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NCI CANCERLIT® Search: Therapy of Ovarian Cancer - May 2002
National Cancer Institute®
Last Modified: May 1, 2002
Table of Contents
1
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.
2
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).
3
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.
bent@neuh.azr.nl
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.
4
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
5
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.
jens.huober@med.uni-tuebingen.de
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.
6
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.
7
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. alan.gordon@usoncology.com
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.
8
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.
9
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.
10
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. al.covens@tsrcc.on.ca
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.
11
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. stan.kaye@rmh.nthames.nhs.uk
12
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.
13
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.
14
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.
paparahman@hotmail.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.
15
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.
16
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
17
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. j.hernando@uni-bonn.de
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.
18
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.
19
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.
20
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.
21
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.
22
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.
23
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.
24
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.
markmam@ccf.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.
25
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. janni@fk-i.med.uni-muenchen.de
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.
26
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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