluate the depth of tissue damage produced by a range of power settings and tissue interaction times. METHODS: Epithelial ovarian carcinoma tumor specimens (1 cm(3)) were harvested intraoperatively. Following surgical excision, electrosurgical destruction of tumor was effected using the ABC at three power settings (60, 80, and 100 W) and three tissue interaction time intervals (1, 3, and 5 s), yielding nine experimental groups of 16 samples each (n = 144). Samples were formalin-fixed, cross-sectioned, stained with hematoxylin and eosin, and examined microscopically for histologic characteristics and depth of tissue destruction. RESULTS: Microscopic evaluation revealed that the total depth of destruction (TDD) produced by the ABC was composed of three distinct zones of tissue injury: vaporization, carbonized eschar (ESC), and coagulative necrosis (NEC). For each power setting, the mean TDD increased in a linear fashion as the interaction time interval increased from 1 to 5 s (60 W, 1.71 to 2.43 mm; 80 W, 2.24 to 3.69 mm; 100 W, 3.21 to 5.58 mm). By regression analysis, both power setting and tissue interaction time were independently associated with increasing TDD, with power having the strongest effect. At all power settings and interaction time intervals, the incremental change in TDD was primarily a function of the degree of tissue vaporization, which increased from 0.59 mm at 60 W (1 s) to 3.22 mm at 100 W (5 s). For all experimental groups, the ratio of NEC/ESC was highly consistent, ranging from 1.03 to 1.33 (P > 0.05, Bonferroni multiple comparisons procedure), and demonstrated that for each resulting ESC, an equivalent or greater degree of underlying NEC was also present. CONCLUSIONS: The destruction of ovarian carcinoma tumor tissue produced by the ABC is dependent upon both power setting and tissue interaction time. Increasing depth of destruction is due predominantly to a deeper level of tissue vaporization. The NEC/ESC ratio provides a reliable means of estimating the true depth of tumor destruction produced by the ABC and may contribute to increased safety and efficacy of electrosurgical cytoreduction of using this technique. Copyright 2001 Academic Press.
UI - 21477744
AU - Pejovic T; Nezhat F
TI - Laparoscopic management of adnexal masses the opportunities and the risks.
SO - Ann N Y Acad Sci 2001 Sep;943():255-68
AD - Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Suspected ovarian neoplasm is a common clinical problem affecting women of all ages. Although the majority of adnexal masses are benign, the primary goal of diagnostic evaluation is the exclusion of malignancy. It has been estimated that approximately 5-10% of women in the United States will undergo a surgical procedure for a suspected ovarian neoplasm during their lifetime. Despite the magnitude of the problem, there is still considerable disagreement regarding the optimal surgical management of these lesions. Traditional management has relied on laparotomy to avoid undertreatment of a potentially malignant process. Advances in detection, diagnosis, and minimally invasive surgical techniques make it necessary now to review this practice in an effort to avoid unnecessary morbidity among patients. Here, we review the literature on the laparosopic approach to the treatment of the adnexal mass without sacrificing the principles of oncologic surgery. We highlight potentials of minimally invasive surgery and address the risks associated with the laparoscopic approach.
UI - 93004879
AU - Markman M
TI - Ethical difficulties with randomized clinical trials involving cancer patients: examples from the field of gynecologic oncology.
SO - J Clin Ethics 1992 Fall;3(3):193-5
AD - Cleveland Clinic Cancer Center, Ohio.
UI - 21230506
AU - You Z; Fischer DC; Tong X; Hasenburg A; Aguilar-Cordova E; Kieback DG
TI - Coxsackievirus-adenovirus receptor expression in ovarian cancer cell lines is associated with increased adenovirus transduction efficiency and transgene expression.
SO - Cancer Gene Ther 2001 Mar;8(3):168-75
AD - Department of Obstetrics and Gynecology, Freiburg University Medical Center, Germany.
The expression of coxsackievirus-adenovirus receptor (CAR) and the integrins alpha(v)beta3 and alpha(v)beta5 was analyzed quantitatively (flow cytometry) and qualitatively (immunocytochemistry) in five human ovarian cancer cell lines (PEO1, PEO4, PEO14, SKOV-3, and OVCAR-3) and three control cell lines (293, HeLa, and CHO-K1). The transduction efficiencies were evaluated by adv/rsv-beta-Gal transduction followed by X-gal staining. The effects of 17beta-estradiol on cell growth, CAR and integrins alpha(v)beta3/5 expression, adenovirus transduction efficiency, and cell-killing efficacy of adv/rsv-tk plus ganciclovir were determined. The levels of CAR, integrin alpha(v)beta3, and integrin alpha(v)beta5 showed great variation between the cell lines. Whereas the expression of CAR appeared to be essential for and positively correlated with adenovirus transduction efficiency, the integrins alpha(v)beta3 and alpha(v)beta5 were not absolutely necessary for adenovirus transduction even though their presence may facilitate transduction. In PEO4 and PEO1 cells, proliferation was stimulated by 17beta-estradiol in a dose-dependent manner. In PEO4 cells, and much less pronounced in PEO1 cells, this was accompanied by an increase in CAR expression. The stimulation of CAR expression was paralleled by an increased transduction efficiency resulting in an increased cell-killing efficacy. Our data suggest that the expression of CAR is one of the most important prerequisites for successful adenovirus-mediated gene therapy of ovarian cancer.
UI - 21436589
AU - Kikuchi Y
TI - [The mechanism of cisplatin-resistance in ovarian cancer]
SO - Hum Cell 2001 Jun;14(2):115-33
AD - Department of Obstetrics and Gynecology, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama 359-8513, Japan. QWL04765@nifty.ne.jp
Cisplatin and its analogues have been most frequently used for treatment of human cancer including ovarian cancer. Most advanced ovarian cancer which was fatal before introduction of cisplatin have become to be treated for cure by combination chemotherapy containing cisplatin and its analogues. Thus, combination chemotherapy containing cisplatin and carboplatin have become a standard chemotherapy for treatment of ovarian cancer. Initially, platinum-based combination chemotherapy is associated with a 60-70% clinical response rate. However, the overall 5-year survival rate for advanced ovarian cancer patients is still around 20-30%. This low survival rate is due to the fact that some primary tumors and most recurrent tumors develop drug resistance that leads to treatment failure. Thus, overcoming drug resistance is the key to successful treatment of ovarian cancer. The mechanism of cisplatin-resistance in ovarian cancer is multifactorial, and accumulation of multiple genetic changes may lead to the drug-resistant phenotype. In this review, we report several genetic factors conferring cisplatin-resistance which have been elucidated in our laboratory.
UI - 21432004
AU - Hemminki A; Belousova N; Zinn KR; Liu B; Wang M; Chaudhuri TR; Rogers
TI - BE; Buchsbaum DJ; Siegal GP; Barnes MN; Gomez-Navarro J; Curiel DT; Alvarez RD An adenovirus with enhanced infectivity mediates molecular chemotherapy of ovarian cancer cells and allows imaging of gene expression.
SO - Mol Ther 2001 Sep;4(3):223-31
AD - The Gene Therapy Center, Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, AL 35294, USA. firstname.lastname@example.org
The adenovirus (Ad) is a useful vector for cancer gene therapy due to its unparalleled gene transfer efficiency to dividing and quiescent cells. Primary cancer cells, however, often have highly variable or low levels of the requisite coxsackie-adenovirus receptor (CAR). Also, assessment of gene transfer and vector persistence has been logistically difficult in human clinical trials. We describe here two novel bicistronic adenoviral (Ad) vectors, AdTKSSTR and RGDTKSSTR, which contain the herpes simplex virus thymidine kinase gene (TK) for molecular chemotherapy and bystander effect. In addition, the viruses contain the human somatostatin receptor subtype-2 gene (SSTR2), the expression of which can be noninvasively imaged. We enhanced the infectivity of RGDTKSSTR by genetically incorporating the RGD-4C motif into the HI-loop of the fiber. This allows the virus to circumvent CAR deficiency by binding to alpha(v)beta(3) and alpha(v)beta(5) integrins, which are highly expressed on most ovarian cancers. The expanded tropism of RGDTKSSTR results in increased infectivity of purified primary ovarian cancer cells and allows enhanced gene transfer in the presence of malignant ascites containing anti-Ad antibodies. RGDTKSSTR may be a useful agent for treating ovarian cancer in clinical trials.
UI - 21451018
AU - McDonnel AC; Murdoch WJ
TI - High-dose progesterone inhibition of urokinase secretion and invasive activity by SKOV-3 ovarian carcinoma cells: evidence for a receptor-independent nongenomic effect on the plasma membrane.
SO - J Steroid Biochem Mol Biol 2001 Aug;78(2):185-91
AD - Reproductive Biology Program, Department of Animal Science, University of Wyoming, Laramie 82071, USA.
Urokinase plasminogen activator (uPA) has been implicated in the metastatic potential of ovarian carcinomas of surface epithelial origin. The SKOV-3 human ovarian cancer cell line was tested for uPA secretory responses (enzyme immunoassay of conditioned media) after treatments with sex steroids, human menopausal gonadotropins (hMG), or gonadotropin-releasing hormone (GnRH). Secretion of uPA during a 6-h incubation was unaffected by testosterone, estradiol-17beta, hMG, or GnRH. Progesterone, at supraphysiological concentrations, suppressed uPA secretion; this reaction was not altered by the progesterone receptor antagonist RU486 or the transcriptional inhibitor actinomycin D. It appears that progesterone exerted a direct biophysical effect on the plasma membrane manifested by an interference with shedding of uPA in exocytotic vesicles. Finally, invasion of SKOV-3 cells into Matrigel was inhibited by progesterone. We suggest that progesterone can disrupt the fluid dynamics of plasma membranes and thereby invoke an antitumorigenic action via inhibition of proteolytic secretions.
UI - 21489946
AU - Cure H; Bay JO; Plagne R; Chollet P; Dauplat J
TI - [High-dose chemotherapy in advanced epithelial ovarian cancer]
SO - Bull Cancer 2001 Sep;88(9):842-51
AD - Centre Jean-Perrin, 58, rue Montalembert, BP 392, 63011 Clermont-Ferrand.
Since more than thirty years, ovarian cancer is wellknown to be chemosensitive. However, long term results of advanced stages remain low with 5 years overall survival around 20%. That's why high-dose chemotherapy in this chemosensitive disease has to be considered. Here, authors report the french, european and american experiences in three clinical settings: first in consolidation after complete or very good partial response, second after relapse or for refractory disease, third as first line treatment to increase clinical and pathological complete responses and improve prognosis. The more promising results concern high-dose chemotherapy as consolidation setting. The preliminary results of the french multicentric randomized phase III study (high-dose versus conventional dose) gives a favorable trend for high-dose approach as consolidation. This unique trial would definitively establish the place of high-dose chemotherapy in the first line treatment of advanced epithelial ovarian cancer.
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