National Cancer Institute®
Last Modified: August 1, 2002
1
UI - 11398912
AU - Curran M; Wiseman L
TI -
Fulvestrant.
SO - Drugs 2001;61(6):807-13; discussion 814
AD - Adis International Limited, Mairangi Bay, Auckland, New Zealand.
demail@adis.co.nz
Fulvestrant is a 7alpha-alkylsulphinyl analogue of estradiol that
competes with endogenous estrogen for binding to the estrogen receptor.
Once bound to the receptor, fulvestrant attenuates receptor
dimerisation, effecting a rapid degradation of the estrogen receptor
protein and inhibition of transcription. Fulvestrant is a potent
inhibitor of the growth of human breast cancer cells in vitro and in
vivo. It has demonstrated pure anti-estrogenic activity in animal
systems. Intramuscular fulvestrant 250 mg once a month was as effective
as the oral aromatase inhibitor anastrozole 1 mg/day in 2 phase III
trials in postmenopausal women with advanced breast cancer who had
received prior endocrine therapy. Median time to disease progression
(the primary end-point) with fulvestrant and anastrozole was 5.4 and 3.4
months (North American trial) and 5.5 and 5.1 months (European trial).
The median duration of response was 19.3 and 10.5 months (North American
trial) and 14.3 and 14.0 months (European trial). The most common
adverse events with fulvestrant are gastrointestinal disturbances and
hot flushes. Fulvestrant showed similar tolerability to anastrozole in 2
phase III trials.
2
UI - 11505951
AU - Longo F; Mansueto G
TI -
[Evolvement of hormone therapy for breast cancer. Florence, March 14,
2001]
SO - Tumori 2001 May-Jun;87(3):A6-14
AD - Oncologia Medica, Policlinico Umberto I, Roma.
3
UI - 12142395
AU - Schondorf T; Hoopmann M; Warm M; Neumann R; Thomas A; Gohring UJ;
TI -
Eisberg C; Mallmann P
Serologic concentrations of HER-2/neu in breast cancer patients with
visceral metastases receiving trastuzumab therapy predict the clinical
course.
SO - Clin Chem 2002 Aug;48(8):1360-2
AD - Department of Gynecology and Obstetrics, University of Cologne, Germany.
thomas.schoendorf@medizin.uni-koeln.de
4
UI - 12080536
AU - Lynn J
TI -
The oncology nurse's role in educating patients on endocrine therapy for
metastatic breast cancer--focus on fulvestrant.
SO - Cancer Nurs 2002 Apr;25 Suppl 2():12S-17S
AD - George Washington University Medical Center, Breast Care Center, 901
23rd St NW, Washington, DC 20037, USA.
Fulvestrant, an estrogen receptor downregulator, is an effective and a
safe endocrine option for postmenopausal women with advanced breast
cancer who progress or develop recurrent disease on prior endocrine
therapy. The recommended dose is 250 mg given as a single 5-mL or 2
concurrent 2.5-mL monthly intramuscular injections. Common adverse
events associated with fulvestrant are hot flashes, nausea, and mild
injection site reactions. Applying warm or cold compresses to the
injection site can minimize injection site reactions. In randomized
double-blind clinical trials, the frequency of injection site reactions
for fulvestrant are no different from the comparator (anastrozole) arm.
Overall, fulvestrant has a safety profile similar to aromatase
inhibitors. Advantages of this agent are its effectiveness in
tamoxifen-resistant tumors and the lack of agonistic property, creating
a favorable side-effect profile. One limitation is that there is no
evidence regarding the safety and effectiveness of fulvestrant in
premenopausal women. Among endocrine therapies used to treat breast
cancer, fulvestrant is unique not only in its mechanism of action but
also in its mode of administration. With oral therapies, the patient
fills the prescription in a pharmacy and takes the medication home. In
contrast, with monthly fulvestrant intramuscular injection, the patient
will have increased contact with the nurse. The increased interaction
between the patient and the nurse will affect the role of nurses
providing patient education and monitoring.
5
UI - 12080537
AU - Lynn J
TI -
Estrogen receptor downregulators: new advances in managing advanced
breast cancer.
SO - Cancer Nurs 2002 Apr;25 Suppl 2():2S-5S; quiz 18S-19S
AD - George Washington University Medical Center, Breast Care Center, 901
23rd St NW, Washington, DC 20037, USA.
Breast cancer is the most frequently diagnosed malignancy in American
women. Although potentially curable in the early stage, metastatic
breast cancer, however, is essentially incurable. Because metastatic
breast cancer is unlikely to be cured with currently available
therapies, the goals of treatment in this setting are prolonging
survival and maintaining or improving the quality of life. In patients
with receptor (estrogen or progesterone)-positive metastatic breast
cancer, endocrine therapy is generally considered the preferred
first-line therapy because of the superior tolerability and the similar
efficacy when compared with chemotherapy. Today a variety of endocrine
therapies are available for the treatment of metastatic breast cancer,
among which tamoxifen is the most widely used. Despite its proven
efficacy and safety, a significant proportion of patients do not respond
to tamoxifen. Further, due to its partial estrogenic activity, tamoxifen
is associated with an increased risk of thromboembolism and endometrial
cancer. Agents without any estrogenic activity-estrogen receptor
downregulators have therefore been developed. Fulvestrant is the first
clinically proven agent of this class. Oncology nurses have a key role
in managing and educating patients with breast cancer. This supplement
provides nurses with an overview of existing and emerging endocrine
therapies for postmenopausal patients with metastatic or advanced breast
cancer.
6
UI - 12080538
AU - Dow KH
TI -
Existing and emerging endocrine therapies for breast cancer.
SO - Cancer Nurs 2002 Apr;25 Suppl 2():6S-11S
AD - College of Health and Public Affairs, University of Central Florida, HPA
1 Suite 2210, Orlando, FL 32816-2210, USA.
Endocrine therapy is first-line therapy for patients with estrogen
receptor-positive or progesterone receptor-positive metastatic breast
cancer. Commonly used endocrine therapies are tamoxifen, megestrol
acetate, and aromatase inhibitors. Although tamoxifen and megestrol
acetate have a favorable therapeutic profile, there are risks associated
with these agents. With tamoxifen, the partial agonist property can lead
to thromboembolic events. An important adverse event of megestrol
acetate is weight gain and fluid retention in some patients. The
aromatase inhibitors are currently used as second-line therapy after
tamoxifen failure. A recent study showed that anastrozole, an aromatase
inhibitor, is as effective or even superior to tamoxifen when used as a
first-line therapy. However, not all patients will respond to currently
available therapies. A new class of drug, the estrogen receptor
downregulators, has been developed. Fulvestrant, the first agent in this
new class, not only induces the degradation of the estrogen receptor but
also is an estrogen antagonist; further, its lack of agonist activity
provides a better safety profile. Two phase III trials have proven that
fulvestrant is at least as effective as anastrozole in postmenopausal
women with advanced breast cancer. Fulvestrant is an effective and safe
endocrine therapy for postmenopausal women who have failed prior
endocrine therapy.
7
UI - 12113239
AU - Nabholtz JM; Reese DM; Lindsay MA; Riva A
TI -
Combination chemotherapy for metastatic breast cancer.
SO - Expert Rev Anticancer Ther 2002 Apr;2(2):169-80
AD - University of California, Los Angeles, Peter Ueberroth Building 3360B,
10945 Le Conte Avenue, Los Angeles, CA 90095-7077, USA.
jean-marc.nabholtz@bcirg.com
Despite more than four decades of effort, the improvement in survival in
metastatic breast cancer has been modest. Recently, however, new drugs
such as the taxanes have emerged as pivotal agents in the treatment of
metastatic disease and they are now being investigated in the adjuvant
setting. In addition, the introduction of molecularly targeted therapies
such as trastuzumab provides a new paradigm for the development of
biologic treatments. The incorporation of trastuzumab into new
combination regimens based on potential molecular synergies is a focus
of current research.
8
UI - 12116603
AU - Russell CA
TI -
Adjuvant systemic therapy for lymph node-negative breast cancer less
than or equal to 1 cm.
SO - Curr Womens Health Rep 2002 Apr;2(2):134-9
AD - Department of Medicine-Oncology, Keck School of Medicine, University of
Southern California, NOR 3448, MC 9173, Los Angeles, CA 90089, USA.
carussel@hsc.usc.edu
Routine screening mammography has increased the incidence of stage I
breast cancers. Many more women are being diagnosed with lymph
node-negative tumors that are less than or equal to 1 cm in greatest
diameter. The National Surgical Adjuvant Breast and Bowel Project
recently performed a retrospective analysis of 10,302 women
participating in one of five clinical trials, including women with lymph
node-negative breast cancer. Of these women, 1259 had tumors less than
or equal to 1 cm. The analysis of the women with tumors less than or
equal to 1 cm revealed an improved relapse-free survival (RFS) if
tamoxifen was given after surgery, compared with surgery alone, for
women with estrogen receptor (ER)-positive tumors; and for women with
ER-negative tumors, RFS was improved by delivering chemotherapy after
surgery. The authors suggested that adjuvant systemic therapy should be
considered for anyone with an invasive breast cancer, regardless of the
size of the tumor. This paper reviews the data presented in that
important, historic article, and discusses their conclusions. Also
reviewed are the most recent recommendations for treatment of primary
breast cancer from the International Consensus Panel that convened at
the Seventh International Conference on Adjuvant Therapy of Primary
Breast Cancer in St. Gallen, Switzerland. That panel also addressed the
issue of adjuvant systemic therapy in women considered to have a minimal
or low risk of developing recurrent disease.
9
UI - 12109640
AU - Hill J; Moore H
TI -
Aromatase inhibitors in breast cancer: current and evolving roles.
SO - Cleve Clin J Med 2002 Jul;69(7):561-7
AD - Department of Hematology and Medical Oncology, The Cleveland Clinic
Foundation, OH 44195, USA.
The aromatase inhibitors are established first-line drugs for treating
metastatic breast cancer in postmenopausal women, and are gaining
acceptance as adjuvant treatment as well.
10
UI - 12122089
AU - Wolff AC; Abeloff MD
TI -
Adjuvant chemotherapy for postmenopausal lymph node-negative breast
cancer: it ain't necessarily so.
SO - J Natl Cancer Inst 2002 Jul 17;94(14):1041-3
11
UI - 12118024
AU - Osoba D; Slamon DJ; Burchmore M; Murphy M
TI -
Effects on quality of life of combined trastuzumab and chemotherapy in
women with metastatic breast cancer.
SO - J Clin Oncol 2002 Jul 15;20(14):3106-13
AD - Quality of Life Consulting, West Vancouver, British Columbia, Canada.
david_osoba@telus.net
PURPOSE: The study was designed to compare the effects of treatment with
a combination of trastuzumab (Herceptin; Genentech, Inc, South San
Francisco, CA) and chemotherapy versus chemotherapy alone on
health-related quality of life (HRQL) in patients with HER-2/neu
overexpressing, metastatic breast cancer. PATIENTS AND METHODS: A sample
of 400 patients, not previously treated for metastatic disease and
randomized to receive either trastuzumab plus chemotherapy (208
patients) or chemotherapy alone (192 patients), completed the European
Organization for Research and Treatment Care Quality of Life
Questionnaire at baseline and on at least one subsequent occasion at 8,
20, 32, 44, and 56 weeks. HRQL improvement or worsening was defined as a
>or= 10-point change (range, 0 to 100 points) in the scores of six
preselected domains (global quality of life [QOL], physical, role,
social, and emotional functioning, and fatigue). Stable HRQL was defined
as a change of less than 10. A Bonferroni correction was applied for
multiple testing. RESULTS: After completion of chemotherapy, patients
treated with trastuzumab and chemotherapy reported significant
improvement in fatigue (P <.05) as compared with their baseline scores.
Higher proportions of patients receiving the combined therapy achieved
improvement in global QOL (P <.05) than did patients treated with
chemotherapy alone. Higher proportions of the combined therapy group
also achieved improvement in physical and role functioning and in
fatigue as compared with the chemotherapy group, but the differences
were not statistically significant. There were no differences in the
proportions of patients in the two groups that reported worsening.
CONCLUSION: Statistically significantly higher proportions of patients
treated with a combination of trastuzumab and chemotherapy reported
improved global QOL than did patients treated by chemotherapy alone.
12
UI - 12118025
AU - Biganzoli L; Cufer T; Bruning P; Coleman R; Duchateau L; Calvert AH;
TI -
Gamucci T; Twelves C; Fargeot P; Epelbaum R; Lohrisch C; Piccart MJ
Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as
first-line chemotherapy in metastatic breast cancer: The European
Organization for Research and Treatment of Cancer 10961 Multicenter
Phase III Trial.
SO - J Clin Oncol 2002 Jul 15;20(14):3114-21
AD - Investigational Drug Branch for Breast Cancer, European Organization for
the Research and Treatment of Cancer Data Center, and Jules Bordet
Institute, Brussels, Belgium.
PURPOSE: To compare the efficacy and tolerability of the combination of
doxorubicin and paclitaxel (AT) with a standard doxorubicin and
cyclophosphamide (AC) regimen as first-line chemotherapy for metastatic
breast cancer. PATIENTS AND METHODS: Eligible patients were
anthracycline-naive and had bidimensionally measurable metastatic breast
cancer. Two hundred seventy-five patients were randomly assigned to be
treated with AT (doxorubicin 60 mg/m(2) as an intravenous bolus plus
paclitaxel 175 mg/m(2) as a 3-hour infusion) or AC (doxorubicin 60
mg/m(2) plus cyclophosphamide 600 mg/m(2)) every 3 weeks for a maximum
of six cycles. A paclitaxel (200 mg/m(2)) and cyclophosphamide (750
mg/m(2)) dose escalation was planned at cycle 2 if no grade >or= 3
neutropenia occurred in cycle 1. The primary efficacy end point was
progression-free survival (PFS). Secondary end points were response rate
(RR), safety, overall survival (OS), and quality of life. RESULTS: A
median number of six cycles were delivered in the two treatment arms.
The relative dose-intensity and delivered cumulative dose of doxorubicin
were lower in the AT arm. Dose escalation was only possible in 17% and
20% of the AT and AC patients, respectively. Median PFS was 6 months in
the two treatments arms. RR was 58% versus 54%, and median OS was 20.6
versus 20.5 months in the AT and AC arms, respectively. The AT regimen
was characterized by a higher incidence of febrile neutropenia, 32%
versus 9% in the AC arm. CONCLUSION: No differences in the efficacy
study end points were observed between the two treatment arms.
Treatment-related toxicity compromised doxorubicin-delivered
dose-intensity in the paclitaxel-based regimen
13
UI - 12124820
AU - Cocconi G; Di Blasio B; Boni C; Bisagni G; Ceci G; Rondini E; Bella M;
TI -
Leonardi F; Savoldi L; Camisa R; Bruzzi P
Randomized trial comparing cyclophosphamide, methotrexate, and
5-fluorouracil (CMF) with rotational CMF, epirubicin and vincristine as
primary chemotherapy in operable breast carcinoma.
SO - Cancer 2002 Jul 15;95(2):228-35
AD - Medical Oncology Division, Azienda Ospedaliera Universitaria, Parma,
Italy. giorgio.cocconi@tin.it
BACKGROUND: According to the overview of Early Breast Cancer Trialists'
Collaborative Group, anthracycline containing regimens are superior to
cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) as adjuvant
chemotherapy for breast carcinoma, but no comparative information is
available in terms of primary chemotherapy. In the current randomized
controlled trial, the authors compared CMF with a chemotherapy regimen
including CMF, epirubicin, and vincristine (CMFEV). METHODS: Two hundred
eleven patients with Stages I and II palpable breast carcinoma and tumor
diameter > 2.5 cm or < or = 2.5 cm with cytologically proven axillary
lymph node involvement were randomized to receive CMF (arm A) or CMFEV
regimen (arm B) for four cycles before surgery. After surgery, patients
in both arms received adjuvant CMF for three cycles; the postmenopausal
patients also received tamoxifen for two years. RESULTS: There were no
significant differences in the complete response (CR) and in the CR plus
partial response (PR) rates between the two arms. In the subset
analysis, among premenopausal patients, significantly higher rates of CR
(26% vs 4%, P = 0.004) and of CR + PR rates (80% vs 54%, P = 0.007) were
observed in the CMFEV, as compared to the CMF arm. Multivariate analysis
confirmed the presence of a significant interaction between menopausal
status and type of treatment on the probability of achieving CR (P =
0.02) or CR + PR (P = 0.01). There were no major differences in the side
effects of the two treatments, with the exception of more frequent
alopecia in the experimental arm. CONCLUSIONS: The results of the
current study are in line with those of previous published randomized
clinical trials comparing regimens without and with anthracycline as
adjuvant treatment, indicating an agreement between the short term
response to primary chemotherapy and the long term results observed in
the adjuvant setting. Copyright 2002 American Cancer Society.DOI
10.1002/cncr.10678
14
UI - 11843244
AU - Depierre A; Freyer G; Jassem J; Orfeuvre H; Ramlau R; Lemarie E;
TI -
Koralewski P; Mauriac L; Breton JL; Delozier T; Trillet-Lenoir V
Oral vinorelbine: feasibility and safety profile.
SO - Ann Oncol 2001 Dec;12(12):1677-81
AD - Department of Pneumology, Centre Hospitalier Universitaire Minjoz,
Besancon, France.
BACKGROUND: Patient preference as well as concerns and difficulties with
intravenous access and pharmaco-economic issues have driven the
development of oral vinorelbine. PATIENTS AND METHODS: Four phase II
studies were conducted in chemotherapy-naive non-small-cell lung cancer
(NSCLC) and as first-line chemotherapy of advanced breast cancer (ABC).
As recommended in the phase I dose-finding study, the first step used a
weekly dose of 80 mg/m2. This regimen was associated with an excessive
rate of early deaths (10%) due to complicated neutropenia and led to
discontinuation of the first two studies. In a second step, the dose of
60 mg/m2/week was given for the first three courses and subsequently
increased to 80 mg/m2/week, in the absence of severe neutropenia.
RESULTS: One hundred and thirty eight patients (76 with NSCLC and 62
with ABC) received this regimen, of whom only five were unable to
undergo dose escalation. The incidence of febrile neutropenia and
neutropenic sepsis were low (2.9 and 3.6%, respectively). Although
severe events were uncommon, nausea/vomiting and diarrhoea were frequent
and primary prophylaxis with antiemetics should be recommended.
CONCLUSIONS: Overall, the safety profile of oral vinorelbine at 60
mg/m2/week for the first three courses with escalation to 80 mg/m2 is
qualitatively comparable to that of i.v. vinorelbine at standard doses.
Similarly to i.v. chemotherapy, close haematological monitoring is
necessary.
15
UI - 12029440
AU - Otto AM; Muller CS; Huff T; Hannappel E
TI -
Chemotherapeutic drugs change actin skeleton organization and the
expression of beta-thymosins in human breast cancer cells.
SO - J Cancer Res Clin Oncol 2002 May;128(5):247-56
AD - Institute of Biochemistry University of Nuremberg-Erlangen, Fahrstr. 17,
91054 Erlangen, Germany. angela.otto@ei.tum.de
PURPOSE: Elevated expression of the beta-thymosin isotypes T beta(4), T
beta(10), and T(15) appears to be involved in the manifestation of a
malignant phenotype of human tumor cells, including those of mammary
carcinomas. This has evoked an interest in these peptides as
diagnostic/prognostic tumor markers. If increased levels of
beta-thymosins correspond to tumor malignancy, the question arises
whether tumor growth inhibition induced by chemotherapeutic drugs would
reduce their expression. METHODS: Two human breast cancer cell lines,
the estrogen receptor(ER)-positive MCF-7 and the ER-negative MDA-MB231,
were thus analyzed for the amount of beta-thymosin mRNAs by RNase
protection assay and for the respective peptide levels by HPLC following
different hormonal and drug treatments. RESULTS: Both cell lines,
growing in medium with 10% FCS, contain T beta(4) (400-500 fg/cell) and
Tbeta(10) (about 100 fg/cell), but no T beta(15). Incubating MCF-7 cells
with tamoxifen (1 microM) for 5 days resulted in about 80% growth
inhibition and in reduction of intracellular T beta(4) and T beta(10)
concentrations by about 40%. Levels of T beta(4) and T beta(10)-mRNA
were reduced by about 60%. In contrast, cisplatin (2 microM) changed
neither the peptide concentrations nor the mRNA levels of
beta-thymosins, in spite of marked growth inhibition. In addition, no
changes in beta-thymosin expression were observed in MDA-MB231 cells
treated with either drug. MCF-7 cells maintained in estrogen-poor medium
(10% horse serum) or stimulated to grow with estradiol (1 nM) had
Tbeta(4) and T beta(10) concentrations reduced by about 30%, but changes
in T beta(4)- and T beta(10)-mRNA levels did not correspond to those of
the peptide. CONCLUSION: Expression of T beta(4) and T beta(10) mRNAs
and their peptides is differentially regulated and does not correlate
with growth. Instead, reduced beta-thymosin expression may be linked to
more intensive TRITC-phalloidin staining of F-actin lining the membrane
at sites of intimate cell-cell contacts, while increased beta-thymosin
levels appear in cells with more extensive substrate adhesion. This
suggests that beta-thymosins play a role in cell surface dynamics.
16
UI - 12082808
AU - Dimitrievich E; Sterzinger A
TI -
Dual breast cancers followed by endometrial cancer.
SO - S D J Med 2002 Jun;55(6):227-9
AD - USD School of Medicine, Sioux Falls, USA.
Two cases in which dual breast cancers occurred at several years
interval, followed by endometrial cancer are described. The risk factors
for dual breast cancers, the association between breast and endometrial
cancer, and the association of tamoxifen therapy with endometrial
cancer, and future cancer risk will be briefly discussed.
17
UI - 12145989
AU - Inaji H; Komoike Y; Motomura K; Kasugai T; Koyama H
TI -
[The role of neoadjuvant chemotherapy for breast cancer treatment]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1113-9
AD - Dept. of Surgery III, Osaka Medical Center for Cancer and Cardiovascular
Diseases.
Neoadjuvant chemotherapy is being used increasingly in the management of
patients with breast cancer, especially locally advanced cases. Such
treatment is administered with the aim of of reducing the size of the
primary tumor to increase the possibility of breast-conserving treatment
86 patients with tumors between 3.1 and 6.0 cm in diameter received
epirubicin-based neoadjuvant chemotherapy. There were 55 (64.0%)
responders and ultimately 64 patients (74.4%) were treated with BCT.
With a median follow-up time of 39 months, 9 patients in the BCT group
had developed local recurrence. Long-term follow-up is required to
establish whether this procedure is a safe alternative to mastectomy for
patients with large breast cancers.
18
UI - 12145993
AU - Matsui A; Ikeda T; Jinno H; Tajima G; Hohjou T; Tokura H; Mitsui Y;
TI -
Asaga S; Muto T; Kitajima M
[Developments in endocrine therapy for breast cancer]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1138-45
AD - Keio Cancer Center, Keio University Hospital.
After the usefulness of ovariectomy in breast cancer patients was
demonstrated, endocrine therapy has been one of the most effective
treatments of breast cancer. Thereafter, it became clear that estrogen
receptors (ERs) existed in the cells of breast cancer. After it was
found that ERs could be used as a predictive factor of endocrine therapy
for breast cancer, the validity of endocrine therapy has became more
certain. Tamoxifen, a major selective estrogen receptor modulator, is
the first agent which has shown evidence of improving survival time and
disease-free survival time in the treatment of breast cancer, and is the
standard treatment, widely used in the treatment of breast cancer all
over the world. LH-RH analogue, commonly used in ablation treatment
among premenopausal women, produces the same effect as ovariectomy, and
recently has shown good results equivalent to chemotherapy in
premenopausal breast cancer treatment. Furthermore, aromatase inhibitors
as a form of ablation treatment of postmenopausal women have been used
recently. In comparison with tamoxifen, aromatase inhibitors have
revealed the same or more effective result in postmenopausal breast
cancer treatment. In the near future, endocrine mechanisms in the body
and the molecular mechanisms of transcription by ER will be more clearly
elucidated, and then new kinds of agent and combined therapies for the
endocrine treatment of breast cancer will be developed. Currently, many
clinical randomized trials are being conducted to examine the
effectiveness of new endocrine treatment. Significant changes are
occurring in the endocrine treatment of breast cancer.
19
UI - 12145994
AU - Tong F; Zhou B; Yang D; Cao Y; Liu P; Liu H; Qiao X; Zhang J
TI -
[Clinical evaluation of effects from neo-adjuvant chemotherapy with
epirubicin plus paclitaxel in cases of locally advanced breast cancer]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1147-52
AD - Dept. of 4th Surgery and Breast Disease Research Center, People's
Hospital, Beijing University Medical School.
Neo-adjuvant chemotherapy of epirubicin plus paclitaxel was administered
to 23 patients with locally advanced breast cancer (including 13 cases
of stage IIb, 6 of stage IIIa, and 4 of stage IIIb). All patients were
female. They were treated with epirubicin 60 mg/m2, on day 1, by i.v.
followed paclitaxel 150 mg/m2 by 3 hours continuous infusion on day 2
and every 3 weeks repeatedly. Premedication with dexamethasone,
ondansetron, diphenhydramine and cimetidine were administered to prevent
gastroenteric and allergic reactions before chemotherapy. Two to 4
cycles were used. Ten out of 23 patients had a complete response, 10 had
partial response, and 3 had no change. The response rate was 87%
(20/23). Six out of 23 patients underwent breast conserving surgery as
tumor size had become smaller and downstaging was realized after
neo-adjuvant chemotherapy. The major toxicities included neutropenia,
myalgia, arthralgia, nephrotoxicity, gastroenteric reactions, alopecia
and flushing to the face. However, these were well tolerated in these
patients.
20
UI - 12145999
AU - Miura S; Tominaga T; Koyama H; Nomura Y; Tsuboi M
TI -
[Phase I single-dose administration study of exemestane in
postmenopausal women]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1179-87
AD - Aichi Cancer Center Hospital.
A single-dose administration study of a new type of aromatase
inactivator, exemestane, was performed in normal healthy postmenopausal
Japanese women. The study was conducted to investigate the safety,
effect on serum and urinary estrogen concentrations, and
pharmacokinetics of exemestane at 25 or 50 mg. A crossover study using a
single dose (25 mg) was also conducted in order to study the effect of
meals on these parameters. Adverse events, in which a causal
relationship with the study drug could not be excluded, were as follows:
hot flushes (2/4), sleepiness (1/4), and glycogeusia (1/4), all of which
were mild and transient. There were no clinically significant laboratory
test or physical finding abnormalities with either dose, except for one
patient in the 50 mg group who had an increase in levels of GPT, ALP and
gamma-GTP. Maximal suppression of serum estrogen concentration (22-37%
suppression) was achieved 3-4 days after single-dose administration of
exemestane (25 mg or 50 mg), and almost no suppression was observed 2
weeks later. A significant decrease in the amount of urinary estrogen
excretion occurred on day 4 and day 8 after exemestane administration.
The level of urinary estrogen excretion almost returned to baseline
levels in the 25 mg group and returned to 65% of baseline levels in the
50 mg group 2 weeks after drug administration. Both serum estrogen
concentration and the amount of urinary estrogen excreted decreased in a
similar fashion under both fasting and fed conditions, suggesting no
effect of meals on the suppression of estrogen concentrations.
Exemestane was adsorbed immediately after single-dose administration,
and this was followed by a gradual decrease in serum concentrations in a
multiphase pattern. An increase in Cmax and AUC0-tz values was observed
after meals compared with those values obtained under fasting
conditions, yet the increase was not statistically significant,
suggesting that the increase was not clinically relevant. The results of
this study verified the safety and the estrogen suppressive effects on
serum and urinary concentrations of estrogen of a single dose of
exemestane up to 50 mg. Furthermore, results suggest that the
suppression of serum and urinary estrogen concentrations and
pharmacokinetics of exemestane were not affected by food.
21
UI - 12146001
AU - Tabei T; Ogita M; Hirata K; Satomi S; Kimura M; Abe R; Morishita Y;
TI -
Kimura M; Andou J; Higashi Y; Yoshino K; Tominaga K; Kajiwara T;
Kitajima M; Koyanagi Y; Watanabe T; Yamaguchi S; Watanabe M; Toyama K;
Kanda K; Kashiki Y; Miura S; Kobayashi Z; Aoyama H; Miyazaki I; Oka T;
Koyama H; Kinoshita H; Monden M; Takai S; Yayoi E; Kobayashi T;
Takatsuka Y; Kajiwara T; Sonoo H; Toge T; Takashima S; Nomura Y; Nagao
K; Fujita Y
[Early phase II dose-finding study of exemestane in postmenopausal
patients with advanced/recurrent breast cancer]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1199-209
AD - Saitama Cancer Center.
Exemestane was administered orally to postmenopausal women with
advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day
once daily for more than 8 weeks in order to evaluate the drug's
anti-tumor effects and safety in a dose-finding study. The response rate
(CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4%
(11/35), respectively, demonstrating no significant differences between
the two groups, yet a higher efficacy rate was observed in 25 mg group.
The efficacy rate in hormone-treatment-resistant patients within the 10
mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively,
demonstrating more than a 20% response rate in 25 mg group. Incidences
of the adverse events of which relevance to the drug could not be
excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25
mg group and 22.2% (16/72) in the total group. The major adverse events
were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal
findings in clinical laboratory tests were as follows: ALP increase; GOT
increase; GPT increase; gamma-GTP increase; total cholesterol increase;
urinary sediment present. Abnormal findings in endocrine function were
as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease.
But discontinuation due to abnormal laboratory findings was not found.
No abnormal findings in physical tests were observed. A significant
decrease in plasma estrogen concentration at week 4 was observed in both
the 10 mg and 25 mg groups compared with baseline. These low levels were
maintained throughout the study period. On the basis of these results,
the efficacy of exemestane 25 mg/day was verified to be slightly higher
than 10 mg/day. In addition the safety profile had no major adverse
events to notice. In these patients with advanced/recurrent breast
cancer, 25 mg/day was recommended as the most appropriate dose to be
used clinically.
22
UI - 12146002
AU - Watanabe T; Sano M; Toi M; Saeki T; Kanda K; Miura S; Inaji H; Sono H;
TI -
Saeki H; Nishimura R; Fujita Y
[Late phase II study of exemestane in postmenopausal patients with
breast cancer resistant to anti-estrogenic agents]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1211-21
AD - Division of Internal Medicine, National Cancer Center Hospital.
A multi-center trial of exemestane 25 mg, an oral aromatase irreversible
inactivator, was conducted to evaluate its efficacy and safety in 33
postmenopausal patients, and to investigate the pharmacokinetics/serum
hormone levels in 16 postmenopausal patients, respectively, with breast
cancer and anti-estrogen resistance. Exemestane 25 mg was given once
daily for up to 48 weeks (maximum). The objective of this study was to
confirm the reproducibility of the results shown in two studies in other
countries with similar patients, to investigate the possibility of
extrapolating the overseas data to Japanese. The response rate (CR + PR)
was 24.2% (8.33%), which exceeded the minimum number (6 cases) required
to evaluate efficacy. The response rate in this study was very similar
to that observed in the two international open studies. Adverse events
(subjective/objective symptoms), in which a causal relationship with
exemestane administration could not be excluded, were observed in 26
cases (78.8%). Of these, hot flushes, increased sweating, fatigue, and
insomnia occurred in more than 10% of patients, which was similar to
that observed in the two international open studies. Abnormal laboratory
results occurring in more than 10% of patients, in which a causal
relationship with exemestane administration could not be excluded, were
as follows: lymphocyte count decrease, alkaline phosphate increase, GOT
increase, GPT increase, gamma-GTP increase, triglyceride increase, and
inorganic phosphate increase, most of which were either grade 1 or 2. A
remarkable decrease in serum hormone concentration was observed only for
estrogen. The values of AUC0-infinity at day 1 and AUC0-24 h at day 29
(steady state) were similar, suggesting no accumulative effect of
exemestane. These results demonstrate the anti-tumor effect and safety
of exemestane in postmenopausal anti-estrogen resistant breast cancer
patients. The reproducibility of the results of the two foreign studies
was verified in Japanese patients, and it is concluded that the foreign
trial data on exemestane can be extrapolated to Japanese.
23
UI - 12146005
AU - Harada T; Hara A; Tsunematsu I; Matsubara C; Izumi N; Iwamoto S; Satake
TI -
K
[One case of locally advanced breast cancer in which multidisciplinary
treatment, chiefly, therapy with preoperative intraarterial infusion of
docetaxel (TXT), was successful]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1231-4
AD - Dept. of Digestive/General Surgery, Saiseikai-Affiliated Suita Hospital.
We herein report 1 case in which hormone therapy and neoadjuvant
chemotherapy by local intraarterial infusion were conducted for locally
advanced breast cancer, and were revealed to be useful in terms of local
control. Administration of doxifluridine (5'-DFUR: Furtulon) (1,200
mg/day, 5 day continuous dosing followed by 2 day washout) and
medroxyprogesterone acetate (MPA: Hysron H) (1,200 mg/day) was followed
by chemotherapy consisting of intraarterial infusion of 100 mg of
docetaxel (TXT: Taxotere), once monthly, via the left internal thoracic
artery and left lateral thoracic artery. As a result, marked shrinkage
of tumors was confirmed. Under these circumstances, left standard
radical mastectomy plus skin grafting were performed. While under
treatment, no serious adverse events were observed, and the patient made
satisfactory progress after surgical procedure. She thus left hospital
in a positive frame of mind.
24
UI - 11911507
AU - Jordan C
TI -
Historical perspective on hormonal therapy of advanced breast cancer.
SO - Clin Ther 2002;24 Suppl A():A3-16
AD - Robert H. Lurie Comprehensive Cancer Center, Northwestern University
School of Medicine, Chicago, Illinois 60611, USA.
BACKGROUND: Endocrine therapy is the preferred first-line therapy in
patients with nonaggressive, receptor-positive, metastatic breast
cancer. Endocrine therapies in these patients are as effective as
chemotherapy in terms of survival and tumor response. In addition,
hormonal therapies produce fewer and less severe adverse effects than
does chemotherapy. Classes of endocrine therapy currently on the market
include selective estrogen receptor modulators (SERMs), aromatase
inhibitors, and progestins. For several decades, tamoxifen has been
considered the gold standard of therapy. However, despite its proven
efficacy, a high proportion of patients do not respond. Therefore, a
need exists for alternative therapies or for agents to use following
tamoxifen failure. OBJECTIVE: This review article highlights the various
endocrine options available for patients with advanced breast cancer and
discusses new agents on the horizon. CONCLUSIONS: Although more studies
are needed to determine the optimal sequence of hormonal therapy and the
ideal agent within each class, the availability of new and multiple
options is encouraging for women with advanced breast cancer.
25
UI - 11911508
AU - Torosian M; O'Shaughnessy J; Parker LM; Vogel C
TI -
Fulvestrant: clinical application of an estrogen receptor downregulator.
SO - Clin Ther 2002;24 Suppl A():A31-40
AD - Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
joyce.oshaughnessy@usoncology.com
26
UI - 11948114
AU - Coon JS; Marcus E; Gupta-Burt S; Seelig S; Jacobson K; Chen S; Renta V;
TI -
Fronda G; Preisler HD
Amplification and overexpression of topoisomerase IIalpha predict
response to anthracycline-based therapy in locally advanced breast
cancer.
SO - Clin Cancer Res 2002 Apr;8(4):1061-7
AD - Rush Medical College, Chicago, Illinois 60612, USA. jcoon@rush.edu
PURPOSE: The putative association between erbB-2 overexpression and
favorable response to anthracyline-based therapy in breast cancer is
controversial, and the mechanism unclear. We sought to determine whether
coamplification and overexpression of the topoisomerase IIalpha gene,
near erbB-2 on chromosome 17, and a known anthracycline target, may
underlie the association. EXPERIMENTAL DESIGN: Thirty-five patients who
had locally advanced breast cancer (LABC) and who had received
neoadjuvant, anthracycline-based therapy were studied. Copy number of
topoisomerase IIalpha and erbB-2 was determined by fluorescence in situ
hybridization, and expression by immunohistochemistry. RESULTS: Of 8
patients with erbB-2 amplification, 5 had a complete response (CR) or
minimal residual disease (MRD), 3 had a partial response (PR), and none
had stable (StD) or progressive disease (PD) at the time of mastectomy,
versus 3 CR or MRD, 16 PR, and 8 StD or PD for patients without
amplification (P = 0.008). In contrast, erbB-2 overexpression was not
significantly associated with response (P = 0.114). Of 6 patients with
topoisomerase IIalpha amplification, 4 had CR or MRD, 2 PR, and none StD
or PD, versus 4 CR or MRD, 17 PR, and 8 StD or PD for patients without
amplification (P = 0.034). All of the tumors with topoisomerase IIalpha
amplification also had erbB-2 amplification, but not vice versa.
Overexpression of topoisomerase IIalpha (9 patients) was also associated
with favorable response (P = 0.021). CONCLUSIONS: Coamplification of
erbB-2 and topoisomerase IIalpha is significantly associated with
favorable local response to anthracycline-based therapy in LABC. The
expression data favor a plausible mechanism based on topoisomerase
IIalpha biology.
27
UI - 12063069
AU - Holy JM
TI -
Curcumin disrupts mitotic spindle structure and induces micronucleation
in MCF-7 breast cancer cells.
SO - Mutat Res 2002 Jun 27;518(1):71-84
AD - Department of Anatomy and Cell Biology, UMD School of Medicine, 10
University Drive, Duluth, MN 55812-2487, USA. jholy@d.umn.edu
The dietary phytochemical curcumin possesses anti-inflammatory,
-oxidant, and cytostatic properties, and exhibits significant potential
as a chemopreventative agent in humans. Although many cell types are
arrested in the G2/M-phase of the cell cycle after curcumin treatment,
the mechanisms by which this occurs are not well understood. The purpose
of this study was to examine the effects of curcumin on the cell cycle
of MCF-7 breast cancer cells to determine whether growth arrest is
associated with structural changes in cellular organization during
mitosis. For this purpose, MCF-7 breast cancer cells were treated with
10-20 microM curcumin, and the effects on cell proliferation and mitosis
studied. Structural changes were monitored by immunolabeling cells with
antibodies to a number of cytoplasmic and nuclear proteins, including
beta-tubulin, NuMA, lamins A/C and B1, lamin B receptor, and centromere
antigens. At the concentrations used, a single dose of curcumin does not
induce significant apoptosis, but is highly effective in inhibiting cell
proliferation for over 6 days. During the first 24-48 h of treatment,
many cells are arrested in M-phase, and DNA synthesis is almost
completely inhibited. Remarkably, arrested mitotic cells exhibit
monopolar spindles, and chromosomes do not undergo normal anaphase
movements. After 48 h, most cells eventually leave M-phase, and many
form multiple micronuclei instead of individual daughter nuclei. These
observations indicate that the curcumin-induced G2/M arrest previously
described for MCF-7 cells is due to the assembly of aberrant, monopolar
mitotic spindles that are impaired in their ability to segregate
chromosomes. The production of cells with extensive micronucleation
after curcumin treatment suggests that at least some of the cytostatic
effects of this phytochemical are due to its ability to disrupt normal
mitosis, and raises the possibility that curcumin may promote genetic
instability under some circumstances.
28
UI - 12113022
AU - Koberle D; Thurlimann B
TI -
Anastrozole: pharmacological and clinical profile in postmenopausal
women with breast cancer.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):169-76
AD - Department of Oncology and Hematology, Kantonsspital St. Gallen,
Switzerland.
A significant proportion of breast cancers are estrogen-dependent and
are therefore amenable to endocrine therapy. Although tamoxifen has been
the mainstream of endocrine treatment for over 20 years, new agents have
entered the clinic, which have potentially superior activity and an
improved safety profile. The development of orally-active, potent and
selective third-line aromatase inhibitors represents a major advantage
in the management of hormone-sensitive breast cancer. Anastrozole
(Arimidex) was the first of these agents to become available and is
currently widely indicated for both first- and second-line treatment for
postmenopausal women with breast cancer. This review focuses on the
biochemical properties and clinical efficacy of anastrozole, providing
an overview of the current clinical status and possible future
applications.
29
UI - 12113005
AU - Swords EP
TI -
Breast cancer response.
SO - Am J Nurs 2001 Aug;101(8):13; discussion 13-4
30
UI - 12107551
AU - Asai G; Yamamoto N; Toi M; Shin E; Nishiyama K; Sekine T; Nomura Y;
TI -
Ta