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NCI CANCERLIT® Search: Therapy of Ovarian Cancer - March 2002
National Cancer Institute®
Last Modified: March 1, 2002
Table of Contents
1
UI - 10995813
AU - Vergote I; Rustin GJ; Eisenhauer EA; Kristensen GB; Pujade-Lauraine E;
TI -
Parmar MK; Friedlander M; Jakobsen A; Vermorken JB
Re: new guidelines to evaluate the response to treatment in solid tumors
[ovarian cancer]. Gynecologic Cancer Intergroup.
SO - J Natl Cancer Inst 2000 Sep 20;92(18):1534-5
2
UI - 11778075
AU - Pierelli L; Perillo A; Ferrandina G; Salerno G; Rutella S; Fattorossi A;
TI -
Battaglia A; Rughetti A; Nuti M; Cortesi E; Leone G; Mancuso S; Scambia
G
The role of growth factor administration and T-cell recovery after
peripheral blood progenitor cell transplantation in the treatment of
solid tumors: results from a randomized comparison of G-CSF and GM-CSF.
SO - Transfusion 2001 Dec;41(12):1577-85
AD - Hematology and Hemotransfusion Service, Institute of Obstetrics and
Gynecology, Sacred Heart Catholic University, Rome, Italy.
luca@pierelli.it
BACKGROUND: Peripheral blood progenitor cell (PBPC) transplantation
(PBPCT) combined with post-PBPCT administration of myelopoietic growth
factors is a valid therapeutic intervention to rapidly restore
hematopoiesis after the delivery of intensive, myeloablative cancer
chemotherapy. On the other hand, the best growth factor regimen to
potentiate PBPC-mediated immunohematopoietic recovery has yet to be
determined. STUDY DESIGN AND METHODS: In a randomized evaluation, the
effects produced by post-PBPCT G-CSF and GM-CSF on myeloid/lymphoid
recovery and transplant outcome in women with chemosensitive cancer were
compared. Thirty-seven ovarian cancer patients and 34 breast cancer
patients ranging in age from 24 to 60 years were treated with
carboplatin, etoposide, and melphalan (CEM) high-dose chemotherapy and
then randomly assigned to receive G-CSF (5 microg/kg subcutaneously) or
GM-CSF (5 microg/kg subcutaneously) until Day 13 after PBPCT. Patients
were compared in regard to hematopoietic recovery, posttransplant
clinical management, and immune recovery. Finally, clinical outcome was
estimated as time to progression and overall survival. RESULTS:
Hematopoietic recovery and posttransplant clinical management were
comparable in both the G-CSF and GM-CSF series. Conversely,
significantly higher T-cell counts were observed in G-CSF-treated
patients during the early and late posttransplant follow-up. Patients
who received G-CSF showed a significantly longer median time to
progression. A parallel analysis revealed that patients in whom a higher
CD3+ count was recovered had a significantly longer overall survival and
time to progression. CONCLUSION: The enhancement of post-PBPCT T-cell
recovery observed in G-CSF-treated patients encourages the use of G-CSF
to ameliorate immune recovery, which seems to play a role in post-PBPCT
control of disease in cancer patients. GM-CSF might be administered to
prolong immunosuppression after autologous PBPCT for autoimmune diseases
or allogeneic PBPCT.
3
UI - 11865633
AU - Furue H; Ikeda M; Tsukagoshi S; Taguchi T; Fujii T; Rikimaru T
TI -
[Clinical usefulness of ondansetron injection in patients receiving
cancer chemotherapy]
SO - Gan To Kagaku Ryoho 2002 Feb;29(2):261-71
AD - Teikyo University.
Before and after launch of 5-HT3, antagonist, necessary dose and
duration of chemotherapy were compared between the patients who were
confirmed to have undergone chemotherapy before the launch of 5-HT3
antagonist (retrospective group) and the ones currently using
ondansetron (OND) for chemotherapy-induced emesis (prospective group).
Clinical usefulness of OND was evaluated through survey on quality of
life (QOL) to patients and questionnaires to physicians, nurses &
patients. Necessary dose of chemotherapy was evaluated by investigating
actual dose of cisplatin (CDDP). As the result, necessary dose of CDDP
was confirmed to be different between retrospective and prospective
groups. The influence on the actual CDDP dose was observed with or
without use of G-CSF or by recommended dose of CDDP, while no influence
by 5-HT3 antagonist was observed. For necessary duration of
chemotherapy, significant difference was not observed between
retrospective or prospective groups. On the other hand, actual CDDP dose
or necessary duration of chemotherapy were confirmed to be greatly
affected by chemotherapy-induced adverse events such as blood disorder
(e.g. bone marrow suppression) or renal disorder, rather than
chemotherapy-induced emesis. As the result of QOL survey to patients and
other questionnaires to medical staff & patients, the fact of
chemotherapy-induced emesis to lower the patient's QOL as well as the
importance of emetic control was confirmed. It was also confirmed that
the workload of nurses or other medical staff has lessened since the
launch of 5-HT3 antagonists.
4
UI - 11750848
AU - Vignati S; Codegoni A; Polato F; Broggini M
TI -
Trail activity in human ovarian cancer cells: potentiation of the action
of cytotoxic drugs.
SO - Eur J Cancer 2002 Jan;38(1):177-83
AD - Laboratory of Molecular Pharmacology, Department of Oncology, Istituto
di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milan,
Italy.
The ability of the TRAIL ligand to induce cell killing in three ovarian
cancer cell lines was investigated using a glutathione-S-transferase
(GST)-TRAIL fusion protein. One of the three lines was sensitive to
TRAIL, which induced cell killing in a range of concentrations similar
to those necessary to kill the TRAIL-sensitive leukaemic cell line
Jurkat. The relative mRNA expression of the four TRAIL receptors did not
explain the different sensitivities of the three ovarian cancer cell
lines to TRAIL treatment. The TRAIL-sensitive IGROV-1 cell line
expressed slightly lower levels of the anti-apoptotic protein FLIP than
the two TRAIL-insensitive cell lines (A2780 and SKOV-3). Nevertheless,
although TRAIL did not significantly reduce cell growth in the A2780 and
SKOV-3 cells it did enhance the activity of paclitaxel and cisplatin
(DDP), the two most widely used drugs for the treatment of ovarian
cancer, increasing their ability to induce apoptosis. The use of TRAIL
in combination with classical anticancer agents might thus boost the
apoptotic response, improving the activity of DDP and paclitaxel in
ovarian cancer.
5
UI - 11823695
AU - Plaxe SC; Blessing JA; Morgan MA; Carlson J; Gynecologic Oncology Group
TI -
Phase II trial of pyrazoloacridine in recurrent platinum-resistant
ovarian cancer: a Gynecologic Oncology Group study.
SO - Am J Clin Oncol 2002 Feb;25(1):45-7
AD - Department of Reproductive Medicine, Division of Gynecologic Oncology,
University of California-San Diego Medical Center, 402 Dickinson Street,
San Diego, CA 92103-8433, U.S.A.
The Gynecologic Oncology Group performed a Phase II study to determine
the response rate of pyrazoloacridine (PZA) in patients with
platinum-resistant ovarian cancer. PZA was administered at a dose of 750
mg/m2 intravenously over 3 hours every 3 weeks. Among 24 evaluable
patients, there was 1 (4.2%) complete and 1 (4.2%) partial response. The
major toxicities were hematologic. With the dose and schedule used, PZA
had only modest activity in this population.
6
UI - 11857006
AU - van der Burg ME; de Wit R; van Putten WL; Logmans A; Kruit WH; Stoter G;
TI -
Verweij J
Weekly cisplatin and daily oral etoposide is highly effective in
platinum pretreated ovarian cancer.
SO - Br J Cancer 2002 Jan 7;86(1):19-25
AD - Department of Medical Oncology, Rotterdam Cancer Institute and
University Hospital, Rotterdam, P.O. Box 5201, 3008 AE Rotterdam, The
Netherlands.
We investigated the potential of weekly cisplatin and daily oral
etoposide followed by oral etoposide maintenance therapy in patients
with platinum-refractory ovarium cancer. One hundred and seven patients
were entered on the study, 98 patients completed the induction therapy
consisting of cisplatin at either 50 or 70 mg m(-2) weekly for six
administrations plus oral etoposide at a dose of 50 mg daily. Of these
98 patients, 38 had a platinum treatment-free interval of more than 12
months, 32 had an interval between 4 and 12 months, and 28 had
progressed during or within 4 months after last platinum therapy. We
assessed response rates and time to progression, and also response
duration and survival. Analyses were done on the 98 evaluable patients.
All 107 patients were considered evaluable for toxicity. Of the 38
patients with a treatment-free interval of more than 12 months, 92%
responded, with 63% complete responses. The median progression-free
survival in these patients was 14 months, and the median survival was 26
months. Of the 32 patients with an interval of 4-12 months, 91%
responded, with 31% complete responses, a median progression-free
interval of 8 and a median overall survival of 16 months. Of the 28
patients with platinum-refractory disease, 46% as yet responded, with
29% complete responses, median progression-free interval of 5 and an
overall survival of 13 months. Haematologic and non-haematologic,
particularly renal toxicity and neurotoxicity, were notably mild. We
conclude that this intensive regimen of weekly cisplatin plus daily
etoposide is highly effective and well tolerated in patients with
ovarian cancer relapsing after conventional platinum-based combination
chemotherapy, including patients who have progressed during or within 4
months after platinum treatment.
7
UI - 11857002
AU - Clamp A; Jayson GC
TI -
Weekly platinum chemotherapy for recurrent ovarian cancer.
SO - Br J Cancer 2002 Jan 7;86(1):2-4
8
UI - 11683313
AU - Fitch MI; Gray RE; Franssen E
TI -
Perspectives on living with ovarian cancer: older women's views.
SO - Oncol Nurs Forum 2001 Oct;28(9):1433-42
AD - Toronto-Sunnybrook Regional Cancer Centre, Ontario, Canada.
marg.fitch@tsrcc.on.ca
PURPOSE/OBJECTIVES: To describe the perspectives of older women
regarding their experiences living with ovarian cancer. DESIGN:
Retrospective survey. SETTING: Canada. SAMPLE: 146 women, 61 years of
age or older, diagnosed with ovarian cancer. METHODS: Questionnaire
distributed by oncologists and nurses in 26 cancer clinics across Canada
to eligible patients during a six-week period. MAIN RESEARCH VARIABLES:
Patient problems experienced, help received for problems, impact of
illness, quality of life, importance of and satisfaction with
information received, and helpfulness of others. FINDINGS: Women
experienced, on average, 5.2 problems since diagnosis. The most
frequently identified problems were side effects (54%), fear of
recurrence (45%), bowel difficulties (43%), and difficulty sleeping
(36%). Of the women who experienced problems, the proportion who felt
they received adequate help ranged from 36%-74%. Approximately half
(57%) of these women reported a lifestyle change. A significant
difference was observed in quality of life before and after the
diagnosis of ovarian cancer (p = 0.0002). When asked about the desire to
talk about their difficulties with cancer, only 54% indicated that they
wanted to talk. Approximately one-quarter of the women were satisfied
with the information they received regarding complementary (25%) and
alternative (23%) therapies, and how to speak with other women living
with ovarian cancer (28%). Thirty-five percent were satisfied with the
information they received about self-help groups. CONCLUSION: Ovarian
cancer has a significant impact on older women, and many perceive they
are not receiving adequate assistance for problems they experience.
IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses should conduct
comprehensive assessments of the needs of older women with ovarian
cancer, refer those who require specialized counseling, and provide
information desired by patients with ovarian cancer about available
resources.
9
UI - 11750835
AU - Sparreboom A; de Jonge MJ; Verweij J
TI -
The use of oral cytotoxic and cytostatic drugs in cancer treatment.
SO - Eur J Cancer 2002 Jan;38(1):18-22
AD - Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den
Hoed Kliniek) and University Hospital Rotterdam, 3075 EA Rotterdam, The
Netherlands. sparreboom@onch.azr.nl
Although with a few exceptions, most new anticancer agents are initially
developed for intravenous use, oral treatment with anticancer agents is,
if feasible, to be preferred, as this route of administration is
convenient to patients, reduces administration costs and facilitates the
use of more chronic treatment regimens. Recent studies have identified
various physiological barriers limiting the oral absorption of
anticancer drugs. Presently, several strategies are explored to alter
the low and variable oral bioavailability of several important
anticancer agents by taking advantage of an intentional interaction
between anticancer agents and drugs that modulate active intestinal drug
transporters or (intestinal) enzymes.
10
UI - 11750840
AU - Gore M; Oza A; Rustin G; Malfetano J; Calvert H; Clarke-Pearson D;
TI -
Carmichael J; Ross G; Beckman RA; Fields SZ
A randomised trial of oral versus intravenous topotecan in patients with
relapsed epithelial ovarian cancer.
SO - Eur J Cancer 2002 Jan;38(1):57-63
AD - Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.
martin.gore@rmh.nthames.nhs.uk
A multicentre, randomised study was carried out in Europe, South Africa
and North America to compare the activity and tolerability of oral
versus intravenous (i.v.) topotecan in patients with relapsed epithelial
ovarian cancer. Patients who had failed first-line therapy after one
platinum-based regimen, which could have included a taxane, were
randomised to treatment with either oral (p.o.) topotecan, 2.3
mg/m(2)/day or i.v. topotecan 1.5 mg/m(2)/day for 5 days every 21 days.
Patients were stratified by prior paclitaxel exposure, interval from
previous platinum therapy and tumour diameter. 266 patients were
randomised. Response rates were 13% orally (p.o.) and 20% (i.v.) with a
complete response in 2 and 4 patients, respectively. The difference in
the response rates was not statistically significant. Median survival
was 51 weeks (p.o.) and 58 weeks (i.v.) with a risk ratio of death (p.o.
to i.v. treatment) of 1.361 (95% confidence interval (CI): 1.001,
1.850). Median time to progression was 13 weeks (p.o.) and 17 weeks
(i.v.). The principal toxicity was myelosuppression although grade 3/4
neutropenia occurred less frequently in those receiving oral topotecan.
Toxicity was non-cumulative and infectious complications were relatively
infrequent. Non-haematological toxicity was generally mild or moderate.
The incidence of grade 3/4 gastrointestinal events was slightly higher
for oral than i.v. topotecan. Oral topotecan shows activity in
second-line ovarian cancer and neutropenia may be less frequent than
with the i.v. formulation. A small, but statistically significant,
difference in survival favoured the i.v. formulation, but the clinical
significance of this needs to be interpreted in the context of
second-line palliative treatment. Oral topotecan is convenient and well
tolerated and further studies to clarify its role are ongoing.
11
UI - 11812075
AU - Perez-Gracia JL; Carrasco EM
TI -
Tamoxifen therapy for ovarian cancer in the adjuvant and advanced
settings: systematic review of the literature and implications for
future research.
SO - Gynecol Oncol 2002 Feb;84(2):201-9
AD - Clinical Research Department, Eli Lilly and Company, Alcobendas, Madrid,
Spain. jlgracia@lilly.com
BACKGROUND: Ovarian neoplasms frequently express hormonal receptors and
are sensitive to hormonal manipulations, as shown by preclinical and
clinical studies. However, despite the outstanding relevance of hormonal
adjuvant therapy in breast cancer and the importance of receptor status
as a predictive factor, few trials have addressed these issues in
ovarian cancer. METHODS: Computerized and manual searches were performed
to identify preclinical and clinical studies evaluating single-agent
tamoxifen activity in ovarian cancer or any kind of hormonal therapy
employed as adjuvant therapy for ovarian cancer. RESULTS: In advanced
tumors, none of the trials was performed exclusively in chemonaive
patients, but those including less heavily pretreated patients showed
greater response rates. Some studies found a correlation between
receptor status and activity (although differences were not
significant), whereas other trials did not. Nevertheless, none were
specifically designed to answer this question. Few randomized trials
comparing hormonal treatment and chemotherapy versus chemotherapy alone
were identified. Although their results were negative, all were small,
and none was designed with the rigor that allowed adjuvant hormonal
therapy to become successfully established in breast cancer. CONCLUSION:
The activity of tamoxifen in advanced ovarian cancer has not been
adequately evaluated and its role may have been underestimated.
Furthermore, the relevance of adjuvant hormonal therapy in ovarian
cancer and the predictive value of hormonal receptors have never been
studied in well-designed trials. Additional studies to clarify the role
of tamoxifen for this indication are warranted. B)2001 Elsevier Science.
12
UI - 11812079
AU - Bao R; Selvakumaran M; Hamilton TC
TI -
Targeted gene therapy of ovarian cancer using an ovarian-specific
promoter.
SO - Gynecol Oncol 2002 Feb;84(2):228-34
AD - Ovarian Cancer Program, Fox Chase Cancer Center, Philadelphia,
Pennsylvania 19111, USA.
OBJECTIVES: The "suicide" gene therapy of cancer using promoters such as
cytomegalovirus could cause severe toxicity to normal tissues due to a
lack of specificity of prodrug activation. Therefore, we investigated
gene therapy of ovarian cancer using ovarian-specific promoter (OSP1) to
limit the synthesis of the prodrug activating enzyme HSVtk to ovarian
cancer cells. METHODS: The HSVtk expressing plasmid pOSP1-HSVtk was
created and transfected into an ovarian cancer cell line OVCAR3. The
ganciclovir (GCV) sensitivity of the stable transfectants was evaluated
with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
method. Tissue specificity of this promoter was evaluated by comparing
the sensitivity to GCV between ovarian and nonovarian cancer cell lines
after they were transfected with pOSP1-HSVtk. One transfectant sensitive
to GCV was implanted intraperitoneally to immunocompromised mice which
were treated subsequently with GCV. Furthermore, this ovarian cancer
survival model was used to evaluate the in vivo efficacy of cationic
lipid mediated pOSP1-HSVtk gene delivery followed by GCV treatment.
RESULTS: Stable transfectants of OVCAR3 cells bearing OSP1-HSVtk became
more sensitive to GCV treatment compared to the parental cell line and
vector transfected OVCAR3 cell line. OSP1-HSVtk could specifically
sensitize the OVCAR3 ovarian cancer cell line to GCV. SCID mice
transplanted with the OVCAR3 transfectant and treated with GCV survived
longer than the mice without GCV treatment (P = 0.032). In vivo gene
delivery mediated by a cationic lipid (GL67) followed by GCV treatment
yielded a longer survival in the OVCAR3 survival model (P = 0.016).
CONCLUSIONS: The OSP1 promoter can selectively direct suicide gene
therapy of ovarian cancer and the in vivo efficacy is improved by using
a cationic lipid GL67 as delivery vehicle as opposed to the direct
injection of plasmid. B)2001 Elsevier Science.
13
UI - 11848519
AU - Gadducci A; Cosio S; Cionini L; Genazzani AR
TI -
Neoadjuvant chemotherapy and concurrent chemoradiation in the treatment
of advanced cervical cancer.
SO - Anticancer Res 2001 Sep-Oct;21(5):3525-33
AD - Department of Procreative Medicine, University of Pisa, Italy.
a.gadducci@obgyn.med.unipi.it
The role of chemotherapy in the management of advanced cervical cancer
has been long debated. Whereas some phase II trials have shown promising
results with neoadjuvant chemotherapy followed by irradiation, most
phase III trials failed to demonstrate any benefit with this sequential
treatment in terms of loco-regional control and survival, mainly because
chemotherapy could cause accelerated tumor clonogen resistant cell
repopulation The data on cisplatin-based neoadjuvant chemotherapy before
surgery appear to be more promising. This treatment modality can
increase the operability rate and reduce the incidence of positive nodes
and other pathological risk factors. However, very few randomized trials
comparing cisplatin-based neoadjuvant chemotherapy followed by radical
hysterectomy versus conventional irradiation treatment are currently
available, whilst data about long-term survival of
chemo-surgical-treated patients are scanty. Recently five prospective
randomized trials compared concurrent cisplatin-based chemotherapy and
irradiation versus hydroxyurea plus irradiation or irradiation alone.
All showed a significant improvement in the outcome of patients treated
with concurrent cisplatin-based chemoradiation. Based on these data, the
National Cancer Institute released a Clinical Announcement stating that
concurrent cisplatin-based chemoradiation should be the new standard of
therapy for high-risk early stage and locally advanced cervical cancer.
The introduction of taxanes in both neoadjuvant chemotherapy followed by
radical hysterectomy and concurrent chemoradiation could further improve
the results of these two treatment modalities. A multicenter randomized
trial comparing chemo-surgical treatment with concurrent chemoradiation
is warranted to better define the optimum therapeutic strategy for
patients with advanced cervical cancer.
14
UI - 11848522
AU - Mobus V; Pfaff PN; Volm T; Kreienberg R; Kaubitzsch S
TI -
Long time therapy with topotecan in patients with recurrence of ovarian
carcinoma.
SO - Anticancer Res 2001 Sep-Oct;21(5):3551-6
AD - Department of Obstetrics and Gynecology, Stadtische Kliniken, Frankfurt,
Germany. MoebusVolk@aol.com
BACKGROUND: In several phase II and III topotecan studies the large
number of patients with stable disease is striking. Since no severe
organ toxicity has been described for topotecan, long-term therapy with
topotecan seems to be reasonable. In this summary we present evidence,
that long-term topotecan therapy can be managed without cumulative
hematological and non-hematological toxicity. PATIENTS AND METHODS:
Thirty-three patients with recurrent ovarian cancer, who were treated
with at least 7 courses of topotecan, were evaluated in this
retrospective study (patient database from SmithKline Beecham, Germany).
Most of the patients had more than 2 previous courses of chemotherapy.
The starting dose was between 1.0 and 1.5 mg/m2 topotecan administered
for 5 days every 3 weeks as an i.v. infusion. All patients were
evaluated for toxicity, 32 patients for response. RESULTS: The 33
patients received 343 courses of topotecan, an average of more than 10
courses per patient. The highest number of courses given to a single
patient was 33. The hematotoxicity was in the expected range, but
toxicity was not cumulative. The number of interventions for growth
factors and blood cell transfusions were constant over the whole
therapy. Dose reductions were conducted in more than 75% of the patients
as early as in course two. There was no grade 3 or 4 non-hematological
toxicity. Alopecia was the only toxicity to be cumulative. Remissions
were observed in 12 out of 32 eligible patients. The remissions were
achieved after an average of 4.3 courses (range 2-7). The median time to
progression was 33 weeks. CONCLUSION: Long-term therapy with topotecan
is reasonable and can be conducted without cumulative hematological
toxicity.
15
UI - 11848523
AU - Gadducci A; Conte P; Cianci C; Negri S; Genazzani AR
TI -
Treatment options in patients with recurrent ovarian cancer.
SO - Anticancer Res 2001 Sep-Oct;21(5):3557-64
AD - Department of Procreative Medicine, Pisa, Italy.
a.gadducci@obgyn.med.unipi.it
The majority of patients with advanced ovarian cancer need a second-line
treatment for recurrent disease after surgical cytoreduction and
first-line chemotherapy. In these patients, treatment planning is mainly
dependent on the platinum-free-interval. The patients may be
distinguished as platinum-refractory (progression under platinum-based
therapy), platinum-resistant (relapse within 6 months), or
platinum-sensitive (relapse after 6 months). Patients with
platinum-refractory or -resistant disease should be encouraged to enter
clinical trials. Alternatively, these patients could receive tamoxifen
or a non-platinum single-agent therapy. Since response rate and duration
to different single-agents are similar, patient convenience, toxicities
from prior treatment, side-effects and costs play a role in the drug
selection for salvage chemotherapy. Patients with platinum-sensitive
disease should receive carboplatin based or carboplatin-plus
paclitaxel-based regimens. Secondary surgical cytoreduction may have a
role in highly selected patients with good performance status, with long
disease-free interval and without extra-abdominal or liver metastases.
16
UI - 11848547
AU - Peters-Engl C; Medl M; Denison U; Sevelda P; Leodolter S; Petru E
TI -
Does long-term application of granulocyte colony-stimulating factor
adversely influence overall survival in patients with ovarian cancer? A
clinical study.
SO - Anticancer Res 2001 Sep-Oct;21(5):3701-6
AD - Department of Gynecology and Obstetrics, Lainz Medical Center, Vienna,
Austria.
The purpose of this study was to investigate the effect of long-term
administration of G-CSF with regard to its impact on overall survival of
patients with ovarian cancer. We report the results of a non-randomized
trial on 64 patients with advanced ovarian cancer treated with 6 cycles
of conventional chemotherapy. Chemotherapy comprised carboplatin 400
mg/m2 and epirubicin 70 mg/m2 on day 1 of each cycle and prednimustine
100 mg/m2 on days 3 to 7, every 28 days. Thirty-three patients received
CEP chemotherapy with G-CSF support whereas 31 women received CEP
chemotherapy alone. The schedule of G-CSF was 5 mg/kg/day subcutanously
on days 8 to 21 of each cycle. The severity of reduction in white cells
and neutrophil count was significantly different in the two treatment
groups (p<0.05), with more toxicity in the non- G-CSF group. G-CSF users
had a non significant 0.88-fold lower risk of dying from ovarian cancer
(95% CI, 0.48-1.60, p=0.678). In a survival analysis using a Cox
proportional hazards model, residual tumor remained as an independent
prognostic factor. The increasing amount of residual tumor resulted in a
1.767-fold higher risk (95% CI, 1.23-2.53, p=0.002) of death secondary
to the underlying disease. In conclusion, this trial has failed to
demonstrate any negative impact on patients' overall survival for the
additional use of G-CSF with platinum-based chemotherapy; our results
were consistent with the beneficial effects of G-CSF treatment on
cytotoxic chemotherapy-induced myelosuppression.
17
UI - 11603001
AU - Meredith RF; Alvarez RD; Partridge EE; Khazaeli MB; Lin CY; Macey DJ;
TI -
Austin JM Jr; Kilgore LC; Grizzle WE; Schlom J; LoBuglio AF
Intraperitoneal radioimmunochemotherapy of ovarian cancer: a phase I
study.
SO - Cancer Biother Radiopharm 2001 Aug;16(4):305-15
AD - Department of Radiation Oncology, University of Alabama at Birmingham,
Comprehensive Cancer Center, Wallace Tumor Institute-117, 1530 3rd
Avenue South, Birmingham, AL 35294-6832, USA. rmeredith@uabmc.edu
A phase I trial was designed to examine the feasibility of combining
interferon and Taxol with intraperitoneal radioimmunotherapy
(177Lu-CC49). Patients with recurrent or persistent ovarian cancer
confined to the abdominal cavity after first line therapy, Karnofsky
performance status > 60, adequate liver, renal and hematologic function,
and tumor that reacted with CC49 antibody were enrolled. Human
recombinant alpha interferon (IFN) was administered as 4 subcutaneous
injections of 3 x 10(6) U on alternate days beginning 5 days before RIT
to increase the expression of the tumor-associated antigen, TAG-72. The
addition of IFN increased hematologic toxicity such that the maximum
tolerated dose (MTD) of the combination was 40 mCi/m2 compared to
177Lu-CC49 alone (45 mCi/m2). Taxol, which has radiosensitizing effects
as well as antitumor activity against ovarian cancer, was given
intraperitoneally (i.p.) 48 hrs before RIT. It was initiated at 25 mg/m2
and escalated at 25 mg/m2 increments to 100 mg/m2. Subsequent groups of
patients were treated with IFN + 100 mg/m2 Taxol + escalating doses of
177Lu-CC49. Three or more patients were treated in each dose group and
34 patients were treated with the 3-agent combination. Therapy was well
tolerated with the expected reversible hematologic toxicity. The MTD for
177Lu-CC49 was 40 mCi/m2 when given with IFN + 100 mg/m2 Taxol.
Interferon increased the effective whole body half-time of radioactivity
and the whole body radiation dose. Taxol did not have a significant
effect on pharmacokinetic or dosimetry parameters. Four of 17 patients
with CT measurable disease had a partial response (PR) and 4 of 27
patients with non-measurable disease have progression-free intervals of
18+, 21+, 21+, and 37+ months. The combination of intraperitoneal Taxol
chemotherapy (100 mg/m2) with RIT using 177Lu-CC49 and interferon was
well tolerated, with bone marrow suppression as the dose-limiting
toxicity.
18
UI - 11772280
AU - Harries M; Kaye SB
TI -
Recent advances in the treatment of epithelial ovarian cancer.
SO - Expert Opin Investig Drugs 2001 Sep;10(9):1715-24
AD - CRC Department of Medical Oncology, The Royal Marsden Hospital, Downs
Road, Sutton, Surrey, SM2 5PT, UK. mark.harries@rmh.nthames.nhs.uk
Ovarian cancer leads to more fatalities than any other form of
gynaecological cancer in North America and Europe. Over the last 30
years survival figures have improved somewhat due to improvements in
diagnosis, surgery and chemotherapy. Despite these advances, the
majority of patients will die from their disease, with the overall
5-year survival being just 30%. The majority of patients with this
disease will require treatment with cytotoxic chemotherapy. It is now
well established that the platinum agents (cisplatin or carboplatin) are
the most important drugs to be included in first-line regimens. More
recently, randomised trials have confirmed the benefit of the addition
of taxanes to platinum-containing regimens and the standard of care has
become the combination of carboplatin and paclitaxel. Several unanswered
questions remain regarding the optimal schedule, the optimum duration of
treatment, possible benefits to be gained from the addition of other
drugs and whether paclitaxel the best taxane. Despite high response
rates to first line chemotherapy, the majority of patients with advanced
ovarian cancer will relapse and will be candidates for further
chemotherapy, which can palliate symptoms and improve survival even in
recurrent disease. For a patient relapsing within six months of
first-line treatment, studies have shown that there is little point in
rechallenge with the same drugs. However, for patients who have a longer
treatment-free interval the response rates to rechallenge with platinum
is significant. A number of drugs have been shown to have activity in
platinum- and taxane-refractory disease and are approved for this and/or
other applications. These include topotecan, etoposide, pegylated
liposomal doxorubicin, epirubicin, gemcitabine, altretamine, oxaliplatin
and vinorelbine. Anti-oestrogens such as tamoxifen have a small but
significant response rate. Recurrent ovarian cancer is a good setting to
test investigational agents and compounds with promising activity
including new platinums and taxoids, as well as a range of new
compounds. Non-cytotoxic approaches that are showing promise include
therapies designed to overcome drug resistance, signal transduction
inhibitors, immunotherapy and gene therapy.
19
UI - 11857347
AU - Vikhanskaya F; Falugi C; Valente P; Russo P
TI -
Human papillomavirus type 16 E6-enhanced susceptibility to apoptosis
induced by TNF in A2780 human ovarian cancer cell line.
SO - Int J Cancer 2002 Feb 20;97(6):732-9
AD - Molecular Pathology Section, Laboratory of Experimental Oncology,
National Institute for Research on Cancer, Genoa, Italy.
In our study, we show that expression of HPV-16 E6 sensitizes
TNF-induced cytotoxicity of human ovarian cancer cell line A2780. This
effect is not related to a different number of TNF receptors present on
cell membrane. The major induction of massive apoptosis induced by TNF
is not p53- and p21(waf-1)-dependent but it is principally related to
NF-kappaB inhibition in A2780/E6 cells. Consistently to NF-kappaB
inhibition a rapidly release of cytochrome c and severe induction of DNA
fragmentation are seen in A2780/E6 cells. Also in human colon cancer
cell line HCT-116/E6 the expression of HPV-16 E6 enhances
TNF-cytotoxicity. This effect is not present in the HCT-116/mu-p53 clone
(transfected with a dominant-negative mutated p53 transgene). Thus,
taken together all these observations suggest that HPV-16 E6 sensitizes
A2780 and HCT-116 cells to TNF; this effect is not p53-dependent, but it
is essentially mediated through an inhibition in activating NF-kappaB
activities. Copyright 2001 Wiley-Liss, Inc.
20
UI - 11760646
AU - Lehoczky O; Bagameri A; Udvary J; Pulay T
TI -
[Second-line chemotherapy with paclitaxel for ovarian cancer]
SO - Orv Hetil 2001 Oct 21;142(42):2299-301
AD - Nogyogyaszati Onkologiai Osztaly, Orszagos Onkologiai Intezet, Budapest.
loczky@oncol.hu
The authors summerize the results of second-line combination
chemotherapy with paclitaxel (175 mg/m2, 3h) and carboplatin (AUC 5
mg/ml.min) in patients with recurrent epithelial ovarian cancer. The
paclitaxel/carboplatin therapy was applied in 57 patients in 297 courses
(median course/patient was 5, range 2, 12). Complete response (CR) was
found in 3 patients (3/57 = 5%), however the tumorous process progressed
after some time. The median progression free interval (PFI) was found to
be 15 (range 3,130) weeks, with an average of 24.3 +/- 26.5 weeks. The
authors conclude, that second-line paclitaxel combination therapy
produces poorer results than the first-line treatment. These results,
which are similar to the literature data have led to the agreement:
paclitaxel can be applied in ovarian cancer patients only in first-line
chemotherapy in Hungary from the year 2000.
21
UI - 11844842
AU - Abramson N; Stokes PK; Luke M; Marks AR; Harris JM
TI -
Ovarian and papillary-serous peritoneal carcinoma: pilot study with
thalidomide.
SO - J Clin Oncol 2002 Feb 15;20(4):1147-9
22
UI - 11847508
AU - Takeuchi T; Suzuki h h; Hayashi u u; Shinagawa T; Araki T
TI -
Primary ovarian tumor undergoing surgical management during pregnancy.
SO - J Nippon Med Sch 2002 Feb;69(1):39-42
AD - Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo,
Japan.
The aim of this study was to evaluate the preoperative symptoms of
patients with primary ovarian tumors undergoing surgery during pregnancy
and non-pregnancy. We retrospectively analyzed the medical records of 71
pregnant patients who underwent surgery for primary ovarian tumors
(pregnant) and 580 non-pregnant patients (non-pregnant) aged 15similar44
years old. In the non-pregnant group, 79.7% of the patients complained
of abdominal pain at the first examination. However, in the pregnant
group, 62.0% of the patients reported no symptoms and 31.0% of them
reported abdominal pain (p<0.05). There were no significant differences
in the percentage of ovarian malignancies between the two groups (8.5%
vs. 6.6%). However, the incidence of the advanced stage of
greater-than-or-equal Ic in ovarian malignancies in the non-pregnant
group was 42.1%, while it was 0% (p<0.05) in the pregnant group. Ovarian
tumors including ovarian malignancies were significantly more frequently
diagnosed with no symptoms in the pregnant group than in the
non-pregnant group.
23
UI - 11855871
AU - Gonzalez-Martin A; Crespo C; Garcia-Lopez JL; Pedraza M; Garrido P;
TI -
Lastra E; Moyano A
Ifosfamide and vinorelbine in advanced platinum-resistant ovarian
cancer: excessive toxicity with a potentially active regimen.
SO - Gynecol Oncol 2002 Mar;84(3):368-73
AD - Medical Oncology Service, Alcala de Henares University, Madrid, 28034,
Spain. agonzalez@hrc.insalud.es
OBJECTIVES: The aim of this study was to determine the activity and
toxicity of a vinorelbine and ifosfamide combination in
platinum-resistant advanced ovarian cancer. PATIENTS AND METHODS:
Patients were treated with ifosfamide (2 g/m(2)/day) infused over 1 h x
3 days (with mesna uroprotection) and vinorelbine (30 mg/m(2)) on days 1
and 8. Treatment was repeated on a 21-day schedule. In order to avoid
unacceptable toxicity in this subset of patients where the chemotherapy
is mainly palliative, the Bryant and Day two-stage phase II trial design
incorporating toxicity considerations was chosen. A cutoff point for the
response rate (10%) and for severe toxicity (25%) was established for
11 paclitaxel and platinum-resistant patients and 1 potentially
platinum-sensitive patient were treated. Five patients (41%) experienced
grade 3-4 central nervous toxicity requiring hospital admission. In
accordance with the Bryant and Day design, the study was stopped early
because greater than 25% of the first 14 patients developed grade 3-4
neurotoxicity. A retrospective review of clinical characteristics of
these patients showed at least one well-known risk factor associated
with ifosfamide central toxicity. Hematological toxicity was common,
mainly grade 4 neutropenia, which was observed in all but 1 patient,
usually of short duration, and there were 4 episodes of neutropenic
fever. Ten patients were evaluated for response. Two complete responses
and 1 partial response according to CA-125 criteria were observed.
CONCLUSION: This combination may be active in platinum-resistant ovarian
cancer but the high toxicity encountered, principally neurotoxicity in
those with large central pelvic masses, means that further studies with
this schedule may not be warranted.
24
UI - 11890098
AU - Kim RY
TI -
Recent advances in the treatment of gynecologic malignancies: an
overview of the GOG phase III trials.
SO - Gan To Kagaku Ryoho 2002 Feb;29 Suppl 1():125-40
AD - Department of Radiation Oncology, Comprehensive Cancer Center,
University of Alabama at Birmingham, Birmingham, Alabama, USA.
25
UI - 11127118
AU - Wang PH; Yuan CC
TI -
Laparoscopic excision of ovarian dermoid cysts with controlled
intraoperative spillage: safety and effectiveness.
SO - J Reprod Med 2000 Nov;45(11):965-6
26
UI - 11751481
AU - Menon C; Kutney SN; Lehr SC; Hendren SK; Busch TM; Hahn SM; Fraker DL
TI -
Vascularity and uptake of photosensitizer in small human tumor nodules:
implications for intraperitoneal photodynamic therapy.
SO - Clin Cancer Res 2001 Dec;7(12):3904-11
AD - Harrison Department of Surgical Research, Hospital of the University of
Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
PURPOSE: i.p. spread of cancers is a common clinical problem, with
limited treatment options leading to morbidity and death. i.p.
photodynamic therapy (IP-PDT) combines maximal surgical debulking of
gross tumor with intraoperative light delivery to the peritoneum after
preoperative i.v. injection of photosensitizer to treat residual
disease. An issue of concern in IP-PDT is the potential lack of
photosensitizer uptake by residual small tumor nodules (STNs) < or =5 mm
in maximum diameter and by microscopic residual disease caused by
incomplete development of a vascular supply. This study examined the
existence of vasculature and Photofrin (PF) uptake in STNs in 12
patients in a Phase II clinical trial for IP-PDT. EXPERIMENTAL DESIGN:
Patients received PF 2.5 mg/kg i.v. 48 h before surgery. STNs obtained
during surgery were cryosectioned, immunostained for
platelet/endothelial cell adhesion molecule 1, and analyzed by light
microscopy. Mean vascular densities in STNs were determined by counting
microvessels within a x200 field (0.28 mm(2) area). Sections were also
examined for PF uptake by fluorescence image analysis using an
epifluorescence microscope and IPLab Spectrum software. RESULTS: Data
obtained showed that tumors as small as 1 mm in diameter stained
positive for platelet/endothelial cell adhesion molecule 1 and contained
PF. A negative control from a patient not given PF showed no detectable
fluorescence. The average of all mean vascular densities in STNs was
determined to be 100 +/- 29. CONCLUSIONS: We conclude that STNs, as
small as 1 mm in diameter, have a functional vasculature, because these
tumors show PF uptake after i.v. delivery. Both properties are crucial
for the treatment of residual STNs by IP-PDT after surgical debulking.
27
UI - 11589365
AU - Li QQ; Ding L; Reed E
TI -
Proteasome inhibition suppresses cisplatin-dependent ERCC-1 mRNA
expression in human ovarian tumor cells.
SO - Res Commun Mol Pathol Pharmacol 2000 May-Jun;107(5-6):387-96
AD - Medicine Branch, Division of Clinical Sciences, National Cancer
Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
qli001@umaryland.edu
One of the major problems with ovarian cancer treatment is the clinical
development of resistance to cisplatin. Considerable efforts have been
directed toward the identification of biological and pharmacological
agents that would reverse drug resistance to cisplatin. ALLnL is an
inhibitor of the proteasome that can inhibit the ubiquitin-proteasome
pathway, which plays an essential role in many processes in cell life.
We have recently shown that ALLnL, at concentrations that do not appear
harmful, has significantly enhanced DNA platination and decreased DNA
repair of cisplatin-DNA adducts in human A2780/CP70 ovarian carcinoma
cells. These activities of proteasome inhibition were also associated
with substantially increased cisplatin toxicity in these cells. In this
communication, we demonstrate that treatment of A2780/CP70 cells with
ALLnL blocks cisplatin-induced ERCC-1 mRNA expression in a
concentration- and time-dependent manner, as measured by Northern blot
analysis. In addition, we showed that the cisplatin-dependent increase
in steady-state levels of ERCC-1 mRNA was prevented by pretreatment with
lactacystin, a potent and specific inhibitor of proteasome. These
results suggest that the effect of proteasome inhibition on cisplatin
cytotoxicity, DNA platination, and DNA repair of cisplatin adducts in
ovarian cancer cells may be through down-regulating ERCC-1 expression.
28
UI - 11821450
AU - Barakat RR; Sabbatini P; Bhaskaran D; Revzin M; Smith A; Venkatraman E;
TI -
Aghajanian C; Hensley M; Soignet S; Brown C; Soslow R; Markman M;
Hoskins WJ; Spriggs D
Intraperitoneal chemotherapy for ovarian carcinoma: results of long-term
follow-up.
SO - J Clin Oncol 2002 Feb 1;20(3):694-8
AD - Gynecology Service, Department of Surgery, Gynecology Disease Management
Team, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
gynbreast@mskcc.org
PURPOSE: To determine long-term survival and predictors of recurrence in
a retrospective cohort of patients with epithelial ovarian cancer
treated with intraperitoneal (IP) chemotherapy. PATIENTS AND METHODS:
Records were reviewed of 433 patients who received IP therapy for
ovarian cancer between 1984 and 1998; follow-up data were available for
411 patients. IP therapy was provided as consolidation therapy (n = 89),
or for treatment of persistent (n = 310) or recurrent (n = 12) disease
after surgery and initial systemic therapy; therapy usually consisted of
platinum-based combination therapy. Statistical analysis included tests
for associations between potential prognostic factors, and between
prognostic factors and survival. Survival probabilities were estimated
by Kaplan-Meier methods, and prognostic factors for survival were
evaluated by a Cox proportional hazard model. RESULTS: The mean age of
patients was 52 years (range, 25 to 76 years). Distribution by stage and
grade was as follows: stage I, 7; II, 24; III, 342; IV, 52; not
available (NA), 8; and grade 1, 30; 2, 99; and 3, 289; NA, 15. The
median survival from initiation of IP therapy by residual disease was
none, 8.7 years; microscopic, 4.8 years; less than 1 cm, 3.3 years; more
than 1 cm, 1.2 years. In a multivariate analysis, the only significant
predictors of long-term survival were grade and size of residual disease
at initiation of IP therapy. CONCLUSION: Prolonged survival was observed
in selected patients receiving IP platinum-based therapy. It is not
possible to determine the contribution of IP therapy to survival in this
study. A relationship between size of disease at the initiation of IP
therapy and long-term survival was demonstrated.
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