National Cancer Institute®
Last Modified: May 1, 2002
UI - 11962511
AU - Talarico T; Cullinane C M; Gray P J; Webster L K; Deacon G B; Phillips D
TI - R Nuclear and mitochondrial distribution of organoamidoplatinum(II) lesions in cisplatin-sensitive and -resistant adenocarcinoma cells.
SO - Anticancer Drug Des 2001 Apr-Jun;16(2-3):135-41
AD - Victorian Cancer Cytogenetics Service, St Vincent's Hospital, Fitzroy, Australia.
The DNA binding pattern of the organoamidoplatinum(II) compound 1a is of considerable interest because of its known activity against cisplatin-resistant cells. The activity of 1a appears to be due at least in part to a greater cellular uptake than cisplatin into cisplatin-resistant cells, but little is known of the DNA reactions of the organoamidoplatinum(II) compounds. In this study the level of DNA cross-linking and total DNA lesions formed by 1 a were measured by gene-specific Southern hybridization cross-linking assays and by quantitative PCR in cisplatin-sensitive (2008) and in cisplatin-resistant 2008/R human adenocarcinoma cell lines. The surprising result was that the major difference between cisplatin and 1a was that the number of interstrand cross-links induced by 1a were approximately 5-fold greater than that induced by cisplatin in the nuclear (but not mitochondrial) DNA of resistant cells, even though the total number of lesions were essentially the same in both sensitive and resistant cells. This result suggests that the extent of interstrand cross-linking is a critical determinant of the cellular response to 1a and that the enhanced uptake of 1a into resistant cells results in this elevated level of cross-linking, leading to good activity of 1a against cisplatin-resistant cells. It remains unclear as to why 1a exhibits such selective damage to nuclear DNA, and insight into the molecular aspects of this selectivity will provide new opportunities for the further development of new platinum-based agents with activity against cisplatin-resistant cells.
UI - 11606393
AU - Kumar A; Soprano DR; Parekh HK
TI - Cross-resistance to the synthetic retinoid CD437 in a paclitaxel-resistant human ovarian carcinoma cell line is independent of the overexpression of retinoic acid receptor-gamma.
SO - Cancer Res 2001 Oct 15;61(20):7552-5
AD - Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Treatment of ovarian carcinomas with the antimitotic antitumor drug paclitaxel is highly efficacious. However, development of drug resistance presents a major obstacle. The common cellular phenotypes associated with paclitaxel resistance are an increased expression of the drug transport protein P-glycoprotein (P-gp), an alteration in the levels of beta-tubulin isotypes, and/or changes in the drug binding affinity of the microtubules. We established two paclitaxel-resistant human ovarian carcinoma cell lines. The 2008/17/4 cells exhibited a "classic" multidrug-resistant phenotype (overexpression of P-gp associated with cross-resistance to natural product drugs), whereas the 2008/13/4 cells were an atypical multidrug-resistant subline (no overexpression of P-gp). In addition to being paclitaxel resistant (250-fold), the 2008/13/4 cells were also cross-resistant to etoposide (39-fold) and vincristine (460-fold). To identify the alterations in the gene expression profile associated with the development of atypical paclitaxel resistance, we used the Clontech Atlas Human Cancer cDNA Microarray (spotted with 588 genes). The expression of retinoic acid receptor (RAR)-gamma was significantly higher in the paclitaxel-resistant (2008/13/4 and 2008/17/4) cells than in the parental (2008) cells. Northern blotting analysis demonstrated that the expression of RAR-gamma was 7-fold higher in the 2008/13/4 and 2008/17/4 cells than in the 2008 cells, whereas the expression of RAR-alpha and RAR-beta was not observed in any cell line. Whereas the 2008, 2008/13/4, and 2008/17/4 cells were found to resist the antiproliferative effects of all-trans-retinoic acid, the paclitaxel-resistant cells were 6- to 7-fold cross-resistant to the antiproliferative effects of CD437 (a synthetic RAR-gamma-selective agonist; 6-[-(1-admantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid) compared with the sensitivity of the parental cells. To further understand the association of paclitaxel and CD437 resistance with the observed RAR-gamma overexpression, we transfected the 2008 cells with a full-length RAR-gamma cDNA construct. Two transfectants with increased expression of the RAR-gamma mRNA and protein were isolated and subjected to growth inhibition assays in the presence of various concentrations of paclitaxel, etoposide, vincristine, and CD437. The sensitivity of the 2008 transfected clones (displaying increased expression of RAR-gamma) to the cytotoxic effects of paclitaxel, etoposide, vincristine, and CD437 was similar to that observed in the parental 2008 cells. These results suggest that the overexpression of RAR-gamma (observed in the 2008/13/4 and 2008/17/4 cells) by itself is not capable of inducing paclitaxel and CD437 resistance (or resistance to etoposide and vincristine).
UI - 11818204
AU - van den Bent MJ; van Putten WL; Hilkens PH; de Wit R; van der Burg ME
TI - Retreatment with dose-dense weekly cisplatin after previous cisplatin chemotherapy is not complicated by significant neuro-toxicity.
SO - Eur J Cancer 2002 Feb;38(3):387-91
AD - Department of Neuro-Oncology, Daniel den Hoed Cancer Clinic/University Hospital Rotterdam, PO Box 5201, 3008 AE, Rotterdam, The Netherlands. firstname.lastname@example.org
Cisplatin induces a cumulative dose-dependent axonal sensory neuropathy. With a cumulative dose over 600 mg/m2, a significant percentage of patients will develop a moderate or severe neuropathy. We retreated patients with progressive or recurrent ovarian cancer after previous platinum-containing chemotherapy with weekly 50-70 mg/m2 cisplatin for six cycles. This group was prospectively followed for the development of neuropathy. Patients received six weekly cycles of either 50 or 70 mg/m2 cisplatin, combined with oral etoposide. Responding patients continued treatment with daily oral etoposide for nine months. Neurological toxicity was assessed with a sensory sum score, the sensory neuropathy common toxicity criteria (CTC) and quantitated sensory analysis of the vibration perception threshold (VPT). Neurological assessment was scheduled at baseline, after three cycles, at the end of cisplatin chemotherapy and at 3 monthly intervals until 1 year after the discontinuation of chemotherapy. The first evaluation carried out in the interval of 1-4 months after the end of weekly cisplatin therapy was taken as the principle evaluation for neurotoxicity because during this time interval the nadir of cisplatin neurotoxicity is to be expected. Of 89 patients evaluated for neurological toxicity, 80 patients were fully evaluable. Forty-nine had received prior cisplatin (median cumulative dosage 450 mg/m2); the others had received prior treatment with carboplatin. Cisplatin pretreated patients had slightly higher neuropathy scores at the start of weekly cisplatin. Almost all cisplatin pretreated patients received six cycles of cisplatin, 29 at 50 mg/m2 and 20 at 70 mg/m2 per cycle. Despite treatment up to an overall cumulative dose of 750-900 mg/m2 cisplatin, only 1 patient discontinued treatment due to neurotoxicity. One other patient developed a grade 3 neuropathy during follow-up. Only a marginal increase of neuropathic signs and symptoms were observed in all the other patients. In multiple regression analysis, the increase in VPT or the sensory sum score was not related to prior treatment (cisplatin or carboplatin). Patients with mild signs of neuropathy after prior treatment with cisplatin to a cumulative dose level of 400-450 mg/m2 can be retreated with weekly cisplatin to a cumulative dose of 420 mg/m2 (overall cumulative dose up to 800-900 mg/m2) with only a minimal risk of significant neurotoxicity.
UI - 11929843
AU - Garattini E; Gianni' M; Terao M
TI - Correspondence re: A. Kumar et al., cross-resistance to the synthetic retinoid CD437 in a paclitaxel-resistant human ovarian carcinoma cell line is independent of the overexpression of retinoic acid receptor-gamma. Cancer Res., 61: 7552-7555, 2001.
SO - Cancer Res 2002 Apr 1;62(7):2192-3; discussion 2193-4
UI - 11935302
AU - Huober J; Meyer A; Wagner U; Wallwiener D
TI - The role of neoadjuvant chemotherapy and interval laparotomy in advanced ovarian cancer.
SO - J Cancer Res Clin Oncol 2002 Mar;128(3):153-60
AD - University of Tuebingen, Dept. of Gynecology and Obstetrics, Schleichstrasse 4, 72076 Tuebingen, Germany. email@example.com
Radical debulking surgery allows for optimal cytoreduction in less than 50% of patients with advanced ovarian cancer. In spite of highly efficient chemotherapeutic regimens, the prognosis of patients with residual tumor masses larger than 1 cm in diameter following staging laparotomy is very poor. This observation led to the initiation of numerous trials evaluating the feasibility and efficiency of the use of primary chemotherapy followed by interval laparotomy in women with advanced ovarian cancer. The available data is presented and discussed in this review.
UI - 11883295
AU - Bidzinski M; Krynicki R; Lindner B; Sobiczewski P; Panek G; Wierzba W;
TI - Lewandowski Z [Granulosa cell tumor--the assessment of some clinical and therapeutic parameters as prognostic factors]
SO - Ginekol Pol 2001 Dec;72(12A):1449-54
AD - Kliniki Nowotworow Narzadow Plciowych Kobiecych Centrum Onkologii w Warszawie.
The results of the clinical and therapeutic factors in prognostic mean was presented. 48 cases of granulosa cell tumours treated from 1984 to 1994 in Oncology Centre in Warsaw were analysed. In investigated group 13 patients died, but only 8 because of relapse of the tumour. Among all analysed patients, 79% have reached 5 years free survival period. Tumour rupture, FIGO stage and incidence of irregular bleeding before recognition of the tumour had significant prognostic value. There were surprising that relative risk of relapse between patients stage I and II were similar (1.0 vs 1.01). The relative risk between I and III stage had strong prognostic difference. Additional operation after no radical surgery did not influence on better prognosis, but followed radiotherapy increase treatment results.
UI - 11925132
AU - Gordon AN; Hancock KC; Matthews CM; Messing M; Stringer CA; Doherty MG;
TI - Teneriello M Phase I study of alternating doublets of topotecan/carboplatin and paclitaxel/carboplatin in patients with newly diagnosed, advanced ovarian cancer.
SO - Gynecol Oncol 2002 Apr;85(1):129-35
AD - Texas Oncology, P.A., Charles A. Sammons Cancer Center, Dallas, Texas 75246-2044, USA. firstname.lastname@example.org
OBJECTIVE: The aim of this study was to evaluate topotecan with carboplatin in an alternating doublet with carboplatin and paclitaxel in first-line ovarian cancer. METHODS: Patients with newly diagnosed stage III/IV ovarian cancer were studied. The maximum tolerated dose (MTD) of topotecan (cycles 1, 3, 5, 7) in an alternating doublet regimen was determined through standard dose escalation in cohorts of three; doses of carboplatin (area under the curve [AUC] 4 to 5) and paclitaxel (175 mg/m(2), cycles 2, 4, 6, 8) were fixed. Dose-limiting toxicity (DLT) was defined only for cycle 1 as febrile neutropenia, prolonged grade 4 granulocytopenia, grade 4 thrombocytopenia, > or =grade 3 nonhematologic toxicity, or failure to recover in < or =7 days. The use of granulocyte colony-stimulating factor (G-CSF) to permit further dose escalation was also studied. RESULTS: Thirty-seven patients received 142 cycles of topotecan/carboplatin. Hematologic DLTs included grade 4 neutropenia (59 events, 42% of cycles) and thrombocytopenia (32 events, 23% of cycles). Granulocytopenia was generally short-lived, and only 2 cases of febrile neutropenia occurred. The MTD was 1.0 mg/m(2)/day topotecan and carboplatin AUC 4, alternating with 175 mg/m(2) paclitaxel and carboplatin AUC 4. Although G-CSF effectively managed myelosuppression, thrombocytopenia developed in later cycles, limiting further topotecan dose escalation. The median progression-free survival was 20.5 months, and elevated pretreatment CA-125 levels normalized in 29 of 34 (85%) patients. CONCLUSION: The establishment of a reasonably well-tolerated alternating doublet regimen, coupled with evidence of antitumor activity, provides the basis for further investigation of topotecan in first-line therapy of ovarian cancer. Topotecan (1.0 mg/m(2) daily for 3 days) was chosen for further evaluation in a phase II study.
UI - 11925133
AU - Rose PG; Rodriguez M; Walker J; Greer B; Fusco N; McGuire W
TI - A phase I trial of prolonged oral etoposide and liposomal doxorubicin in ovarian, peritoneal, and tubal carcinoma: a gynecologic oncology group study.
SO - Gynecol Oncol 2002 Apr;85(1):136-9
AD - Division of Gynecologic Oncology, Case Western Reserve University, Cleveland, Ohio 44109, USA.
OBJECTIVES: In an effort to explore second-line therapy in ovarian, peritoneal, and tubal carcinoma, a phase I trial combining prolonged oral etoposide and liposomal doxorubicin was conducted by the Gynecologic Oncology Group. METHODS: Liposomal doxorubicin (20 mg/m(2)) was administered intravenously over 1 h followed by oral etoposide at 50 mg/m(2)/day beginning on day 2. In the first phase of accrual, the number of days of oral etoposide was increased until its maximum tolerated dose (MTD) was determined based on hematologic toxicity. In the second phase, etoposide was given at the MTD while the dose of liposomal doxorubicin was escalated until its maximum tolerated dose was reached based on hematologic or nonhematologic toxicity. Cycles were repeated every 28 days for a maximum of 12 courses. Dose-limiting toxicity was defined as neutropenic sepsis, grade 4 thrombocytopenia, absolute neutrophil count <1000/microl or platelets <50,000 during treatment with etoposide, or > or =grade 3 mucositis/stomatitis, palmar-plantar erythrodyesthesia, or rash. RESULTS: Fifteen patients were accrued to the study's first phase, and 3 were accrued to the second phase. Dose-limiting hematologic toxicity occurred with 14 days of oral etoposide in combination with liposomal doxorubicin at 20 mg/m(2). Efforts to escalate the dose of liposomal doxorubicin to 30 mg/m(2) in combination with 12 days of oral etoposide at 50 mg/m(2) resulted in dose-limiting hematologic toxicity. Five of 17 (29%; 95% CI: 13-53%) evaluable patients experienced a response. CONCLUSION: The regimen of oral etoposide at 50 mg/m(2)/day for 12 days in combination with liposomal doxorubicin at a dose of 20 mg/m(2) is tolerable without supportive therapy. While this dose of oral etoposide has demonstrated activity as a single agent in ovarian cancer, liposomal doxorubicin has only been effective in ovarian cancer at higher doses. There are no immediate plans to study this combination further.
UI - 11925118
AU - Fei R; Shaoyang L
TI - Combination antigene therapy targeting c-myc and c-erbB(2) in the ovarian cancer COC(1) cell line.
SO - Gynecol Oncol 2002 Apr;85(1):40-4
AD - Department of Gynecologic Oncology, Zhongnan Hospital, Wuhan University, 169 Donghu Road, Wuhan, 430071, People's Republic of China.
OBJECTIVE: Antigene therapy targeting only one oncogene in ovarian cancer has made much progress, although it still has some limitations. To explore the potential for combination antigene therapy in ovarian cancer, we examined the in vitro effects of liposmal antisense phosphorothioate oligodeoxynucleotides targeting c-erbB(2) and c-myc (LF-c-erbB(2)/c-myc AS-ODNs) in the human ovarian cancer COC(1) cell line. METHODS: COC(1) cells were treated differently as follows: group A with single LF-c-erbB(2) AS-ODNs; group B with single LF-c-myc AS-ODNs; group C with combination LF-c-erbB(2)/c-myc AS-ODNs; and group D as untreated control. Cell proliferation was studied by MTT assay and clonal cultures. RT-PCR was used to measure gene expression of c-erbB(2) and c-myc before and after transfection. Morphologic changes in the COC(1) cells were observed with the electron microscope. RESULTS: Single antigene therapy targeting c-erbB(2) or c-myc could reduce target gene expression and inhibit COC(1) cell growth by 61.9 +/- 9.3 and 64.5 +/- 11.2%, respectively. However, combination antigene therapy could not only suppress expression of c-erbB(2) and c-myc simultaneously, but also inhibit COC(1) cell proliferation with a higher inhibitory rate of 82.6 +/- 12.1%. Apart from that, the combination agents could induce COC(1) cell apoptosis. CONCLUSIONS: Our study suggests that combination antigene therapy targeting c-erbB(2) and c-myc can inhibit COC(1) cell proliferation and gene expression of c-erbB(2) and c-myc. Furthermore, its effectiveness is much higher than that of individual antigene therapy.
UI - 11925123
AU - Covens A; Carey M; Bryson P; Verma S; Fung Kee Fung M; Johnston M
TI - Systematic review of first-line chemotherapy for newly diagnosed postoperative patients with stage II, III, or IV epithelial ovarian cancer.
SO - Gynecol Oncol 2002 Apr;85(1):71-80
AD - University of Toronto, Ontario, Canada. email@example.com
OBJECTIVE: The aim of this study was to determine the optimal postoperative chemotherapy regimen for women with newly diagnosed stage II, III (micro or macro), or IV epithelial ovarian cancer. METHODS: A systematic search was conducted to find randomized controlled trials and published meta-analysis found that, compared with non-platinum-based regimens, platinum, alone or in combination with other agents, improved survival when used as first-line chemotherapy for ovarian cancer. The meta-analysis did not detect a difference in efficacy between cisplatin and carboplatin. A published randomized trial of cisplatin plus paclitaxel versus carboplatin plus paclitaxel did not detect a significant difference in survival between these regimens. In two randomized trials, treatment with paclitaxel plus cisplatin resulted in improved survival compared with cyclophosphamide plus cisplatin. A randomized trial of paclitaxel plus cisplatin versus paclitaxel alone versus cisplatin alone detected no differences in survival among the three treatment groups. While hematologic adverse effects were more frequent with carboplatin than with cisplatin, nonhematologic adverse effects were less frequent with carboplatin. The addition of paclitaxel to cisplatin did not appear to increase the incidence of serious adverse effects. CONCLUSIONS: Intravenous carboplatin plus paclitaxel is the recommended postoperative chemotherapy regimen for newly diagnosed stage II-IV epithelial ovarian cancer. Intravenous cisplatin plus paclitaxel may also be considered a treatment option. Intravenous carboplatin as a single agent may be considered a treatment option in patients for whom paclitaxel is contraindicated or in patients who are unwilling to accept the adverse effects of paclitaxel chemotherapy.
UI - 11937008
AU - Kaye SB
TI - Combination chemotherapy for ovarian cancer--lessons not yet learned?
SO - Curr Oncol Rep 2002 May;4(3):185-6
AD - CRC, Department of Medical Oncology, Royal Marsden Hospital, Downs Road, Surrey SM2 SPT, Sutton, UK. firstname.lastname@example.org
UI - 11985374
AU - Anonymous
TI - Management of advanced-stage ovarian cancer: median survival rate about 2-3 years.
SO - Prescrire Int 2002 Feb;11(57):24-5
(1) Most cases of ovarian cancer are diagnosed at an advanced stage (peritoneal extension beyond the pelvis or distant metastases). (2) The standard treatment is surgery followed by chemotherapy with paclitaxel + platinum salt. Data favouring carboplatin over cisplatin in this setting are of poor quality. (3) There is no standard second-line chemotherapy regimen.
UI - 11859726
AU - Li H; Liu L; Zhang W
TI - [Single topotecan or in combination with other chemotherapeutic agents for 18 recurrent advanced ovarian cancer patients]
SO - Zhonghua Zhong Liu Za Zhi 2001 Nov;23(6):513-5
AD - Department of Gynecologic Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
OBJECTIVE: This study was designed to evaluate the efficacy and toxicity of topotecan hydrochloride, used singly or combined with other drugs in patients with recurrent advanced ovarian cancer. METHODS: Eighteen ovarian cancer patients who had received cytoreductive operation 1 to 3 times and 8 to 18 courses of chemotherapy but still failed in DDP-based(86.3%) and Taxol-based(32.7%) as well as combined DDP and Taxol-based(30.7%) chemotherapy, were divided into 3 groups: 1. Topotecan 1.2 mg/m2 q.d.i.v. for 5 consecutive days every 3 weeks for a total of 6 patients and 14 courses. 2. Topotecan 0.7 mg/m2 q.d.i.v. for 5 consecutive days and cis-platin 20 mg/m2 q.d.i.v. for 3 consecutive days over 4 weeks and 3. Topotecan 0.7 mg/m2 q.d.i.v. for 4 consecutive days and taxol 100 mg/m2 q.d.i.v. for one day as well as cis-platin 20 mg/m2 q.d.i.v. for 3 consecutive days totalling 12 patients and 27 courses. All together 18 courses, median 2.7 courses, were given. RESULTS: All 18 patients were evaluable. PR was achieved in 3 patients with a response rate of 16.7%. The main adverse effects were hematological toxicity, lasting for 3-27 days. Ten (55.6%) patients developed leucocytopenia Grade III-IV which occurred in 16(33.3%) courses. Six(33.3%) patients developed thrombocytopenia Grade III-IV which occurred in 8(16.7%) courses. Six(33.3%) patients developed RBC reduction Grade III which occurred in 8(16.7%) courses. Peripheral nerve inflammation was most serious in the non-hematologic toxicity. CONCLUSION: Topotecan is effective in recurrent advanced ovarian cancer patients who have failed in DDP or/and taxol-based regimes. Topotecan combined with cisplatin and taxol would be effective even if single topotecan has failed. Careful evaluation before treatment is indicated.
UI - 11966485
AU - Sayedur Rahman M; Al-Sibai MH; Rahman J; Al-Suleiman SA; El-Yahia AR;
TI - Al-Mulhim AA; Al-Jama F Ovarian carcinoma associated with pregnancy. A review of 9 cases.
SO - Acta Obstet Gynecol Scand 2002 Mar;81(3):260-4
AD - Department of Obstetrics, University of Garyounis, Benghazi, Libya. email@example.com
BACKGROUND: The purpose of this study was to review patients with ovarian cancer in pregnancy, the effectiveness of the available methods of treatment and their prognosis. METHODS: A retrospective review of all women diagnosed to have cancer of the ovary associated with pregnancy diagnosis, treatment, pregnancy outcome and maternal survival were noted. RESULTS: The incidence of ovarian carcinoma in pregnancy in the series was 0.08/1000 deliveries. Of the 9 patients, 7 had epithelial cancers; 4 serous cystadenocarcinoma, 2 mucinous cystadenocarcinomas and one undifferentiated cancer. One patient each had dysgerminoma and granulosa cell tumor. Six patients were in FIGO stage Ia, one Ic, one IIa. One patient was in stage III. Five patients were treated by unilateral salpingo-oophorectomy during pregnancy. Three patients had total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy followed by chemotherapy. Debulking of the tumor was done in a patient in stage III with subsequent chemotherapy. This patient died 13 months from the time of diagnosis of the tumor. The overall 5-year survival rate in the series was 78% and 100% for stage Ia. CONCLUSIONS: Association of ovarian cancer with pregnancy is a rare occurrence. Early diagnosis and appropriate treatment offers the best prognosis for the patient. The higher survival rates in the series was attributed to a larger number of patients in stage I of the disease and 2 patients with a germ cell tumor and dysgerminoma which have the best prognosis. Aggressive postoperative chemotherapy also contributed to the better outcome.
UI - 11899407
AU - Anastasia PJ
TI - Nursing considerations for managing topotecan-related hematologic side effects.
SO - Clin J Oncol Nurs 2001 Jan-Feb;5(1):9-13
AD - Paula.Anastasia@cshs.org
Topotecan (Hycamtin, SmithKline Beecham, Philadelphia, PA) was approved by the U.S. Food and Drug Administration in 1996 for use in relapsed ovarian cancer and in 1999 for platinum-sensitive small-cell lung cancer. Hematologic toxicity has been the predominant side effect associated with its use. Patients who have had extensive platinum-based therapy have exhibited increased degrees of thrombocytopenia and more severe neutropenia. These adverse events can be managed by identifying high-risk patients (i.e., those with more than six cycles of chemotherapy containing an alkylating agent or radiation to more than 25% of marrow-bearing bones, patients with a history of myelosuppression or renal impairment) and by recommending appropriate dose modifications based on the creatinine clearance measurement. By reducing the topotecan dose, myelosuppressive effects, as evidenced by neutropenia and thrombocytopenia, may be lessened or prevented without reducing the antitumor response.
UI - 11504529
AU - Sugarbaker PH
TI - Zang RY, Zhang ZY, Li ZT et al. Impact of secondary cytoreductive surgery on survival of patients with advanced epithelial ovarian cancer. Eur J Surg Oncol 2000; 26:798-804.
SO - Eur J Surg Oncol 2001 Aug;27(5):515-6
UI - 11845259
AU - Hernando JJ; Park TW; Kubler K; Offergeld R; Schlebusch H; Bauknecht T
TI - Vaccination with autologous tumour antigen-pulsed dendritic cells in advanced gynaecological malignancies: clinical and immunological evaluation of a phase I trial.
SO - Cancer Immunol Immunother 2002 Mar;51(1):45-52
AD - Department of Obstetrics and Gynaecology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. firstname.lastname@example.org
Dendritic cell (DC)-based therapy has proven to be effective in patients with malignant lymphoma, melanoma, and renal and prostate carcinoma. In this phase I clinical trial, we have shown that patients with advanced gynaecological malignancies can be effectively vaccinated with DC pulsed with keyhole limpet haemocyanin (KLH) and autologous tumour antigens. Two patients with uterine sarcoma and six subjects with ovarian carcinoma received three to 23 intracutaneous injections of antigen-pulsed DC at 10-day or 4-week intervals. Three patients showed stable disease lasting 25 to 45 weeks, and five experienced tumour progression within the first 14 weeks. KLH- and tumour lysate-specific delayed-type hypersensitivity (DTH) reactions were observed in six and one patient, respectively. Lymphoproliferative responses to KLH and to tumour lysate stimulation were recorded in six patients and in two patients respectively. Tumour antigen-stimulated interferon-gamma (IFN-gamma) secretion by peripheral blood mononuclear cells (PBMC) in one patient was consistent with a T(H) type 1 cytokine bias. The treatment was safe, well tolerated, immunologically active and except for local cutaneous hypersensitivity devoid of significant adverse effects.
UI - 11930694
AU - Wang J; Zhang W
TI - [Restaging laparotomy of presumed early ovarian cancer]
SO - Zhonghua Fu Chan Ke Za Zhi 2001 Nov;36(11):672-4
AD - Department of Gynecologic Oncology, Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100021, China.
OBJECTIVE: To assess the value and complications of restaging laparotomy in women with presumed early ovarian cancer who have undergone inadequate initial staging procedures. METHODS: Between 1986 and 1996, 42 patients underwent restaging laparotomy in Cancer Hospital, Peking Union Medical College after receiving inadequate initial surgical procedure for presumed early ovarian cancer. Presumed stages from initial surgery include stage I a in 28 cases; I b in 1 case; I c in 12 cases; II a in 1 case. Histological distributions were as follows: epithelial cancer in 26 cases; malignant germ cell tumor in 9 cases; granulose cell tumor in 7 cases. RESULTS: Twelve patients (28.6%) had disease upstaged and eight (19.0%) had stage III disease confirmed by restaging laparotomy. Positive findings at restaging laparotomy were mainly in omentum (16.7%) and pericolic gutters (33.3%). Peritoneal cytology was positive in 25.0 percent of patients. Three and five year survival rates for 30 patients with negative findings were 96.7% and 86.7%, respectively. Complications of restaging laparotomy included hemorrhage blood loss (50-1,100 ml, average 280 ml) and lymphocyst (7.1%). CONCLUSIONS: Patients with presumed early ovarian cancer who had undergone inadequate staging procedures should undergo restaging laparotomy. Patients with negative findings have an excellent prognosis. Complications of restaging laparotomy were minor.
UI - 11989902
AU - Pignata S; Di Maio M; Ottaiano A; De Maio E; Barletta E; Pisano C;
TI - Tambaro R Single agents or combination chemotherapy for advanced ovarian carcinoma in elderly patients: pro single agents.
SO - Tumori 2002 Jan-Feb;88(1 Suppl 1):S117-9
AD - Divisione di Oncologia Medica B, Istituto Nazionale Tumori, Fondazione G Pascale, Naples.
UI - 11989903
AU - Nicoletto O; Donach M; Crivellari G
TI - Polychemotherapy in ovarian cancer in patients over seventy years of age.
SO - Tumori 2002 Jan-Feb;88(1 Suppl 1):S120-1
AD - Divisione Oncologia Medica Azienda Ospedaliera, Padua.
UI - 11989921
AU - Repetto L; Pietropaolo M; Granata R; Ventura I; Gianni W
TI - Weekly paclitaxel infusion in elderly patients with solid tumors.
SO - Tumori 2002 Jan-Feb;88(1 Suppl 1):S39-40
AD - UO Oncologia INRCA, Rome.
UI - 11799032
AU - Kirwan JM; Tincello DG; Herod JJ; Frost O; Kingston RE
TI - Effect of delays in primary care referral on survival of women with epithelial ovarian cancer: retrospective audit.
SO - BMJ 2002 Jan 19;324(7330):148-51
AD - Liverpool Women's Hospital. email@example.com
OBJECTIVE: To examine referral pathways from primary care for patients with epithelial ovarian cancer and to identify factors related to survival at 18 months. DESIGN: Retrospective review of patient notes. SETTING: General practices and receiving hospitals within Mersey region. SUBJECTS: 135 patients with epithelial ovarian cancer identified from an audit in the Mersey area between 1992 and 1994. MAIN OUTCOME MEASURES: Delays between onset of symptoms and treatment attributable to patient, general practitioner, and hospital. RESULTS: 105 (78%) women first presented to their general practitioner within four weeks of the onset of symptoms. 99 (73%) women were referred to hospital by their general practitioners within four weeks of presentation, and 95 (70%) were seen in hospital within two weeks of referral. Multivariate analysis with survival as the dependent variable identified age (odds ratio 0.96, 95% confidence interval 0.93 to 0.99) cancer stage III or more (0.15, 0.05 to 0.43), and non-specific symptoms (0.36, 0.14 to 0.89) as significant variables. CONCLUSION: Most patients attended their general practitioner within four weeks and were referred within two weeks. No evidence was found that delays in referral or diagnosis adversely affected survival at 18 months. Stage of disease at surgery was the most important adverse factor. An effective screening programme is the most likely method to improve survival.
UI - 11839654
AU - Montazeri A; Culine S; Laguerre B; Pinguet F; Lokiec F; Albin N; Goupil
TI - A; Deporte-Fety R; Bugat R; Canal P; Chatelut E Individual adaptive dosing of topotecan in ovarian cancer.
SO - Clin Cancer Res 2002 Feb;8(2):394-9
AD - Institut Claudius-Regaud, 20-24 rue du Pont-St-Pierre, F-31052 Toulouse, France.
PURPOSE: To take into account relationships between topotecan area under the plasma concentration (AUC) versus time curve and percentage decrease of neutrophil count previously shown when topotecan is administered on a 5-day, daily schedule. A multicentric clinical trial with individualized dosing of topotecan was performed in patients with platinum-refractory ovarian cancer. The primary goal of this study was to evaluate the toxicity of topotecan when the interindividual variability in plasma drug exposure is decreased. EXPERIMENTAL DESIGN: A total of 39 patients were evaluable. In cycle 1, the daily dose for the last 2 days was dependent on the observed topotecan AUC at day 1; the general objective was to constrain the overall AUC (i.e., from day 1 to day 5) within 37,500-75,000 nM.min. A pharmacokinetic study was also performed on day 5 of cycle 1 and day 1 of cycle 2 to evaluate the intrapatient pharmacokinetic variability both within cycle 1 and between cycles. RESULTS: The dose of topotecan was decreased for 20 patients and increased for only 1 patient within cycle 1. The total administered dose was correlated to the creatinine clearance. The dose adjustments allowed control of the topotecan exposure: mean (+/-SD) observed AUC of 70,697 (+/-12,364) nM.min. Fourteen cases of dose-limiting toxicity were observed, mainly in patients who previously received two different regimens of chemotherapy without a washout period before topotecan treatment. An overall response rate of 21% was observed in the 33 patients evaluable. CONCLUSION: Dose adjustments are required not only in patients with creatinine clearance below 40 ml/min, but also in those with values between 40 and 60 ml/min (recommended starting dose is 1.2 mg/m(2)). By performing drug monitoring and taking into consideration the past treatment of each patient, better dose individualization can be obtained.
UI - 11981009
AU - Markman M; Hall J; Spitz D; Weiner S; Carson L; Van Le L; Baker M
TI - Phase II trial of weekly single-agent paclitaxel in platinum/paclitaxel-refractory ovarian cancer.
SO - J Clin Oncol 2002 May 1;20(9):2365-9
AD - Cleveland Clinic Taussig Cancer Center, Cleveland, OH 44195, USA. firstname.lastname@example.org
PURPOSE: We wished to critically examine the level of activity of weekly paclitaxel in a patient population with well-characterized platinum/paclitaxel-resistant (3-week schedule) ovarian cancer. PATIENTS AND METHODS: Eligibility criteria for this phase II trial included the following: ovarian and fallopian tube cancers or primary carcinoma of the peritoneum; prior initial therapy with platinum/paclitaxel; and failure to respond to treatment (progression or stable disease as best response), or a response duration of less than 3 months, or if the response was more than 3 months, retreatment with both agents required and failure to respond a second time or the response duration was less than 3 months. Measurable or assessable disease (CA-125 response criteria) was required. Patients received weekly paclitaxel (80 mg/m(2)) until disease progression, unacceptable toxicity developed, or they elected to discontinue treatment. RESULTS: Fifty-three patients (52 assessable for toxicity and 51 for response) were entered onto this multi-institution trial. Of 248 total cycles (887 doses), only 13 (1%) were modified (dose reduction or treatment delay) because of side effects. Therapy was discontinued in five patients because of toxicity (four because of peripheral neuropathy, and one because of painful fingernail beds). Thirteen patients (25%; 95% confidence interval, 13.5% to 37.5%) achieved an objective response (four by CA-125 criteria, and nine by > or = 50% reduction of measurable disease). CONCLUSION: Weekly paclitaxel (80 mg/m(2)) is generally well tolerated and is an active second-line regimen against ovarian cancer that has demonstrated resistance to platinum/paclitaxel delivered on an every-3-week schedule.
UI - 11904473
AU - Janni W; Rjosk D; Strobl B; Bergauer F; Linka F; Dimpfl T; Schindlbeck
TI - C; Rack B; Kaestner R; Sommer H [Chemotherapy-associated myelosuppression in gynecological oncology]
SO - Gynakol Geburtshilfliche Rundsch 2001;41(3):166-73
AD - 1. Frauenklinik, Klinikum der Ludwig-Maximilians-Universitat, Munchen, Deutschland. email@example.com
INTRODUCTION AND OBJECTIVE: A clinically important myelosuppression due to adjuvant chemotherapy is seen more frequently as dosage is intensified and new drugs are used. The assessment of the cytopenia expected is frequently hampered by a lack of directly comparable data. The aim of this study was to compare - in our own patient population - the chemotherapy-associated myelosuppression of four chemotherapeutic regimens used in gynecological oncology. METHODS: 79 patients with primary breast cancer and 26 patients with epithelial ovarian carcinoma underwent cytostatic treatment, and the associated myelosuppression was evaluated by the determination of cytopenia and the need for supportive therapy. The chemotherapy regimens investigated were CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), 5-fluorouracil 600 mg/m(2), 6xq3w), EC/CMF (epirubicin 90 mg/m(2), cyclophosphamide 600 mg/m(2), 4xq3w, followed by CMF, 3xq3w), DE (docetaxel 75 mg/m(2), epirubicin 90 mg/m(2), 6xq3w) and CC (cyclophosphamide 600 mg/m(2), carboplatin AUC 6, 6xq3w). RESULTS: The EC/CMF and DE regimens were used significantly more frequently for more advanced tumor stages, but there were no differences concerning tumor-dependent prechemotherapeutic myelosuppression. Hemopoiesis was most impaired in the CC group with a mean drop of serum hemoglobin of 1.5 g/dl to the end of the cytostatic treatment; correspondingly, most transfusions of concentrated erythrocytes were needed in this group. The strongest suppression of leukopoiesis was found in the DE group, with a mean drop in leukocyte counts of 6.2 x 10(3)/microliter per cycle; in this group, a mean of 7.6 ready-made syringes with 263 microgram Lenogastrim was used to stimulate leukopoiesis. The severest drop in the mean thrombocyte count, i.e. 171.7 x 10(3)/microliter, was found in the CC group. CONCLUSIONS: The CC regimen impairs thrombo- and erythropoiesis most, whereas the DE regimen causes marked leukopenia. The regimen with the smallest myelosuppression was CMF. No severe cytopenia-associated complications were detected in any of the cases investigated.
UI - 12013157
AU - Camatte S; Morice P; Pautier P; Atallah D; Duvillard P; Castaigne D
TI - Fertility results after conservative treatment of advanced stage serous borderline tumour of the ovary.
SO - BJOG 2002 Apr;109(4):376-80
AD - Gustave-Roussy Institute, Villejuif, France.
OBJECTIVE: To assess the fertility of patients treated conservatively for a Stage II or III borderline ovarian tumour. DESIGN: A retrospective study. SETTING: Gynaecological oncology department in a French anti-cancer centre. POPULATION: Seventeen patients treated with conservative management for a Stage II (n = 6) or III (n = 11) borderline ovarian tumour were followed up. Fifteen patients underwent a unilateral salpingo-oophorectomy (with contralateral cystectomy in six patients), one had unilateral cystectomy and one a bilateral cystectomy. Fourteen patients had non-invasive implants and three had invasive implants. MAIN OUTCOME MEASURES: Pregnancy rates and outcome. RESULTS: Eight pregnancies were observed in seven patients in a median delay of eight months following the surgical procedure. Six pregnancies were observed spontaneously, one occurred after an ovarian stimulation and one after an IVF procedure. None of these patients recurred under the form of invasive ovarian carcinoma on the spared ovary. Two patients (one with a non-invasive disease and one with an invasive one) had recurrence in the form of evolutive invasive implants, but neither woman died. CONCLUSION: Spontaneous pregnancy can occur after conservative treatment of advanced stage borderline tumour of the ovary (with non-invasive implants). Such management, performed in a close follow up of the patients, does not affect the overall survival. Conservative surgery could be proposed in patients with borderline tumour of the ovary and non-invasive peritoneal implants.
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