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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Ovarian Cancer - August 2002
National Cancer Institute®
Last Modified: August 1, 2002
- Synergy between the non-classical thymidylate synthase inhibitor AG337 (Thymitaq) and cisplatin in human colon and ovarian cancer cells.
- Physiologic and pathologic drug resistance in ovarian carcinoma--a hypothesis based on a clonal progression model.
- Predicting response of ovarian cancer to paclitaxel treatment based on trend analysis of serum CA125.
- Weekly cisplatin and oral etoposide as treatment for relapsed epithelial ovarian cancer.
- Postsurgical pelvis: treatment follow-up.
- Influence of Cremophor El on the bioavailability of intraperitoneal paclitaxel.
- Role of chemotherapy in the management of ovarian cancer.
- Novel target antigens for dendritic cell-based immunotherapy against ovarian cancer.
- Adjuvant radiotherapy in stage I-II epithelial ovarian cancer.
- Drug resistance in epithelial ovarian cancer: P-glycoprotein and glutation S-transferase. Can they play an important role in detecting
- [Treatment of ovarian cancer]
- [New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]
- Chemotherapy versus hormonal treatment in platinum- and paclitaxel-refractory ovarian cancer: a randomised trial of the German
- Multicentre phase II study of oxaliplatin as a single-agent in cisplatin/carboplatin +/- taxane-pretreated ovarian cancer patients.
- Cost effectiveness of paclitaxel/cisplatin compared with cyclophosphamide/cisplatin in the treatment of advanced ovarian cancer
- Micropapillary serous ovarian carcinoma: surgical management and clinical outcome.
- Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based chemotherapy for patients with ovarian cancer.
- Treatment preferences in recurrent ovarian cancer.
- Psychological impact of prophylactic oophorectomy in women at increased risk of developing ovarian cancer: a prospective study.
- Low proliferation activity may be associated with chemoresistance in clear cell carcinoma of the ovary.
- Mechanisms of cisplatin resistance in clear cell carcinoma of the ovary.
- Stromal therapy: the next step in ovarian cancer treatment.
- A rationale for the clinical development of the thymidylate synthase inhibitor ZD9331 in ovarian and other solid tumours.
- Treating relapsed epithelial ovarian cancer with luteinizing hormone-releasing agonist (goserelin) after failure of chemotherapy.
- Expanding horizons: an update on the use of docetaxel in non-small cell lung, ovarian, and breast cancers.
- Docetaxel in ovarian cancer: phase III perspectives and future development.
Table of Contents
1
UI - 8949986
AU - Raymond E; Djelloul S; Buquet-Fagot C; Mester J; Gespach C
TI -
Synergy between the non-classical thymidylate synthase inhibitor AG337
(Thymitaq) and cisplatin in human colon and ovarian cancer cells.
SO - Anticancer Drugs 1996 Sep;7(7):752-7
AD - Unite INSERM U55, Institut Federatif de Recherches du Centre
Hospitalo-Universitaire Paris Saint-Antoine, Hopital Saint-Antoine,
France.
AG337 is the recent non-classical thymidylate synthase inhibitor with
promising activity and manageable toxicity in phase I clinical trials.
In this study, we investigated the cytotoxic activity of AG337 alone and
in combination with cisplatin in cultured human colon (HT29) and ovarian
(2008) cancer cell lines and their derived counterparts selected for
their resistance to 5-fluorouracil (5-FU) (HT29-5-FU) and cisplatin
(2008C13). We observed that AG337 had potent cytotoxic effects in colon
(IC50 = 0.17 MicroM) and ovarian cancer cells (IC50 = 0.65 microM). The
cytotoxic activity of AG337 was higher than that of 5-FU in the two
models. The Activity of AG337 was not significantly affected in
5-FU-resistant HT29-5-FU colon cancer cells characterized by an
amplification of the thymidylate synthase gene (IC50 = 0.27 microM, p =
0.15). Combinations of cisplatin and AG337 exert synergistic activity in
both ovarian and colon cancer cells. Interestingly, this synergism was
maintained in 5-FU- and cisplatin-resistant cells. Therefore, our data
encourage further examination of combinations of AG337 with cisplatin in
cancer chemotherapy.
2
UI - 10050979
AU - Pusztai L; Siddik ZH; Mills GB; Bast RC Jr
TI -
Physiologic and pathologic drug resistance in ovarian carcinoma--a
hypothesis based on a clonal progression model.
SO - Acta Oncol 1998;37(7-8):629-40
AD - University of Texas, MD Anderson Cancer Center, Division of Medicine,
Houston 77030, USA.
Conventional models for successful chemotherapy suggest that early-stage
ovarian cancer should be more responsive to cytotoxic drugs than
advanced disease, that multiple drugs will prove more efficacious than
single agents and that more intensive chemotherapy will prove superior
to conventional doses. The purpose of numerous clinical studies has been
to test these predictions and the results often fall short of the
expectations. In trials to date, adjuvant chemotherapy for high-risk,
early-stage ovarian cancer has provided only a modest, equivocal
increase in disease-free survival. Combination chemotherapy produces
higher response rates but this has not consistently resulted in
prolonged survival. Dose intensification with high-dose chemotherapy
increases rate of response further, but most responses are of short
duration. The objective of this review is to integrate clinical and
molecular biological observations into a novel model of drug resistance.
We hypothesize that drug sensitivity is an acquired characteristic of
neoplastic cells, and that there are two broad cellular forms of
resistance to cytotoxic drugs. 'Physiological drug resistance' is a
cellular state when drug sensitivity of cancer cells is similar to that
of the corresponding normal tissue. This form of drug resistance can
precede the acquisition of drug sensitivity and may be predominant in
the early stages of neoplastic progression. A distinct, 'pathological
drug resistance' can reappear later during tumor progression or during
chemotherapy as a result of increased detoxification, upregulation of
repair pathways or defective apoptosis. Tumors are formed of
heterogeneous cell populations and in terms of drug sensitivity three
distinct cell types may be present: drug-sensitive, physiologically
drug-resistant and pathologically drug-resistant. Clinical response to
chemotherapy is determined by the relative contribution of these
different cell populations to the total cellular mass. Depending on the
predominant type of surviving population, distinct patterns of clinical
failure may develop that require different treatment strategies for
optimal management. For chemosensitive cells that survived insufficient
chemotherapy, consolidation with further, perhaps, high-dose
chemotherapy is a rational option. For pathologically drug-resistant
cells, pharmacological manipulation of drug resistance, and signaling
pathways in combination with chemotherapy could be exploited. For
physiologically drug-resistant cells, non-chemotherapy-based,
'chemopreventive' strategies to arrest tumor progression may prove
beneficial.
3
UI - 12142397
AU - Nekulova M; Pecen L; Kalabova R; Simickova M; Topolcan O; Pikner R;
TI -
Vondracek V; Valik D
Predicting response of ovarian cancer to paclitaxel treatment based on
trend analysis of serum CA125.
SO - Clin Chem 2002 Aug;48(8):1364-7
AD - Department of Laboratory Medicine, Masaryk Memorial Cancer Institute,
Zluty kopec 7, 656 65 Brno, The Czech Republic.
4
UI - 11843248
AU - Meyer T; Nelstrop AE; Mahmoudi M; Rustin GJ
TI -
Weekly cisplatin and oral etoposide as treatment for relapsed epithelial
ovarian cancer.
SO - Ann Oncol 2001 Dec;12(12):1705-9
AD - Department of Medical Oncology, Mount Vernon Hospital, Northwood, UK.
BACKGROUND: Response rates to chemotherapy in relapsed, platinum
resistant epithelial ovarian cancer remain poor. We have explored the
effectiveness of weekly cisplatin combined with prolonged oral etoposide
in this patient group. PATIENTS AND METHODS: Forty-two women with
relapsed, advanced ovarian cancer were treated with cisplatin 60 mg/m2
on days 1, 8, 15, 29, 36 and 43 and oral etoposide 50 mg given from day
1-14 and day 29-43. In those who were responding and tolerating
treatment (n = 13) oral etoposide 50 mg was continued for two further
cycles (days 1-21 repeated every 28 days). The interval since last
platinum containing chemotherapy was > 6 months in 28 patients and < 6
months in 16 patients. RESULTS: Thirty-six patients were evaluable for
response according to CA 125 criteria giving an overall response rate of
44%. The response rate in evaluable patients declined with increasing
numbers of previous treatments: 57% with one prior treatment, 42% with
two, 40% with three or more. The response rate in patients who had
received platinum chemotherapy within six months prior to treatment was
46%. The only significant non-haematological toxicity was nausea and
vomiting in 4 patients who experienced greater than grade 2 toxicity.
The number of patients experiencing haematological toxicity more than
grade 2 was as follows: haemoglobin 3, white blood count 12, platelets
6. Sixteen patients had dose delays and two had dose reductions.
CONCLUSION: We conclude that this short but intensive regimen provides
worthwhile response rates, even in those patients who would ordinarily
be considered refractory to platinum, and has an acceptable toxicity
profile.
5
UI - 12117198
AU - Sugimura K; Okizuka H
TI -
Postsurgical pelvis: treatment follow-up.
SO - Radiol Clin North Am 2002 May;40(3):659-80, viii
AD - Department of Radiology, Kobe University Graduate School of Medicine,
Japan. sugimura@kobe-u.ac.jp
Imaging for recurrence and complications of gynecologic malignancies
following treatment with radical hysterectomy, chemotherapy, and
radiation therapy has become an important determinant for treatment
options available to patients. MR imaging and computed tomography can be
used to provide evidence of limited local disease recurrence and thereby
identify disease that is still potentially curable with adjuvant
treatments. This article examines the imaging modalities currently used
to detect recurrence and assist in making treatment changes for
gynecologic malignancies and presents specific patient findings
following definitive primary treatment of uterine cancer and ovarian
cancer with radical hysterectomy, radiation therapy, or chemotherapy.
6
UI - 11948138
AU - Gelderblom H; Verweij J; van Zomeren DM; Buijs D; Ouwens L; Nooter K;
TI -
Stoter G; Sparreboom A
Influence of Cremophor El on the bioavailability of intraperitoneal
paclitaxel.
SO - Clin Cancer Res 2002 Apr;8(4):1237-41
AD - Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den
Hoed Kliniek) and University Hospital Rotterdam, 3075 EA Rotterdam, the
Netherlands.
It has been hypothesized that the paclitaxel vehicle Cremophor EL (CrEL)
is responsible for nonlinear drug disposition by micellar entrapment. To
gain further insight into the role of CrEL in taxane pharmacology, we
studied the pharmacokinetics of paclitaxel in the presence and absence
of CrEL after i.p. and i.v. dosing. Patients received an i.p. tracer
dose of [G-(3)H]paclitaxel in ethanol without CrEL (100 microCi diluted
further in isotonic saline) on day 1, i.p. paclitaxel formulated in CrEL
(Taxol; 125 mg/m(2)) on day 4, an i.v. tracer of [G-(3)H]paclitaxel on
day 22, and i.v. Taxol (175 mg/m(2)) on day 24. Four patients (age
range, 54-74 years) were studied, and serial plasma samples up to 72 h
were obtained and analyzed for total radioactivity, paclitaxel, and
CrEL. In the presence of CrEL, i.v. paclitaxel clearance was 10.2 +/-
3.76 liters/h/m(2) (mean +/- SD), consistent with previous findings. The
terminal disposition half-life was substantially prolonged after i.p.
dosing (17.0 +/- 11.3 versus 28.7 +/- 8.72 h), as was the mean residence
time (7.28 +/- 2.76 versus 40.7 +/- 13.8 h). The bioavailability of
paclitaxel was 31.4 +/- 5.18%, indicating insignificant systemic
concentrations after i.p. treatment. CrEL levels were undetectable after
i.p. dosing (<0.05 microl/ml), whereas after i.v. dosing, the mean
clearance was 159 +/- 58.4 ml/h/m(2), in line with earlier observations.
In the absence of CrEL, the bioavailability and systemic concentrations
of i.p. paclitaxel were significantly increased. This finding is
consistent with the postulated concept that CrEL is largely responsible
for the pharmacokinetic advantage for peritoneal cavity exposure to
total paclitaxel compared with systemic delivery.
7
UI - 12113074
AU - Markman M
TI -
Role of chemotherapy in the management of ovarian cancer.
SO - Expert Rev Anticancer Ther 2002 Feb;2(1):90-6
AD - Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195,
USA. markmam@ccf.org
Ovarian cancer is a highly chemotherapy-sensitive malignancy. With
current treatment, most women presenting with advanced disease will
achieve an objective response and experience major and sustained
improvement of cancer-related symptoms. Unfortunately, the majority of
patients will ultimately recur, such that second-line treatment options
will need to be considered. Further complicating the decision-making
process in choosing an 'optimal' second-line regimen is a serious
paucity of randomized trials in this clinical setting.
8
UI - 12113075
AU - Cannon MJ; O'Brien TJ; Underwood LJ; Crew MD; Bondurant KL; Santin AD
TI -
Novel target antigens for dendritic cell-based immunotherapy against
ovarian cancer.
SO - Expert Rev Anticancer Ther 2002 Feb;2(1):97-105
AD - Department of Obstetrics and Gynecology, University of Arkansas for
Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA.
cannonmartin@uams.edu
Identification of tumor-specific target antigens has been a major hurdle
for the treatment of malignant disease by vaccination or immunotherapy.
A second challenge has been the induction of therapeutically effective
immune responses to these 'self' antigens. The recent recognition of
dendritic cells as powerful antigen-presenting cells capable of inducing
primary T-cell responses in vitro and in vivo--in combination with
identification of tumor-specific antigens--has generated widespread
interest in dendritic cell-based immunotherapy against a wide variety of
tumors. In this review, a series of recently identified novel ovarian
tumor antigens is discussed, and the potential for therapeutic dendritic
cell vaccination targeted against these antigens is assessed.
9
UI - 11874070
AU - Skirnisdottir I; Sorbe B
TI -
Adjuvant radiotherapy in stage I-II epithelial ovarian cancer.
SO - Eur J Gynaecol Oncol 2001;22(6):409-16
AD - Department of Gynecology and Obstetrics, University Hospital, Uppsala,
Sweden.
OBJECTIVE: The purpose of this study was to assess the efficacy and
side-effects of abdominopelvic irradiation applied as adjuvant
postoperative therapy in early stage ovarian carcinomas. METHODS: From 1
epithelial ovarian carcinoma were treated with postoperative
radiotherapy. Whole abdominal irradiation or lower abdominopelvic
irradiation was used. The dose of specification was 20 Gy to the upper
part of the abdominal cavity and 40 Gy to the lower part of the abdomen
and the pelvic region. RESULTS: Primary cure was achieved in 110
patients (97%). During the period of follow-up, 33 cases of tumor
recurrences (30%) were recorded. Abdominopelvic metastases were most
frequent (18%). The overall 5-year survival rate for the complete series
was 69% and the cancer-specific survival rate was 72%. Tumor grade was
an independent and significant prognostic factor (Cox multivariate
analysis; p = 0.007). Early radiation reactions of any type were noted
in 93% of the cases and, in 11%, discontinuation of radiotherapy was
necessary. Late radiation reactions were noted in 58% of the cases and
the most common side-effect was diarrhea, but in most cases these
reactions were of limited clinical significance. The incidence of severe
bowel toxicity was 10% and, in two patients ( 1.8%), surgery was
necessary due to late radiation reactions. CONCLUSIONS: Adjuvant
abdominopelvic radiotherapy is one option among others (e.g. various
types of chemotherapy or no further treatment) in primary treatment of
early stage ovarian carcinoma. The optimal adjuvant therapy for this
group of patients is not known today and further prospective and
randomized studies are needed.
10
UI - 11878288
AU - Simsek T; Ozbilim G; Gulkesen H; Kaya H; Sargin F; Karaveli S
TI -
Drug resistance in epithelial ovarian cancer: P-glycoprotein and
glutation S-transferase. Can they play an important role in detecting
response to platinum-based chemotherapy as a first-line therapy.
SO - Eur J Gynaecol Oncol 2001;22(6):436-8
AD - Department of Obstetrics and Gynecology, Akdeniz University School of
Medicine, Antalya, Turkey.
OBJECTIVE: Drug resistance is important for the treatment of ovarian
cancer. P-glycoprotein and glutation S-transferase as resistance markers
play an important role in the effectivity of chemotherapeutical agents.
The role of P-glycoprotein and glutation S-transferase in the treatment
of epithelial ovarian cancer is not well understood. We investigated the
relation between P-glycoprotein and glutation S-transferase level for
response to platinum-based chemotherapy in epithelial ovarian cancer.
MATERIAL AND METHODS: We reviewed 30 cases diagnosed as epithelial
ovarian cancer and treated with platinum-based chemotherapy in the
Department of Obstetrics and Gynecology, Akdeniz University School of
Medicine. The material was attained from initial parafin-embeded blocks
stained for P-glycoprotein and glutation S-transferase. The cases that
were diagnosed and treated before attending our clinic were not enrolled
in the study. RESULTS: Mean age was 58.2 (25-70) and mean gravida 4.1
(0-10). Twenty-four patients (80%) were glutation S-transferase
positive. Three cases (10%) out of 30 had positive reaction for
P-glycoprotein. No difference was revealed regarding chemotherapy
response rate among the cases showing glutation S-transferase positivity
and P-glycoprotein negativity. CONCLUSION: Detection of glutation
S-transferase and P-glycoprotein levels in epithelial ovarian cancer
tissue is not important for response to platinum-based chemotherapy as a
first line.
11
UI - 12078339
AU - Cianti C
TI -
[Treatment of ovarian cancer]
SO - Clin Ter 2002 Mar-Apr;153(2):135-44
AD - Ospedale S. Spirito in Sassia, Roma, Italia.
PURPOSE: To present an approach to the treatment of epithelial ovarian
cancer. DESIGN: A large number of studies in ovarian cancer have been
reviewed. RESULTS: Ovarian cancer is the most common fatal malignancy of
the female genital tract. The high mortality is due to the fact that the
most part of patients are diagnosed with advanced disease. Cytoreductive
surgery followed by platinum-based chemotherapy is the standard
therapeutic strategy for patients with advanced ovarian cancer.
Postsurgical residual disease is the most important prognostic factor.
The combination of Paclitaxel and Cisplatin or Carboplatin is currently
accepted as the standard chemotherapy for advanced ovarian cancer.
Second- look laparatomy should be reserved to patients enrolled in
clinical trial. Resistant disease remain the major cause of relapse and
death. Several drugs have been employed in second-line therapy; however,
the responses are generally short and survival is poor. CONCLUSIONS:
Future research should include new drugs or new combination regimens to
improve clinical outcomes and overall survival.
12
UI - 11935494
AU - Costa SD; von Minckwitz G; Wernicke K; Kaufmann M
TI -
[New aspects by the therapy of ovarian cancer--What changes after the
ASCO-Meeting 2001]
SO - Zentralbl Gynakol 2002 Feb;124(2):96-103
AD - Zentrum der Frauenheilkunde und Geburtshilfe, Goethe-Universitat
Frankfurt am Main, Germany.
The standard primary therapy of advanced ovarian cancer consists of
platinum derivatives in combination with paclitaxel. In a first report
presented at this year's meeting of the American Society of Clinical
Oncology (ASCO) docetaxel appeared to be as effective as paclitaxel in
combination with carboplatin, while the toxicity profile present some
advantages. The addition of a third drug to platinum-taxane-combination
does not appear to improve the therapeutic index. According to the data
of the ICON1- and ACTION-trial, carboplatin containing chemotherapies
are associated with a significant benefit also in early ovarian cancer.
Platinum-resistant disease remains a therapeutic challenge, since the
available drugs display only limited activity of short duration. Some
experimental data suggest evidence for a possible therapeutic role of
small molecules that inhibit the epidermal growth factor receptor
(OSI-774) or antisense oligonucleotides interfering with EGF-receptor
signalling (ISIS 5132). Novel classes of chemotherapeutic agents,
including the acylfulvenes and the epothilone-analogues warrant further
study in this disease. Multimodal therapies combining cytotoxic agents
with antibodies against CA 12-5 or metalloproteinase inhibitors have
failed to demonstrate any survival benefit in patients with ovarian
cancer. Despite significant progress in the last decade ovarian cancer
remains the most lethal gynaecologic malignancy in women in most western
countries. Further multicenter clinical studies are needed to better
define new therapeutic options.
13
UI - 11886002
AU - du BA; Meier W; Luck HJ; Emon G; Moebus V; Schroeder W; Costa S;
TI -
Bauknecht T; Olbricht S; Jackisch C; Richter B; Wagner U
Chemotherapy versus hormonal treatment in platinum- and
paclitaxel-refractory ovarian cancer: a randomised trial of the German
Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group Ovarian
Cancer.
SO - Ann Oncol 2002 Feb;13(2):251-7
AD - Department of Gynecology & Gynecologic Oncology,
Dr-Horst-Schmidt-Kliniken Wiesbaden, Germany.
dubois.hsk-wiesbaden@uumail.de
BACKGROUND: The majority of patients with ovarian cancer are not cured
by first-line treatment. Until now, no study could demonstrate any
substantial benefit when exposing ovarian cancer patients to second-line
chemotherapy. However, most treatment regimens induce toxicity, thus
negatively influencing the quality of rather limited life spans. Here we
evaluate whether a second-line chemotherapy can offer any benefit
compared with a less toxic hormonal treatment. PATIENTS AND METHODS:
Patients with ovarian cancer progressing during platinum-paclitaxel
containing first-line therapy or experiencing relapse within 6 months
were eligible. Patients were stratified for response to primary
treatment (progression versus no change/response), and measurable versus
non-measurable disease. Treatment consisted of either treosulfan 7 g/m5
infused over 30 min or leuprorelin 3.75 mg injected subcutaneously or
intramuscularly. Both regimens were repeated every 4 weeks. RESULTS:
This study began in late 1996, and after 2.5 years accrual an interim
analysis was performed when several investigators reported their concern
about a suspected lack of efficacy. Following this analysis the
recruitment was stopped early and the 78 patients already enrolled were
followed up. The majority of patients received treatment until
progressive disease was diagnosed or death occurred. Treatment delay was
observed rarely and dose reduction was performed only in the treosulfan
arm in 5% of 150 courses. Overall, both treatment arms were well
tolerated. No objective responses were observed. The median survival
time was 36 and 30 weeks in the treosulfan and leuprorelin arms,
respectively. Overall survival did not differ between patients with
relapse 3-6 months after first-line chemotherapy compared with patients
with progressive disease within 3 months. CONCLUSIONS: The selected
patient population represents a subgroup with extremely poor prognosis.
Accordingly, results were not impressive. Both treatment arms showed
favourable toxicity data, but failed to show remarkable activity, thus
adding only limited evidence to the issue of whether patients with
refractory ovarian cancer might benefit from second-line chemotherapy.
Even stratified analysis did not identify any subgroup of patients in
whom the administration of second-line chemotherapy could demonstrate a
clinically relevant survival benefit.
14
UI - 11886003
AU - Dieras V; Bougnoux P; Petit T; Chollet P; Beuzeboc P; Borel C; Husseini
TI -
F; Goupil A; Kerbrat P; Misset JL; Bensmaine MA; Tabah-Fisch I;
Pouillart P
Multicentre phase II study of oxaliplatin as a single-agent in
cisplatin/carboplatin +/- taxane-pretreated ovarian cancer patients.
SO - Ann Oncol 2002 Feb;13(2):258-66
AD - Institut Curie, Paris, France. veronique.dieras@curie.net
BACKGROUND: This multicentre phase II open-label study evaluated safety
and antitumour activity of oxaliplatin in cisplatin or carboplatin
(cis/carboplatin) +/- taxane-pretreated advanced ovarian cancer (AOC)
patients. PATIENTS AND METHODS: Forty-eight patients received
oxaliplatin 130 mg/M2 intravenously every 3 weeks, 94% having a
performance status (PS) 0-1. All were pretreated with cis/carboplatin
and 21 (44%) with paclitaxel. The median number of involved organs was
two, 18 (38%) had liver metastasis, 23 (48%) were platinum-resistant and
14 (29%) were taxane-resistant. Forty-two patients were evaluable for a
response, 18 (43%) were platinum-resistant and 11 (26%) were
taxane-resistant. RESULTS: A total of 253 cycles was administered
(median: 5.5/patient). Median cumulative oxaliplatin dose was 666 mg/m2.
National Cancer Institute-Common Toxicity Criteria toxicity analysis
showed that seven patients (15%) had grade 3/4 thrombocytopenia, two
patients (4%) had grade 3 neutropenia, and one patient had grade 3
anaemia. Eleven patients (23%) experienced grade 3 neurosensory
toxicity. Of the 29 patients with peripheral neuropathy at the end of
treatment, 55% had recovered or improved 1 month later. Eleven objective
responses (two complete) were obtained in the 42 evaluable patients [ORR
26%, 95% confidence interval (CI) 14% to 42%], with 10/24 (42%, 95% CI
22% to 63%) in platinum-sensitive, and 1 of 18 (5.6%, 95% CI 0% to 27%)
in platinum-resistant patients. Median response duration was 9.2 months
(95% CI 6.6% to 11.8%), and median progression-free and overall survival
in all treated patients were 4.3 months (95% CI 3.0% to 5.7%) and 15.0
months (95% CI 11.1% to 18.8%), respectively. CONCLUSION: Oxaliplatin
has a good safety profile and is active in cis/carboplatin +/-
paclitaxel-pretreated AOC patients.
15
UI - 12093304
AU - Neymark N; Gorlia T; Adriaenssen I; Baron B; Piccart M
TI -
Cost effectiveness of paclitaxel/cisplatin compared with
cyclophosphamide/cisplatin in the treatment of advanced ovarian cancer
in Belgium.
SO - Pharmacoeconomics 2002;20(7):485-97
AD - European Organization for Research and Treatment of Cancer (EORTC) Data
Center, Health Economics Unit, bte. 11, Avenue E. Mounier 83, B-1200
Brussels, Belgium.
OBJECTIVE: To assess the economic impact of two polychemotherapy
regimens for patients with advanced ovarian cancer from the perspective
of the Belgian health insurance and financing system. DESIGN: An
economic evaluation was integrated in an intergroup randomised
controlled trial (EORTC 55931) in which patients were randomised to
receive the new treatment of paclitaxel and cisplatin or the standard
therapy of cyclophosphamide and cisplatin. Data on the use of medical
resources were collected prospectively for the 231 European Organization
for Research and Treatment of Cancer (EORTC) patients in the trial and
costs were valued by using unit prices. The outcome for the economic
evaluation was mean survival time as determined by the so-called
restricted means method, with the time point of restriction fixed by
statistical criteria. A correction of censoring of the cost data
collected in the trial was also performed. MAIN OUTCOME MEASURES AND
RESULTS: The paclitaxel and cisplatin group experienced a statistically
significant improvement in mean survival time of 4 months, which was
associated with an increase in the average total cost per patient of
6795 euros (EUR; 1998 values), when costs were assessed over the same
period as the gain in mean survival time. This corresponds to a point
estimate of the incremental cost-effectiveness ratio of EUR20 385 per
life-year gained. The impact of uncertainty was assessed by using a
bias-corrected and accelerated bootstrap method with 5000 resamples, and
the final results of the analysis are expressed in terms of a
cost-effectiveness acceptability curve. CONCLUSIONS: The present
economic evaluation has shown that the substitution of paclitaxel for
cyclophosphamide in the chemotherapy regimen for women with advanced
ovarian cancer leads to a significant improvement in patient survival,
which is associated with an increase in costs for the Belgian health
insurance system.
16
UI - 12144823
AU - Bristow RE; Gossett DR; Shook DR; Zahurak ML; Tomacruz RS; Armstrong DK;
TI -
Montz FJ
Micropapillary serous ovarian carcinoma: surgical management and
clinical outcome.
SO - Gynecol Oncol 2002 Aug;86(2):163-70
AD - The Kelly Gynecologic Oncology Service, Department of Gynecology and
Obstetrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland
21287, USA. rbristo@jhmi.edu
OBJECTIVES: The objectives of this study were to characterize the
prognostic features of micropapillary serous ovarian carcinoma (MPSC),
examine the clinical impact of surgical staging, and define the role of
cytoreductive surgery for patients with advanced disease. METHODS:
Fifty-one patients with MPSC were identified from hospital and tumor
registry databases. Demographic, operative, pathologic, and follow-up
data were abstracted retrospectively. Survival curves were generated
using the Kaplan-Meier method, and statistical comparisons were
performed using the log rank test, logistic regression analysis, and the
Cox proportional hazards regression model. RESULTS: The median age at
diagnosis was 45 years, and follow-up extended to a median of 43.0
months. Stage I/II disease was present in 25.5% of patients and no
disease-related deaths were observed in this group. Stage III disease
was discovered in 29.4% of patients with tumor clinically confined to
the ovaries. Stage III/IV disease (74.5% of cases) was associated with
median progression-free and overall survival times of 32.8 and 114.2
months, respectively. Menopausal status and the anatomic extent of
disease were significantly associated with survival outcome. However,
the strongest independent predictor of survival for patients with
advanced disease was the amount of residual tumor. Median overall
survival for patients with optimal cytoreduction (residual disease 1 cm
residual tumor (P < 0.0002). CONCLUSIONS: MPSC carries a significant
risk of extraovarian spread; however, adequately sampled Stage I/II
disease is associated with a favorable prognosis. Optimal cytoreduction
is associated with improved survival and should be the primary
therapeutic objective for patients with advanced-stage MPSC.
17
UI - 12144824
AU - Kamazawa S; Kigawa J; Kanamori Y; Itamochi H; Sato S; Iba T; Terakawa N
TI -
Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based
chemotherapy for patients with ovarian cancer.
SO - Gynecol Oncol 2002 Aug;86(2):171-6
AD - Department of Obstetrics and Gynecology, Tottori University School of
Medicine, Yonago, 683-8504, Japan.
OBJECTIVE: The objective of this study was to determine the relationship
between multidrug resistance and sensitivity to paclitaxel (PTX) in
ovarian cancer. METHODS: We used human ovarian adenocarcinoma cell
lines, KF, a PTX-resistant cell line (KFTx), SK-OV-3, and KOC7c.
Additionally, 27 patients with ovarian cancer who had residual disease
were examined. All patients underwent postoperative chemotherapy
consisting of 175 mg/m(2) PTX and area under curve (AUC) 5 carboplatin.
The sensitivity of the cells to PTX or cisplatin (CDDP) was determined
by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
assay. mRNA expression of multidrug resistance gene-1 (MDR-1) and
multidrug resistance-associated protein-1 (MRP-1) and MRP-2 was
determined by reverse transcription-polymerase chain reaction.
beta-Tubulin polymerization and Bcl-2 phosphorylation were examined by
Western blot analysis. RESULTS: Compared with KF, the IC(50) to PTX was
5.5-fold higher for KFTx, 0.3-fold for SK-OV-3, and 52.1-fold for KOC7c.
The IC(50) to CDDP was 0.7-, 4.2-, and 5.8-fold, respectively.
Expression of the MDR-1 gene was clearly observed in KFTx and KOC7c.
Expression of MRP-1 was observed in SK-OV-3 and KOC7c. Expression of
MRP-2 was detected only in KOC7c. CDDP enhanced beta-tubulin
polymerization induced by PTX in CDDP-sensitive cells. Bcl-2
phosphorylation appeared after exposure to IC(50) PTX in all cells.
Twenty-one patients responded to chemotherapy and six did not.
Expression of the MDR-1 gene for nonresponders was significantly higher
than that for responders (260.0 +/- 191.6 vs 9.3 +/- 21.8). With the
cutoff value of MDR-1 expression at 100, the predictive value for
chemoresponse was 96%. Expression of the MRP-1 and MRP-2 genes did not
differ between nonresponders and responders. CONCLUSION: MDR-1 gene
expression may be a useful predictor for PTX-based chemotherapy.
18
UI - 12144829
AU - Donovan KA; Greene PG; Shuster JL; Partridge EE; Tucker DC
TI -
Treatment preferences in recurrent ovarian cancer.
SO - Gynecol Oncol 2002 Aug;86(2):200-11
AD - Department of Psychology, University of Alabama at Birmingham, 35294,
USA.
OBJECTIVES: In the case of recurrent ovarian cancer, salvage therapy
represents the potential to trade off between quality and quantity of
life. Patient and physician face a choice between chemotherapy directed
at slowing disease progression and supportive or palliative care that
focuses on symptom management. To date, no studies have investigated the
effects of best supportive care on ovarian cancer patients' quality of
life and length of life as compared to salvage therapy. In other
cancers, both quantity and quality of life considerations have been
shown to affect treatment preferences. METHODS: Using a decision board,
we assessed preferences for salvage therapy or palliative care in the
case of recurrent ovarian cancer among 81 ovarian cancer patients
receiving first-line chemotherapy and 75 Noncancer Controls. RESULTS:
Compared to Noncancer Controls, ovarian cancer patients overwhelmingly
preferred salvage therapy; quantity of life was of primary importance.
In both groups, preference was not related to age, marital status,
number of children, or employment status. On average, patients indicated
they would switch from salvage therapy to palliative care when the
median survival associated with salvage therapy was reduced to 5 months.
Noncancer Controls would switch significantly sooner, when the median
increment in survival period was reduced to 8 months. Switchpoint was
not associated with life satisfaction, quality of life, or psychological
or spiritual well-being in either group. CONCLUSIONS: The majority of
women, independent of a cancer diagnosis, indicated a desire for
continuing aggressive treatment, despite poor outcomes. Quality of life
was of secondary importance, especially among ovarian cancer patients.
19
UI - 12144830
AU - Tiller K; Meiser B; Butow P; Clifton M; Thewes B; Friedlander M; Tucker
TI -
K
Psychological impact of prophylactic oophorectomy in women at increased
risk of developing ovarian cancer: a prospective study.
SO - Gynecol Oncol 2002 Aug;86(2):212-9
AD - Department of Medical Oncology, Prince of Wales Hospital, Sydney,
Australia. k.tiller@unsw.edu.au
OBJECTIVES: The objectives of this study were twofold: to prospectively
assess whether expressed intention to undergo prophylactic oophorectomy
translated into uptake and to evaluate the psychological impact of the
procedure in a sample of unaffected women with a strong family history
of breast/ovarian cancer. METHODS: Ninety-five women, initially assessed
at the time of their first attendance at a familial cancer clinic, were
followed-up 3 years later. A total of 22 women (23.2%) in this study had
undergone a prophylactic oophorectomy. Ten women (10.5%) who had
undergone a prophylactic oophorectomy during the 3-year follow-up period
were compared to 73 women (76.9%) who did not have a prophylactic
oophorectomy. Twelve women (12.6%) who had the procedure prior to study
entry were also assessed for psychological adjustment and associated
information needs. RESULTS: Age emerged as a significant predictor of
uptake of prophylactic oophorectomy (chi(2) = 7.13, P = 0.009). Among
those who had the procedure after study entry, a significant reduction
in ovarian cancer anxiety was observed (Z = -2.19, P = 0.029). Of the 22
women who had undergone a prophylactic oophorectomy in total (both
before and after study entry), 86.4% reported a high degree of
satisfaction with their decision to have the procedure. A low level of
screening uptake was also reported by women who did not have a
prophylactic oophorectomy but for whom screening was recommended.
CONCLUSION: Findings demonstrate that prophylactic oophorectomy is
successful in reducing anxiety about ovarian cancer. The results also
suggest that women perceive that the benefit of anxiety reduction may
outweigh the potentially adverse effects of the procedure, given that
women expressed a high level of satisfaction with their decision.
20
UI - 12151151
AU - Itamochi H; Kigawa J; Sugiyama T; Kikuchi Y; Suzuki M; Terakawa N
TI -
Low proliferation activity may be associated with chemoresistance in
clear cell carcinoma of the ovary.
SO - Obstet Gynecol 2002 Aug;100(2):281-7
AD - Department of Obstetrics and Gynecology, Tottori University, Yonago,
Japan.
OBJECTIVE: To estimate whether and how the biologic behavior of clear
cell carcinoma contributes to the chemoresistance mechanism. METHODS:
Forty-one patients with clear cell carcinoma and 90 patients with serous
adenocarcinoma, who had measurable disease after initial surgery, were
examined. All patients underwent cytoreductive surgery followed by
platinum-based chemotherapy. P-glycoprotein, multidrug
resistance-associated protein, and Ki-67 expression were determined by
immunohistochemical staining. RESULTS: The 5-year survival rate for
patients with clear cell carcinoma was significantly poorer, compared
with serous adenocarcinoma (20.0% versus 31.9%). Response rate to
chemotherapy was 14.6% for clear cell carcinoma and 72.2% for serous
adenocarcinoma. The expression of P-glycoprotein and multidrug
resistance-associated protein did not differ between responders and
nonresponders in both tumor types. The Ki-67 labeling index (LI) in
clear cell carcinoma was significantly lower than serous adenocarcinoma
(18.4% versus 38.8%). The LI for responders was significantly higher
than that for nonresponders in both tumor types. In clear cell
carcinoma, the mean value of LI was 15.3% for nonresponders, but that
for responders was 30.2%, which was similar to that for serous
adenocarcinoma. When the cutoff value of LI was set at 18.4% (mean
value), the 5-year survival rate for high LI (over 18.4%) patients was
significantly greater than that for low LI patients (46.3% versus 9.2%).
Multivariable analysis revealed that LI and residual tumor size were the
independent prognostic factors. CONCLUSION: Lower proliferation of tumor
may be a behavior of clear cell carcinoma of the ovary that contributes
to its resistance to chemotherapy.
21
UI - 12138243
AU - Itamochi H; Kigawa J; Akeshima R; Sato S; Kamazawa S; Takahashi M;
TI -
Kanamori Y; Suzuki M; Ohwada M; Terakawa N
Mechanisms of cisplatin resistance in clear cell carcinoma of the ovary.
SO - Oncology 2002;62(4):349-53
AD - Department of Obstetrics and Gynecology, Tottori University, Yonago,
Japan.
Resistance of clear cell carcinoma (CCC) of the ovary to platinum-based
chemotherapy is associated with a poor prognosis. However, the mechanism
underlying the resistance of CCC to platinum has not yet been
understood. We conducted the present study to clarify the mechanism of
cisplatin (CDDP) resistance in CCC cells. Eleven CCC and 5 serous
adenocarcinoma (SAC) cell lines were used in this study. The IC(50) to
CDDP ranged from 1.3 to 18.0 microM for CCC cells and from 2.2 to 13.0
microM for SAC cells. There was no correlation between multidrug
resistance-associated protein expression and the sensitivity to CDDP in
CCC cells. In contrast, the doubling time for CCC cells was
significantly longer than that for SAC cells (61.4 vs. 29.8 h). A
significant reverse correlation between the S-phase fraction and the
response to CDDP was observed (r = 0.647, p < 0.05). The present study
suggests that the resistance of CCC to CDDP may be caused by low cell
proliferation. Copyright 2002 S. Karger AG, Basel
22
UI - 12165628
AU - Liotta LA; Kohn EC
TI -
Stromal therapy: the next step in ovarian cancer treatment.
SO - J Natl Cancer Inst 2002 Aug 7;94(15):1113-4
23
25
26
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
UI - 12084463
AU - Jackman AL; Melin CJ; Kimbell R; Brunton L; Aherne GW; Theti DS; Walton
TI -
M
A rationale for the clinical development of the thymidylate synthase
inhibitor ZD9331 in ovarian and other solid tumours.
SO - Biochim Biophys Acta 2002 Jul 18;1587(2-3):215-23
AD - The Section of Medicine, Institute of Cancer Research, 15 Cotswold Road,
Belmont, Surrey, Sutton, UK. annj@icr.ac.uk
ZD9331 is an antifolate drug that potently and specifically inhibits
thymidylate synthase (TS). In contrast with TS inhibitors such as
raltitrexed, it cannot be polyglutamated, leading to antitumour activity
independent of folylpolyglutamyl synthetase (FPGS) activity.The growth
inhibition IC50 values for ZD9331 and raltitrexed were determined for a
panel of 18 human tumour cell lines, that included six colon and six
ovarian. The colon lines largely displayed overlapping sensitivities to
both drugs with only one of the six lines being drug resistant. In
contrast, the ovarian cell lines displayed non-overlapping sensitivities
with four being highly resistant to raltitrexed and only one was
cross-resistant to ZD9331. Studies were undertaken to explain these
results. The colon and ovarian cell lines were characterised for TS
activity, and TS and FPGS mRNA expression. TS activity correlated with
sensitivity to ZD9331 (r=0.50; p=0.097) and raltitrexed (r=0.74;
p=0.0063). Provided the data from the highly drug-resistant cell lines
(BE and 41 M) were omitted, TS mRNA expression levels also correlated
with ZD9331 (r=0.77; p=0.013) and raltitrexed IC50 (r=0.84; p=0.0031).
FPGS mRNA expression correlated with higher sensitivity to raltitrexed
relative to ZD9331 (higher ZD9331/raltitrexed IC50 ratios) (r=0.62;
p=0.048). Similarly, cell lines with IC50 ratios>median expressed a
1.8-fold higher median level of FPGS mRNA (p=0.0087) compared with those
with ratios
UI - 12183859
AU - Zidan J; Zohar S; Mijiritzky I; Kral S; Bilenca B
TI -
Treating relapsed epithelial ovarian cancer with luteinizing
hormone-releasing agonist (goserelin) after failure of chemotherapy.
SO - Isr Med Assoc J 2002 Aug;4(8):597-9
AD - Oncology Unit, Sieff Government Hospital, Safed, Israel.
zivsylvia@matat.health.gov.il
BACKGROUND: The treatment of patients with recurrent ovarian carcinoma
after failure of first and second-line chemotherapy is still debated.
Chemical agents used for third and fourth-line therapy usually yield
poor results with severe toxic side effects. OBJECTIVE: To summarize our
experience with goserelin in the treatment of patients with recurrent
administered goserelin, 3.6 mg subcutaneously every 4 weeks, to 15
patients with advanced and recurrent epithelial ovarian cancer (median
age 59.0, median performance status 3.0). RESULTS: Seven of 15 eligible
patients relapsed after platinum-based chemotherapy (3 of them also
received paclitaxel and another 2 received tamoxifen). Four patients
relapsed after carboplatin and paclitaxel, one of whom was treated with
topotecan thereafter. Two patients relapsed after single-agent
paclitaxel. Two patients with advanced disease and poor performance
status without previous treatment received only goserelin. There was one
complete response (6.7%) and 1 partial response (6.7%) lasting 8 and 14
months respectively (overall response rate 13.4%). In addition, the
disease stabilized in three patients (20%) for a median of 7.5 months.
In 10 patients the disease progressed. There was no significant
toxicity. Median survival of all patients was 5.8 months. CONCLUSION:
Goserelin was helpful in one-third of our patients with advanced and
refractory ovarian cancer. It is an easy and non-toxic option for
treating very ill or previously heavily treated patients.
UI - 12170444
AU - Hortobagyi GN; Kris MG
TI -
Expanding horizons: an update on the use of docetaxel in non-small cell
lung, ovarian, and breast cancers.
SO - Semin Oncol 2002 Jun;29(3 Suppl 12):1-3
AD - University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
UI - 12170448
AU - Kaye SB; Vasey PA
TI -
Docetaxel in ovarian cancer: phase III perspectives and future
development.
SO - Semin Oncol 2002 Jun;29(3 Suppl 12):22-7
AD - Cancer Research Campaign Department of Medical Oncology, The Royal
Marsden Hospital, Surrey, UK.
In the mid 1990s, the incorporation of paclitaxel into platinum-based
therapy for ovarian cancer marked a significant advance in treatment.
Future progress will probably involve reductions in toxicity, which may
be achieved by combining the less neurotoxic agent docetaxel with
carboplatin. In an international phase III study, 1,077
chemotherapy-naive patients with stage Ic-IV ovarian cancer were
randomized to receive carboplatin targeted to an AUC of 5 plus either
docetaxel 75 mg/m(2) or paclitaxel 75 mg/m(2) for six cycles. Patients
treated with paclitaxel plus carboplatin experienced significantly
greater neurotoxicity than those treated with docetaxel plus
carboplatin. Docetaxel/carboplatin and paclitaxel/carboplatin produced
similar rates of objective response (66% and 62%, respectively), and
initial data on progression-free survival indicate that the two
treatments appear very similar in efficacy. Thus, docetaxel may prove to
be a valid alternative to paclitaxel as part of first-line therapy in
ovarian cancer. Nevertheless, there remains considerable scope for
improvements in treatment. There is the possibility of using existing
drugs more effectively, perhaps by the use of sequential rather than
concurrent regimens. This would allow the most active drugs to be used
at full dose, increase tolerability, and avoid the possibility of
negative drug interaction. The integration of molecularly targeted
agents, such as those directed at epidermal growth factor receptors,
into existing regimens is highly promising but will need to be explored
in randomized trials of first-line therapy. Because the prime obstacle
to successful treatment is the acquisition of drug resistance,
understanding the underlying mechanisms is an important future priority.
One candidate is mismatch repair deficiency; the interest here is that
experimental resistance reversal is achievable with hypomethylating
agents, raising the possibility of future clinical trials if the
clinical relevance of this mechanism can be confirmed. Copyright 2002,
Elsevier Science (USA). All rights reserved.
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