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NCI CANCERLIT® Search: Therapy of Ovarian Cancer - February 2002
National Cancer Institute®
Last Modified: February 1, 2002
Table of Contents
1
UI - 11778564
AU - Li X; Liu L; Wu L
TI -
[Ifosfamide combination chemotherapy for advanced gynecologic
malignancies]
SO - Zhonghua Zhong Liu Za Zhi 2000 Jul;22(4):330-2
AD - Cancer Institute (Hospital), Peking Union Medical College, Chinese
Academy of Medical Sciences, Beijing 100021, China.
OBJECTIVE: To evaluate the clinical efficacy and toxicity of ifosfamide
(IFO) combination chemotherapy in patients with advanced gynecologic
malignancies. METHODS: Thirty-four patients with gynecologic
malignancies were included in this series. Of the 34 patients, 26 with
epithelial cancer of the ovary were previously treated with
cisplatin-containing combination chemotherapy but failed to respond or
recurred after treatment. They were treated with IEP (IFO, VP16, PDD)
regimen. The remaining 8 patients with uterine sarcoma (5 cases),
squamous-cell carcinoma of the uterine cervix with metastases to the
liver or bone (2 cases), and endometrial carcinoma with lung metastases
(1 case) were treated with IFO combination chemotherapy. At least two
courses of treatment were given unless tumor progression occurred after
the first course. RESULTS: The overall response rate was 35.3% including
8.8% complete response. The response rate of 26 patients with ovarian
cancer was 30.8%. Two patients with PDD-sensitive tumor all achieved
complete response, which lasted for one year. The response rate of the
remaining 24 PDD-resistant patients was 25% with a mean duration of 5.5
months. There was no complete response. Two patients with cervical
carcinoma and two of five patients with uterine sarcoma responded to IFO
combination chemotherapy. Relatively severe hematological toxicity was
observed, including grade III and IV leucopoenia and thrombocytopenia.
Two patients died from severe toxicity. CONCLUSION: IFO combination
chemotherapy is effective in treating recurrent or progressive
gynecologic malignancies, especially PDD-sensitive ones.
Myelosuppression is relatively severe which may be due to prior long
term and intensive chemotherapy.
2
UI - 11521789
AU - Boccardo F; Miglietta L; Bruzzone M; Rubagotti A; Locatelli MC; Ragni N
TI -
Paclitaxel plus organoplatins: still the gold standard in advanced
ovarian cancer?
SO - Ann Oncol 2001 Jul;12(7):1023-4
3
UI - 11791820
AU - McCann S; MacAuley D
TI -
Management of familial breast and ovarian cancer cases.
SO - Br J Gen Pract 2002 Jan;52(474):57
4
UI - 11769669
AU - Zhang A; Lu Y; Wang S
TI -
[Relationship between the expression of connexin 43 and bystander effect
of suicide gene therapy in ovarian cancer]
SO - Zhonghua Fu Chan Ke Za Zhi 2001 Sep;36(9):542-5
AD - Department of Obstetrics and Gynecologic, Tongji Hospital, Tongji
Medical College, Huazhong Science and Technology University, Wuhan
430030, China.
OBJECTIVE: To explore the relationship of connexin 43(Cx43) and
bystander effect in ovarian tumor cells in herpes simplex virus
thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy in vitro, and to
investigate the effection of all-trans retinoic acid (RA) on expression
of Cx43 and bystander effect. METHODS: Cx43 expression was examined with
flowcyto-metry, Western Blot, and immunofluorescence in two ovarian
tumor cells OVCAR3, CAOV3 before and after RA treatment. Bystander
effect was determined by the cells growth inhibitory rate with methyl
thiazolyl tetrazolium. RESULTS: Following exposure to ganciclovir, there
was much greater bystander killing in OVCAR3 than in CAOV3 (P < 0.05).
The expression of Cx43 was detected in OVCAR3 with flowcytometry and
Wstern Blot, but it could not be detected in CAOV3. The expression of
Cx43 in both cell lines could be induced by RA. Immunofluorescence
staining showed that OVCAR3 Cx43 protein is located in membrane surface,
whereas CAOV3 is in cytoplasm. RA could not change the location of Cx43
protein in both cell lines. CONCLUSIONS: There is relationship between
Cx43 expression and HSV-TK/GCV bystander effect. HSV-TK/GCV bystander
effect can be inhanced by RA in ovarian cancer.
5
UI - 11526698
AU - Zanetta G; Meni A; Brancatelli G; Chiari S; Lissoni AA; Ratti M; Buda A
TI -
[Comparison of methods for monitoring young women with stage I
borderline ovarian tumor after conservative surgery]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):10-1
AD - Istituto di Scienze Biomediche S. Gerardo Clinica Ostetrica e
Ginecologica, Universita degli Studi Bicocca, Milano.
6
UI - 11526699
AU - Balbi GC; Compagna R; Musone R; Cirelli G; Delli Ponti D; Cassese E;
TI -
Passaro M; Balbi F; Zarcone R
[Role of intestinal resection in primary cytoreduction of ovarian
cancer]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):100-1
AD - Istituto di Clinica Ostetrica e Ginecologica, Seconda Universita degli
Studi, Napoli.
BACKGROUND: The aim of this study is to define the role of the
intestinal removal for the therapy of ovarian cancer in advanced
stadium. METHODS: We have examined 247 females with epithelial ovarian
cancer in advanced stadium, that had intestinal removal. RESULTS: The
survival in the females that had a very good intestinal removal is
greatest than in the females that hadn't a very good intestinal removal.
7
UI - 11526701
AU - Balbi GC; Compagna R; Musone R; Cirelli G; Sgambato R; Cassese E; Delli
TI -
Ponti D; Passaro M; Zarcone R
[Cytoreductive surgery in patients with stage IV ovarian carcinoma]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):105-9
AD - Istituto di Clinica Ostetrica e Ginecologica, Seconda Universita degli
Studi, Napoli.
BACKGROUND: The aim of this study is to evaluate the efficacy of
cytoriductive surgical in females with ovarian carcinoma in advanced
stadium, and to define the role of this surgical for the survival of
females with hepatic metastases. METHODS: This is a retrospective study.
164 females with ovarian cancer in IV stadium was examined. 64 females
had hepatic metastasis. All patients had cytoriductive surgical.
RESULTS: The survival in the patients without hepatic metastasis was 38
months if the cytoreduction was very good; it was 18.3 months if there
is residual disease. The survival in the patients with hepatic
metastasis was 50.1 months if the cytoreduction was very good; it was 27
months if there is residual disease. CONCLUSIONS: A very good surgical
is very important for the survival of patients with ovarian cancer in
advanced stadium. This is true also in the patients with hepatic
metastases.
8
UI - 11526704
AU - Rampone B; Rampone A; Tirabasso S; Panariello S; Rampone N
TI -
Immunological variations in women suffering from ovarian cancer.
Influence of radical surgical treatment.
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):116-9
AD - Institute of Obstetrics and Gynaecology, Second University of Naples,
Italy.
BACKGROUND: The immune system includes all the innate or acquired
mechanisms, that the organism uses for protecting itself from the
aggression of external pathogens or neoplasia. About the control of the
tumor growth, the immune mechanisms implicated are quite a lot: the
cytotoxicity against the tumor cells by cytotoxic T lymphocyte,
macrophages, NK cells; simil-NK cells (ADCC). Tumors have generally
antigenic marked potential, for which numerous antigens have been
identified, but none of these has revealed a correlated specificity to
the neoplasia. Only a glycoprotein at elevated molecular weight, the
CA125, presents an elevated specificity and sensibility. The objective
of this study was to examine immunological variations in the peripheral
blood of patients with ovarian carcinoma before and after radical
surgical treatment. METHODS: In the Institute of Obstetrics and
Gynaecology of Second University of Studies of Naples the immunological
variations in 8 women (mean age: 59.5; range: 49-70 years) suffering
from ovarian cancer, have been evaluated before and after radical
surgical treatment (when the stage of the tumor made possible the
surgery) and compared to 8 normal volunteers of comparable age (control
in average for two years and subjected to a immunological screening with
blood drawings effected at the hospitalisation and later 1, 6, 12, 18,
24 months from surgical treatment. The immune evaluation were effected
with: proliferation tests on the monocytes of the peripheral blood,
evaluation of the production of Interleukin 1 and 2 with the leukocyte
phenotyping, evaluation of NK cells activity. The patients were followed
in average for two years. RESULTS: The radical surgery decidedly
improves the immune response. The ability to produce IL-1 by the
lymphocytes of the patients object of our study, appeared constantly
falling (with reduction of about 50%) before the surgery and it
meaningfully increases in the post-surgery period. The surgery doesn't
modify the lymphocytes T helper and T inducer. The surgery delays the
diminution of the NK cells in a little meaningful way. The periodic
dosage of the CA125 does not give the same results: in the 60% a
progressive increase was realised and in the 40% it remained constant.
CONCLUSIONS: The surgery constantly improved the physical state of the
patient, determining an increase of the immune response toward the
neoplasia, and therefore achieving a meaningful increase of survival.
9
UI - 11526711
AU - Russo A; Cirelli G; Cassese E; Delli Ponti D; Sgambato R; Cecere F;
TI -
Zarcone R
[Second-look in ovarian cancer: laparoscopy or laparotomy?]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):146-54
AD - Istituto di Ginecologia ed Ostetricia, Seconda Universita degli Studi di
Napoli. Alef2@wappi.com
BACKGROUND: The aim of the present study was to compare the laparoscopic
second-look with laparotomic second-look as regards the consistency of
diagnosis of residual tumoral disease after first step treatment in
patients affected by ovarian cancer, and to evaluate the feasibility of
the laparoscopic second-look. METHODS: Twenty-one patients affected by
ovarian cancer underwent laparoscopic second-look followed by
laparotomic second-look. Six months after the first surgical
intervention all the patients showed no contraindications to
laparoscopic second-look. All the surgeries were performed with the same
procedure: after the introduction of the trocars the lysis of adherences
was carried out, the whole abdominal cavity was explored, 18
abdominal-pelvic sites were examined, direct biopsies were performed and
samples for the cyto- and histological analysis were obtained. RESULTS:
Positive predictive value for laparoscopy was 100% (6 out of 6 cases),
while negative predictive value was 84% (2 false negative cases out of
12). The complete abdominal-pelvic examination was possible in 95% of
cases with laparotomy while in 41% of cases with laparoscopy, because of
post-operative severe adherences. CONCLUSIONS: Laparoscopic second-look
has a good consistency as regards the diagnosis of residual tumoral
disease, but its feasibility is lower than laparotomy owing to the
presence of severe adherences and the high risk of intra- and
post-operative compliances.
10
UI - 11526713
AU - Scarabelli C; Gallo A
TI -
[Second surgery of ovarian carcinoma]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):25-8
AD - Divisione di Oncologia Chirurgica Ginecologica, Centro di Riferimento
Oncologico di Aviano, Istituto Nazionale di Ricovero e Cura a Carattere
Scientifico, Aviano, Pordenone.
11
UI - 11526714
AU - Cortesi E; Martelli O; Padovani A
TI -
[Role of intraperitoneal chemotherapy]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):29-33
AD - Dipartimento di Medicina Sperimentale e Patologia, Universita degli
Studi di Roma La Sapienza, Roma.
12
UI - 11526716
AU - Frassinetti L
TI -
[Chemoresistance in antineoplastic treatment of ovarian tumors]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):34-6
AD - Dipartimento di Oncologia, ASL, Forli.
13
UI - 11526718
AU - Ferrandina G; Legge F; Fagotti A; Fanfani F; Mancuso S; Scambia G
TI -
[Biological factors with prognostic significance in ovarian cancer]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):40-5
AD - Istituto di Clinica Ostetrica e Ginecologica, Universita Cattolica del
Sacro Cuore, Roma.
14
UI - 11526723
AU - Bolis PF; Zanaboni F; Crotti S
TI -
[Borderline ovarian tumors]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):6-9
AD - Clinica Ostetrica e Ginecologica, Universita dell'Insubria, Sede vi
Varese.
15
UI - 11526725
AU - Ambrosio D; Piscopo L; Lauro C; Rotondi M; Gallo E; Balbi F
TI -
[Treatment of ovarian carcinoma with intraperitoneal administration of
interferon alpha 2b]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):67-71
AD - I Divisione Clinica Ostetrica e Ginecologica, Seconda Universita degli
Studi, Napoli.
BACKGROUND: Pharmacokinetic studies have confirmed that for many
chemotherapeutic agents a substantial pharmacological advantage can be
achieved using the intraperitoneal route. Aim of this study is to
evaluate the efficacy of intraperitoneal interferon alpha 2b
chemotherapy to treat ovarian cancer. METHODS: Forty-four patients
affected by ovarian cancer have been submitted to intraperitoneal
Gynecology and Obstetric Institute of the Second University of Naples.
Intraperitoneal route has been obtained through a catheter in left iliac
fossa. Drugs have been solved in 2000 ml of physiologic solution to
obtain a better distribution into the peritoneal fluid. RESULTS: Three
patients of 15 not-pre-medicated and 16 of 24 pre-medicated have
obtained complete anatomo-pathological resolution. No compliances have
been checked about catheter. Only two patients have stopped the therapy
for asthenia; all the others have well tolerated interferon.
CONCLUSIONS: Our study shows the very low toxicity of interferon
associated to a good tolerance of the intraperitoneal catheter and
therefore we retain that intraperitoneal chemotherapy with interferon
alpha 2b improves the prognosis of patients with minimal ovarian cancer
after systemical chemotherapy.
16
UI - 11526732
AU - Iervolino P; Palmieri M; Rotondi M; D'Alessandro P; Iuliano R
TI -
[Borderline ovarian tumors. Retrospective analysis of 20 cases]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):97-9
AD - Divisione di Ostetricia e Ginecologia, Ospedale S. Maria di Loreto
Nuovo, Napoli.
BACKGROUND: To evaluate the clinical features, the surgical management
and outcome of 20 patients with stage-I borderline ovarian tumors.
METHODS: Twenty cases of FIGO stage-I ovarian tumors, aged from 31 to 58
years (mean 37 years) have been reviewed. All informations of clinical
stage, surgical intervention and prognosis were achieved by reviewing
hospital records. Minimal requirements for conservative management were
adequate staging and complete information about the therapeutic options.
Factors important in the choice of the treatment were, age, wish to
preserve fertility, histologic type and grade, and the stage of the
tumour. RESULTS: Eleven of the 20 patients (55%) were at stage IA, 6
cases (30%) were at stage IB, 3 cases (15%) were at stage IC. Thirteen
(65%) were with mucinous cystadenoma of borderline malignancy, 7 cases
(35%) were of serous type. Thirteen patients underwent total abdominal
hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO). Seven
patients were treated with unilateral oophorectomy or unilateral
salpingo-oophorectomy (USO). One patient underwent enucleation of
ovarian tumor and biopsy of contralateral ovary. Any patient were
treated with chemotherapy after operation. With a median follow up of
two years, we observed no recurrence of carcinoma in women treated
conservatively or in those treated more radically. CONCLUSIONS:
Conservative surgery remains a therapeutic option in selected patients
with borderline ovarian tumors. Prolonged intensive follow-up is
required for women treated conservatively for borderline malignant
ovarian tumours.
17
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. john.kirwan@lwh-tr.nwest.nhs.uk
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.
18
UI - 11586410
AU - Kolesnikova AI; Sychenkova NI; Konoplyannikov AG; Lepekhina LA; Kal'sina
TI -
SS; Krikunova LI; Mardynskii YS
Effect of irradiation on colony-forming ability of stem cells from
patients with ovarian cancer.
SO - Bull Exp Biol Med 2001 Jun;131(6):570-2
AD - Medical Research Center for Radiology, Russian Academy of Medical
Sciences, Obninsk.
In patients with ovarian cancer, the colony-forming capacity and
radiosensitivity of clonogenic tumor cells from the primary node and
metastases (ascites) differed considerably.
19
UI - 11790279
AU - Snow PB; Brandt JM; Williams RL
TI -
Neural network analysis of the prediction of cancer recurrence following
debulking laparotomy and chemotherapy in stages III and IV ovarian
cancer.
SO - Mol Urol 2001 Winter;5(4):171-4
AD - Xaim, Inc., Colorado Springs, Colorado 80918, USA. psnow@xiam.com
An artificial neural network (ANN) has been developed to predict the
presence or absence of cancer following debulking laparotomy and
chemotherapy in patients with stages III and IV ovarian cancer. The
presence or absence of a residual gross tumor or microscopic disease was
determined by a second-look laparotomy. The ANN was trained and tested
using detailed operative findings and related surgical procedures
associated with the debulking surgery. The ANN predictive results were
compared with linear and logistic regression. The ANN significantly
outperformed both logistic and linear regression analyses, but
additional cases are needed to validate the network.
20
UI - 11825920
AU - McCluggage WG; Lyness RW; Atkinson RJ; Dobbs SP; Harley I; McClelland
TI -
HR; Price JH
Morphological effects of chemotherapy on ovarian carcinoma.
SO - J Clin Pathol 2002 Jan;55(1):27-31
AD - Department of Pathology, Royal Group of Hospitals Trust, Grosvenor Road,
Belfast BT12 6BL, Northern Ireland. glenn.mccluggage@bll.n-i.nhs.uk
AIMS: Traditionally, advanced stage ovarian carcinoma is treated by
debulking surgery followed by chemotherapy. However, in some
circumstances preoperative chemotherapy may be given before optimal
surgical debulking. This study aims to describe the morphological
features found in ovarian carcinoma after chemotherapy because these
have not been detailed previously. METHODS: Histological sections were
examined from 18 cases of ovarian carcinoma that had been treated by
preoperative chemotherapy. The morphology was compared with any
pre-chemotherapy biopsies that had been performed. Tumours were
classified as showing morphological features suggesting a good response
to chemotherapy (n = 14) or as showing little or no response (n = 4).
Serum CA125 values before and after chemotherapy were compared. In all
cases, the mitotic activity index (MAI), volume percentage of epithelium
(VPE), and mean nuclear area (MNA) of tumour cells were calculated.
RESULTS: The preoperative biopsies were all typical ovarian serous or
endometrioid adenocarcinomas. Morphological features present in the
group responding to chemotherapy included the presence of small groups
or single tumour cells in a densely fibrotic stroma. Tumour cells were
characterised by both nuclear and cytoplasmic alteration, making
accurate tumour typing and grading impossible. Nuclear features included
the presence of bizarre enlargement with hyperchromatism, irregularity
of outline, and chromatin clumping or smudging. Cytoplasmic alterations
included intense eosinophilia, vacuolation, or foam cell change. There
were pronounced stromal changes of fibrosis, inflammation, collections
of foamy histiocytes, cholesterol cleft formation, haemosiderin
deposition, fat necrosis, and dystrophic calcification, including the
presence of many free psammoma bodies. There was no correlation between
morphological response and biochemical response, as determined by serum
CA125 values. In all nine cases in which pre-chemotherapy and
post-chemotherapy biopsies were available, the MNA increased
post-chemotherapy (p = 0.007, paired Wilcoxon test) and in six of nine
cases the MAI decreased (p = 0.093). CONCLUSIONS: Because preoperative
chemotherapy is being used increasingly in the management of ovarian
cancer, pathologists should be aware of the resultant morphological
effects. Accurate tumour typing and grading is impossible. In some
cases, it may be difficult to confirm the presence of residual tumour,
making it imperative that pre-chemotherapy tissue biopsies are obtained.
Definite confirmation of residual tumour may require the examination of
multiple histological sections from areas showing pronounced stromal
changes, sometimes with multiple levels and immunohistochemistry. In the
absence of definite residual tumour, the report should state that the
features are consistent with the prior presence of tumour.
21
UI - 11833305
AU - Hamid D; Rohr S; Baldauf JJ; Ritter J; Kurtz E; Dufour P; Meyer P;
TI -
Minetti A; Meyer C
[Interest in intestinal resection for treatment of advanced ovarian
cancer]
SO - Ann Chir 2002 Jan;127(1):40-7
AD - Service de gynecologie-obstetrique I, hopitaux universitaires de
Strasbourg-Hautepierre, 1, avenue Moliere, 67200 Strasbourg, France.
AIM OF THE STUDY: Digestive surgery is often necessary for surgical
management of advanced ovarian carcinoma. PATIENTS AND METHODS: In a
series of 62 patients with stage III ovarian carcinoma, postoperative
morbidity and mortality, overall survival after 5 years and disease-free
survival after 2 years were studied and corelated with several patients
criteria (age, stage of the disease, residual disease, type of surgery,
CA125 normalisation delay, postoperative complications and hospital
stay). Patients were divided into two groups according to the surgical
treatment. The first group (n = 17) included patients treated by
gynecologic and digestive surgery, the second group (n = 45) included
patients treated by gynecologic surgery only. All patients were proposed
for chemotherapy included platyn salt. Mean age was 60 years (range:
20-83). The stage of the cancer was stage IIIa in 7 cases, stage IIIb in
ten and stage IIIc in 45. RESULTS: Postoperative mortality was 3.5%
(2/62). Postoperative morbidity was 26% (13/62). No statistical
differences were noted for hospital stay, general morbidity, surgical
morbidity when a gastric resection or a colon resections or a
splenectomy were performed. Overall survival at 5 years was 56%.
Residual disease less than 2 cm3 is the only prognostic factor for
overall survival (56% vs 23% [P = 0.03]) and disease-free survival (86%
vs 46% [P = 0.02]). CONCLUSION: This study including 62 patients
confirmed the prognostic significance of extensive cytoreductive surgery
for treatment in advanced ovarian epithelial cancer without increasing
the postoperative morbidy and mortality.
22
UI - 11583193
AU - du Bois A; Luck HJ; Pfisterer J; Schroeder W; Blohmer JU; Kimmig R;
TI -
Moebus V; Quaas J
Second-line carboplatin and gemcitabine in platinum sensitive ovarian
cancer--a dose-finding study by the Arbeitsgemeinschaft Gynakologische
Onkologie (AGO) Ovarian Cancer Study Group.
SO - Ann Oncol 2001 Aug;12(8):1115-20
AD - Department of Gynecology, Dr.-Horst-Schmidt-Kliniken Wiesbaden, Germany.
dubois.hsk-wiesbaden@uumail.de
BACKGROUND: Despite the progress that has been achieved in the last
years, recurrence rates in ovarian cancer patients are still
considerably high and the majority of patients ultimately become
candidates for second-line treatment. Carboplatin reinduction is a
broadly adopted regimen in patients with recurrences occurring six
months or later after first-line treatment. Gemcitabine is among the
candidates as combination partner in second-line regimens. PATIENTS AND
METHODS: We performed a study with escalating doses of gemcitabine
combined with carboplatin in 26 platinum-pretreated patients with
recurrent ovarian cancer and a treatment-free interval of 6+ months.
Dose-limiting toxicity (DLT) and a maximum tolerable dose (MTD)
recommendable for further trials was evaluated. RESULTS: The DLT was
myelosuppression, mainly thrombocytopenia. No dose limiting
non-hematological toxicities were observed. The MTD of gemcitabine was
1,000 mg/m2 given on days 1 + 8 of a three-week schedule combined with
carboplatin AUC 4 given on day 1. The majority of evaluable patients
showed an objective response (62.5%), and median progression-free and
overall survival were 10 and 18+ months, respectively. CONCLUSION:
Gemcitabine-carboplatin given according to the MTD is well tolerated and
active against recurrent platinum-sensitive disease. A randomized trial
comparing carboplatin with or without gemcitabine in platinum-sensitive
ovarian cancer has already been initiated.
23
UI - 11759976
AU - Linasmita V; Wilailak S; Thakkinstian A; Srisupundit S; Tangtrakul S;
TI -
Israngura N; Bullangpoti S
Advanced epithelial ovarian carcinoma in Thai women: should we continue
to offer second-look laparotomy?
SO - J Med Assoc Thai 2001 Jul;84(7):958-65
AD - Department of Obstetrics and Gynecology, Faculty of Medicine,
Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
OBJECTIVE: To determine survival among patients with epithelial ovarian
carcinoma (EOC) who underwent a second-look laparotomy (SLL) and those
refusing the procedure. Also to analyze factor(s) influencing the
survival of the patients. METHOD AND MATERIAL: Medical records were
reviewed of patients with advanced EOC who were clinically free of
disease after primary surgery and platinum-based chemotherapy between
January 1, 1992, and December 31, 1998. All of them were offered SLL.
Measurement outcomes include patient survival and disease-free survival.
RESULTS: There were 50 patients with clinically complete remission after
chemotherapy. Sixteen patients underwent SLL, and thirty-four patients
refused the procedure (NSLL). Seven patients (43.8%) were reported to
have positive SLL. After the median follow-up time of 35 months, 12
patients had died, and 5 patients were lost to follow-up. The median
survival time for patients with SLL was about 60 months. Five-year
survival rates of patients in the SLL, and NSLL groups were 37 per cent
(95%CI = 7%-69%), and 88 per cent (95%CI = 65%-96%) respectively
(P<0.001). The median time to relapse was about 25 months for patients
with negative SLL. Five-year disease-free survival rates of patients in
the negative SLL, and NSLL groups were 28 per cent (95%CI = 4%-59%), and
54 per cent (95%CI = 34%-70%) respectively (P=0.251). By Cox regression
analysis, tumor grade was the only significant prognostic factor
influencing patients' survival (HR = 6, 95%CI of HR = 1.2-34.2).
CONCLUSION: The second-look laparotomy doesn't have a favorable impact
on overall and disease-free survival. Tumor grade is the only
independent prognostic variable for survival of the patients.
24
UI - 11780339
AU - Shen M; Feng Y; Ge B; Wu Z; Zhu M
TI -
Liposome-C-erbB2 antisense oligodoxynucleotides in human ovarian cancer
cells.
SO - Chin Med J (Engl) 2001 Jul;114(7):735-7
AD - Hospital of Obstetrics and Gynecology, Fu Dan University, Shanghai
200011, China.
OBJECTIVE: To explore the effects of liposome-C-erbB2 antisense
phosphorothioate oligodeoxynucleotides (S-ODNs) on C-erbB2
proto-oncogene expression and cell proliferation in human ovarian cancer
cells. METHODS: The effects of liposome-C-erbB2 S-ODNs on C-erbB2
protein expression, cell cycle and cell proliferation in human ovarian
cancer cells were studied by means of flow cytometry and 3H-thymidine
incorporation. RESULTS: Liposome-C-erbB2 S-ODNs can specifically reduce
C-erbB2 protein expression in human ovarian cancer cells, accompanied by
a 30% inhibition of cell proliferation. The effectiveness of
liposome-C-erbB2 S-ODNs on the expression of C-erbB2 was about 40 times
higher than that of C-erbB2 S-ODNs. CONCLUSIONS: The data suggest that
antisense therapy might be a useful method of gene therapy in ovarian
cancer. The effectiveness of C-erbB2 S-ODNs could be greatly increased
by adsorption of S-ODNs by liposomes.
25
UI - 11747321
AU - Olaitan A; Weeks J; Mocroft A; Smith J; Howe K; Murdoch J
TI -
The surgical management of women with ovarian cancer in the south west
of England.
SO - Br J Cancer 2001 Dec 14;85(12):1824-30
AD - Department of Gynaecological Oncology, St Michael's Hospital, Southwell
Street, Bristol, BS2 8EG, UK.
The surgical management of epithelial ovarian cancer in the South West
of England was studied in the two years 1997-1998 in order to determine
the factors that influence the outcome of surgery and to provide a
baseline from which to assess the effect of centralisation of cancer
services. All hospitals in the South West region of England
participating in the Regional Cancer Organisation's longitudinal study
of outcomes in gynaecological malignancies are included. Six hundred and
eighty-two patients with epithelial ovarian cancer were registered with
the RCO in the two-year study period. Five hundred and ninety-five women
were offered primary cytoreductive surgery of which 438 were said to be
optimally cytoreduced. Applying multivariate models to analyse the
outcome of surgery, older patients (OR = 0.82 per 5-year increase in
age, P = 0.0003), patients treated in hospitals managing fewer than ten
cases of ovarian cancer per year (OR = 1.92, P = 0.02) and patients with
FIGO stage 3 (OR = 0.02, P < 0.0001) or 4 (OR = 0.002, P < 0.0001)
disease were less likely to be optimally cytoreduced. Gynaecological
oncologists were 2.06 times more likely to attain optimal cytoreduction
when compared to general gynaecologists and this was statistically
significant (P = 0.01). The results from this study support the argument
that limiting surgery for ovarian malignancy to specialised surgeons
improves the extent of cytoreductive surgery.
26
UI - 11776033
AU - Sun T; Feng Y; Zhu Y; Zheng Y
TI -
Therapeutic strategy in the management of stage II-IV epithelial ovarian
carcinoma.
SO - Chin Med J (Engl) 2000 Jul;113(7):625-7
AD - Department of Obstetrics and Gynecology, Shanghai First People's
Hospital, Shanghai 200080, China.
OBJECTIVE: To investigate the optimal time of debulking in stage/II to
stage IV epithelial ovarian carcinoma, considering corresponding
patients were treated under two different regimens. Group A-76 cases (2
cases in IIa stage, 4 cases in IIb stage, 6 cases in IIc stage, 58 cases
in IIIc stage and 7 cases in IV stage) was managed according to a
traditional surgery-chemotherapy regimen; and group B-19 cases (17 cases
in IIIc stage and 2 cases in IV stage) was managed with a
chemotherapy-surgery-chemotherapy regimen. RESULTS: The optimal
debulking rate (no macroscopic residual or residual < 2 cm) in group A
was significantly lower than in group B, being 32.9% (25/76) and 68.4%
(13/19), respectively (P < 0.001). The average survival time of those
with a residual focus > 2 cm was shorter than those with a residual
focus < 2 cm, in both groups. Sixteen out of the 51 patients with a
residual focus > 2 cm had a second debulking operation, among whom 7 had
preoperative chemotherapy. All of these 7 patients had either no
residuals or residual < 2 cm. In 9 cases without preoperative
chemotherapy, the residuals were all > 2 cm. The average survival time
among these two groups were significantly different (P < 0.01).
CONCLUSION: (1) For those patients in whom optimal debulking was
clinically assessed to be possible, timely operation is mandatory. (2)
For those inoperable advanced cases, chemotherapy-surgery-chemotherapy
regimen is recommended. (3) For those with residuals > 2 cm and were
assessed to be difficult to eradicate during second-look operation,
multi-route chemotherapy (intro-arterial, intraperitoneal, and
systematic) should be given before going on the second debulking
operation. Positive attitude and proper regimen would offer better
results. (4) A multicenter prospective study would give more decisive
conclusion.
27
UI - 11677421
AU - Balbi GC; Menditto A; Calabria G; Musone R; Di Prisco L; Cassese E;
TI -
Balbi C; Cardone A
Paclitaxel and carboplatin as outpatient therapy for stage III and IV
epithelial ovarian cancer.
SO - Panminerva Med 2001 Dec;43(4):263-5
AD - Institute of Obstetrics and Gynecology, Second University of Studies of
Naples, Naples, Italy.
BACKGROUND: To determine the toxicity and the response rate of a
three-hour paclitaxel infusion and carboplatin administered as
outpatient treatment for stage III and IV epithelial ovarian cancer.
METHODS: Forty-three patients with stage III/IV epithelial ovarian
cancer underwent cytoreductive surgery and then received paclitaxel 175
mg/m2 over 3-hr infusion and carboplatin AUC5 every 21 days for six
cycles. Elegible patients had adequate bone marrow, renal and hepatic
function; G-CSF was recommended if white cell count fell under
3,000/mm3. RESULTS: No patients had hypersensivity reactions; 15 out of
43 patients (35%) required colony-stimulating factors, 39 patients (91%)
had general alopecia, three patients (7%) had severe emesis, 20 patients
(46%) had mild emesis, four patients (9%) had severe myalgias, eight
patients (18%) had moderate myalgias, one patient (2%) had grade 3
neurotoxicity. Three patients experienced grade 3 thrombocytopenia (7%).
At a median follow-up of 29 months, 32 of 43 patients are alive (74%).
Median progression-free survival is 14 months. Median overall survival
has not been reached. CONCLUSIONS: Three-hour infusion paclitaxel and
carboplatin is an effective and safe outpatient therapy for epithelial
ovarian cancer.
28
UI - 11697824
AU - Piccart MJ; Lamb H; Vermorken JB
TI -
Current and future potential roles of the platinum drugs in the
treatment of ovarian cancer.
SO - Ann Oncol 2001 Sep;12(9):1195-203
AD - Jules Bordet Institute, Chemotherapy Unit, Brussels, Belgium.
martine.piccart@bordet.be
The discovery of cisplatin more than two decades ago was the most
important therapeutic advance in the treatment of ovarian cancer. Today,
cisplatin or carboplatin in combination with paclitaxel is the most
commonly used first-line treatment for patients with advanced ovarian
cancer. Although platinum drugs remain a critical component of
chemotherapy in this type of cancer, cumulative toxicities can limit
their use. These toxicities include nephrotoxicity, neurotoxicity and
ototoxicity with cisplatin and myelosuppression with carboplatin.
Although these adverse events can often be managed, the interventions
themselves can complicate and add to the costs of treatment.
Importantly, acquired resistance to traditional platinum drugs often
develops in patients with ovarian cancer and can limit the usefulness of
these drugs. Research into new platinum drugs has focused on identifying
compounds with improved tolerability profiles and, importantly, those
which can circumvent mechanisms of platinum resistance. New platinum
drugs currently under development that are showing promise in ovarian
cancer include oxaliplatin, nedaplatin, satraplatin, BBR3464 and ZD0473.
If the encouraging in vitro activity shown by new compounds, such as
ZD0473 and BBR3464, translates into efficacy in the clinic, they may
offer an extended spectrum of activity which includes patients with
ovarian cancer resistant to the classical platinum drugs.
29
UI - 11697825
AU - Anonymous
TI -
ESMO minimum clinical recommendations for diagnosis, treatment and
follow-up of ovarian cancer.
SO - Ann Oncol 2001 Sep;12(9):1205-7
30
UI - 11783024
AU - Feng F; He X; Shi Y
TI -
[Clinical study of topotecan in the treatment of small cell lung cancer
and recurrent ovarian cancer]
SO - Zhonghua Zhong Liu Za Zhi 2001 Mar;23(2):155-8
AD - Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking
Union Medical College, Beijing 100021, China.
OBJECTIVE: To evaluate the effect and adverse reaction of China made
topotecan in the treatment of small-cell lung cancer (ACLC) and
recurrent ovarian cancer (OV). METHODS: From January to July, 2000,
topotecan was used to treat 141 patients at a dose of 1.2 mg/m2, given
daily as 30-min i.v. infusion for 5 days. Treatment was repeated once
every 3 weeks. Of the 141 patients, 118 were evaluable for therapeutic
efficacy. All the patients received a total of 286 cycles of treatment
were assessable for analysis of adverse reactions. RESULTS: Among the
evaluable patients, there were 5 CR, 35 PR, with an overall response
rate (RR) of 33.8%. There were 3 CR and 26 PR in 89 patients with SCLC
(RR 32.5%). The response rate of patients with or without prior
chemotherapy was 15.6% and 50%, respectively. In 29 patients with
recurrent OV, there were 2 CR and 9 PR (RR 37.9%). The major toxic
effect was myelosuppression. Non-hematopoietic toxicities were mild and
tolerable. CONCLUSION: Topotecan is an effective drug for the treatment
of SCLC and recurrent OV. It is still efficacious in some patients who
previously received standard chemotherapy. The major dose-limiting
toxicity is myelosuppression. The response rate and toxicity of the
domestically made topotecan are comparable with those of the imported
one.
31
UI - 11795947
AU - Woolley DE; Tetlow LC; Adlam DJ; Gearey D; Eden RD; Ward TH; Allen TD
TI -
Electrochemical monitoring of anticancer compounds on the human ovarian
carcinoma cell line A2780 and its adriamycin- and Cisplatin-resistant
variants.
SO - Exp Cell Res 2002 Feb 1;273(1):65-72
AD - University Department of Medicine, Manchester Royal Infirmary, Oxford
Road, Manchester, M13 9WL, United Kingdom.
david.woolley@mri.nwest.nhs.uk
A novel electrochemical technique which detects and monitors real-time
changes in cell behavior in vitro has been used to examine the effects
of recognized anticancer drugs on the human ovarian carcinoma cell line
A2780 and its adriamycin (A2780adr)- and cisplatin
(A2780cispt)-resistant variants. These cells, adherent to gold
electrodes or sensors, modify the extracellular microenvironment at the
cell:sensor interface, producing an electrochemical potential that is
different from that of the bulk culture medium. Confluent, adherent
A2780 cells produced an electrochemical signal, measured as an open
circuit potential (OCP), of approximately -100 mV compared to a
cell-free value of approximately -15 mV. Exposure of A2780 cells to
cisplatin (range 10(-4) to 10(-6) M), adriamycin (range 10(-5) to 10(-7)
M), and vinblastine (10(-6) M) all produced positive shifts in the OCP
signal relative to untreated control cells during 24 h of culture, but
Taxotere (range 10(-5) to 10(-7) M) had no effect. These positive shifts
in OCP signal were evident well before observations of reduced cellular
adhesion and viability after 24 h, as judged in parallel cultures with a
plastic substratum and by scanning electron microscopy. By contrast, the
same treatments applied to the A2780adr and A2780cispt variants showed
that each demonstrated different sensitivities to the same drugs applied
to the parental A2780 cells. The effects of the same four anticancer
drugs on ovarian carcinoma (A2780) and breast carcinoma (8701-BC) cell
lines showed that the former was far more responsive to adriamycin and
cisplatin. Such differences in drug sensitivities between the two cell
lines were subsequently confirmed using the conventional MTT assay over
5 days. Although this electrochemical technology readily detects changes
in cell adhesion and viability, the modified OCP signals recorded within
a few hours of anticancer drug treatments are evident well before
microscopic morphological changes become apparent. It is proposed that
these early changes in OCP signals, relative to control untreated cells,
reflect modifications of physiological/behavioral processes manifested
at the cell surface. Copyright 2001 Elsevier Science.
32
UI - 10963637
AU - Gordon AN; Granai CO; Rose PG; Hainsworth J; Lopez A; Weissman C;
TI -
Rosales R; Sharpington T
Phase II study of liposomal doxorubicin in platinum- and
paclitaxel-refractory epithelial ovarian cancer.
SO - J Clin Oncol 2000 Sep;18(17):3093-100
AD - Physicians Reliance Network, Dallas, TX, USA. alan.gordon@usoncology.com
PURPOSE: Stealth liposomal doxorubicin (Alzal Corp, Palo Alto, CA) has a
slower clearance rate than free doxorubicin, resulting in sustained
serum levels. Liposomal encapsulation also leads to increased
concentration of drug in tumor tissue. Meta-analysis of previous studies
has shown that doxorubicin has activity in epithelial ovarian cancer.
The current study was developed to examine the activity of Stealth
liposomal doxorubicin in platinum- and paclitaxel-refractory ovarian
cancer. PATIENTS AND METHODS: Patients had epithelial ovarian cancer
that either progressed on or recurred within 6 months of completion of
platinum and paclitaxel chemotherapy. All patients had measurable
disease. Stealth liposomal doxorubicin was administered at 50 mg/m(2)
every 4 weeks as a 1-hour infusion. RESULTS: Eighty-nine patients were
treated and included in an intent-to-treat analysis. There were 82
patients who were platinum and paclitaxel refractory and met all study
criteria. There was one complete response and 14 partial responses, for
a total response rate of 16.9% (95% confidence interval [CI], 9.1% to
24.6%). For platinum- and paclitaxel-refractory patients, the response
rate was 18.3% (95% CI, 9.9% to 26.7%). Median time to progression was
19. 3 weeks for the entire population. Ten patients (11.2%) withdrew
because of adverse events related to the drug (palmar-plantar
erythrodysesthesia [PPE], n = 3; asthenia, n = 2; cardiac, n = 2;
neutropenia, n = 1; stomatitis, n = 1; and edema, n = 1). There were no
drug-related fatal events. There were only eight grade 4 adverse events
attributable to the drug. Stomatitis, PPE, and skin lesions were managed
with dose reductions and delays in most cases. CONCLUSION: Stealth
liposomal doxorubicin has activity in refractory epithelial ovarian
cancer. PPE and stomatitis can usually be managed by dose adjustment.
The ease of administration makes this an attractive agent.
33
UI - 11208859
AU - Frykman G; Williams G; Pazdur R
TI -
Conflicting phase II efficacy data for Doxil.
SO - J Clin Oncol 2001 Jan 15;19(2):596-7
34
UI - 11695811
AU - Recchi F; De Filippis S; Rosselli M; Saggio G; Carta G; Rea S
TI -
Primary chemotherapy in stage IV ovarian cancer. A prospective phase II
study.
SO - Eur J Gynaecol Oncol 2001;22(4):287-91
AD - Oncologic Unit, Avezzano, Italy.
BACKGROUND AND RATIONALE: Non-curative surgical cytoreduction of
advanced tumors is associated with increased proliferation of the
remaining tumor cells. Thus, appropriate preoperative chemotherapy
should prevent both cell proliferation and the increase of resistant
cells. The aim of the present study was to evaluate the efficacy and
toxicity of primary chemotherapy (P-CT) in previously untreated patients
with stage IV ovarian cancer (OC). PATIENTS AND METHODS: Thirty-four
with P-CT. Eligibility criteria included: histologically or
cytologically confirmed, unresectable stage IV OC and performance status
< or = 3. P-CT consisted of four courses of carboplatin,
carboplatin thereafter. Surgery followed P-CT. After the operation
patients received two further courses of chemotherapy that were tailored
according to their individual response. Median (M) age was 61 years,
range 32-73; median performance status was 2. A total number of 197
courses of CT were administered, median 5.7 per patient. RESULTS:
Complete or partial response (CR, PR) was observed in 28 patients
(response rate 82%, 95% CI: 65.4% to 93.2%), disease stability and
progression (SD, PD) was observed in three and three patients,
respectively. Median time to progression was 16.45 months (range
4.8-90.4+), median survival time was 28 months (range 4.5 - 90.4+):
1-year survival rate was 94%. Toxicity according to WHO: nausea and
vomiting grade (G) 2, 30% of patients; gastrointestinal G 2-3, 20% of
patients; alopecia G 3, 88% of patients; hematological G 3-4, 73% of
patients; neurologic G 2, 12% of patients. Nine pathological CRs were
observed. CONCLUSION: Neoadjuvant treatment with CBDCA with either CTX
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