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Abramson Cancer CenterNCI CANCERLIT® Search: Chemotherapy for Breast Cancer - March 2002
National Cancer Institute®
Last Modified: March 1, 2002
Table of Contents
1
UI - 11753438
AU - Czeczuga-Semeniuk E; Wolczynski S; Dzieciol J; Dabrowska M; Anchim T;
TI -
Tomaszewska I
13-cis retinoic acid and all-trans retinoic acid in the regulation of
the proliferation and survival of human breast cancer cell line MCF-7.
SO - Cell Mol Biol Lett 2001;6(4):925-39
AD - Department of Gynaecological Endocrinology, Medical Academy of
Bialystok, 15-276 Bialystok, M. Sklodowskiej-Curie 24 A, Poland.
Retinoids are a group of compounds which inhibit cell proliferation and
induce cellular differentiation. The aim of this study was to compare
the antiproliferative activity of various concentrations of 13-cis
retinoic acid (isotretinoin) and all-trans retinoic acid (tretinoin) in
a culture of the estrogen-sensitive human breast cancer cell line MCF-7.
Evaluation was based on [3H]thymidine incorporation into the cancer
cells and through immunocytochemical analysis of cell cycle-associated
PCNA and Ki-67 protein expression. Both retinoids inhibited
[3H]thymidine incorporation into the cancer cells most effectively at a
concentration of 3x10(-3) M. Two basic substances used for line MCF-7
culture experiments, one stimulating - estradiol - and the other
inhibiting - tamoxifen - were applied. Estradiol added to a culture
containing decreasing concentrations of isotretinoin (from 3x10(-3) to
3x10(-8) M) caused a statistically significant reduction in the
percentage of [3H]thymidine incorporation into the cancer cell line
MCF-7, compared to the 17 beta estradiol group (189.25%+/-62.64,
control=100%, p<0.05). In the group of decreasing tretinoin
concentrations, statistically significant differences were found only at
3x10(-3), 3x10(-4) and 3x10(-8) M. Following culture supplementation
with tamoxifen (1 microM), statistically significant differences were
observed only at the highest concentrations of both retinoids (3x10(-3)
and 3x10(-4) M). The evaluation of breast carcinoma cells with a
positive immunocytochemical reaction to PCNA and Ki-67 has revealed that
isotretinoin reduces their percentage in the most determined and
statistically significant way (38.00%+/-2.58 and 39.25%+/-3.09),
compared to the control group (86.50%+/-9.20 and 100%+/-3.87, p<0.001
and p<0.0001) and to the estradiol group (87.00%+/-6.79 and
86.10%+/-7.0, p<0.001). Apart from their blocking effect on the cell
cycle, retinoids also induce the apoptotic pathway.
2
UI - 11844540
AU - Goodare H; Dimmer C; Page K
TI -
Screening mammography: setting the record straight.
SO - Lancet 2002 Feb 2;359(9304):442
3
UI - 10920144
AU - Vickers A; Christos P
TI -
Bezwoda: evidence of fabrication in original article.
SO - J Clin Oncol 2000 Aug;18(15):2933
4
UI - 11078504
AU - Vickers A; Christos P
TI -
Re: "Bezwoda: evidence of fabrication in original article".
SO - J Clin Oncol 2000 Nov 15;18(22):3875
5
UI - 11544827
AU - Semiglazova TIu; Gershanovich ML
TI -
[Xeloda (capecetabine) in the treatment of disseminated breast cancer
after failure with anthracyclines and taxanes]
SO - Vopr Onkol 2001;47(3):298-302
AD - N.N. Petrov Research Institute of Oncology, Ministry of Health of the
RF, St. Petersburg.
Xeloda (capecetabine) has been tested for efficacy and toxicity in
treating disseminated breast cancer after the potential of anthracycline
(group 1) chemotherapy, anthracyclines plus taxanes (group 2) was
exhausted. The patients included into the study (54) were divided into
groups 1 (33) and 2 (21). Apparent response was in 24 and 21%,
respectively. The drug may be used both in out-patients and those
refractory to anthracycline chemotherapy and anthracyclines plus taxanes
due to moderate toxicity, slight myelodepression and absence of alopecia
which seldom makes treatment useless.
6
UI - 11544828
AU - Sidorenko IuS; Vladimirova LIu; Frantsiiants EM
TI -
[Effect of chemotherapeutical agents on the structure and function of
blood serum albumin in breast cancer]
SO - Vopr Onkol 2001;47(3):303-6
AD - Research Institute of Oncology, Ministry of Health of the RF,
Rostov-on-Don.
Superoxide-removing activity, the number of sulfo-hydryl NH2-groups and
groups, mean mass molecular concentration, free and antioxidant activity
of albumin were determined in blood serum and its albumin fraction in 20
patients with breast cancer T3-4N1-2Mo, before and after incubation with
cyclophosphamide, adriablastin, methotrexate and vincristine at
concentrations used in clinic. Our data suggested that, following
incubation with blood plasma, chemotherapeutic drugs bound to albumin
fraction and protein fragmentation took place. Preincubation of blood
plasma with the drugs and their immobilization on albumin molecules
caused protein fragmentation to occur. Fragments having pro-oxidant
properties might have been absorbed and fixed by both tumor tissues and
any others thus creating a pool of fast-dividing cells and organs.
Therefore, cytostatic drugs can exert enhanced antitumor action and, at
the same time, a highly toxic effect when administered with autoplasma
during chemotherapy.
7
UI - 11596702
AU - Ohsfeldt RL; O'Connor LJ; Kemner JE; Solomon TE
TI -
Patterns of physician-reported diagnoses for women receiving raloxifene
prescriptions.
SO - Am J Health Syst Pharm 2001 Oct 1;58(19):1846-9
AD - College of Public Health, University of Iowa, Iowa City 52242, USA.
robert-ohsfeldt@uiowa.edu
8
UI - 11723746
AU - Ito Y; Aiba K; Horikoshi N; Saotome T; Irie T; Sugiyama K; Nakane M;
TI -
Hashimoto D; Yoshida N; Mizunuma N; Takahashi S; Tanigawara Y
Dose-finding phase I study of simultaneous weekly infusion with
doxorubicin and docetaxel in patients with advanced breast cancer.
SO - Int J Clin Oncol 2001 Oct;6(5):242-7
AD - Department of Medical Oncology, Cancer Institute Hospital, Cancer
Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1
Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan. yito@jfcr.or.jp
BACKGROUND: Combination therapy with doxorubicin (DOX) and docetaxel
(DOC), given 3 weeks apart, is one of the standard regimens used for
treating metastatic breast cancer, but it frequently generates febrile
neutropenia. To find a safer regimen with less myelotoxicity and the
appropriate dose intensity, we conducted a phase I study of simultaneous
weekly infusion with DOX and DOC. METHODS: Twenty-five patients with
advanced breast cancer were treated with an intravenous push-injection
of DOX that was immediately followed by a 1-h infusion of DOC. This was
repeated every week for at least 6 weeks. The premedication employed was
three 4-mg doses of dexamethasone every week. Patients were divided into
four groups for which the doses of DOX and DOC were escalated in 5-mg/m2
increments. RESULTS: In the 18 patients who were treated with DOX 15 or
20 mg/m2 and DOC 25 mg/m2, or lower, the regimen was found to be
tolerable, without febrile episodes. The regimen with 20 mg/m2 of DOX
and 30 mg/m2 of DOC was the maximum tolerated dose. Other indications of
grade 3 toxicity included asthenia in 4% of patients, anorexia in 8%,
and vomiting in 8%. Of the 25 patients, 14 had a partial response. The
overall response rate was 56% (95% confidence interval [CI], 35% to
77%). The recommended dose for further trial was 20 mg/m2 of DOX and 25
mg/m2 of DOC. CONCLUSION: Simultaneous weekly infusion with DOX and DOC
was feasible, with modest neutropenia and preserved dose intensity. This
regimen may be helpful in the management of patients with advanced
breast cancer.
9
UI - 11840607
AU - Aziz Z; Sana S; Akram M; Ilyas N
TI -
Phase 1 trial of ifosfamide and adriamycin in metastatic breast cancer.
SO - J Pak Med Assoc 2001 Nov;51(11):400-5
AD - Department of Oncology, Allama Iqbal Medical College, Lahore.
OBJECTIVE: A Phase 1 trial was conducted in patients with estrogen
negative receptors (ER) or hormone refractory metastatic breast cancer
to determine the maximum tolerated dose (MTD) of ifosfamide with a fixed
dose of doxorubicin. A secondary objective was to determine the efficacy
of the combination in metastatic breast cancer. METHODS: Fifteen
patients were entered in the study in cohorts of three patients at each
dose level of ifosfamide. The dose of doxorubicin was fixed at 45 mg/m2.
Five different dose levels of ifosfamide were tested ranging from dose
level 1 of 1.5 gms/m2 day 1-3 to level V at 2.5 gms/m2 day 1-3. RESULTS:
Dose escalation of ifosfamide was stopped at 2.5 gms/m2. The MTD of
ifosfamide was 2.25 gms/m2 day 1-3 in combination with doxorubicin. All
patients in the study were assessable for toxicity. Neutropenia and
thrombocytopenia were the major dose limiting toxicities. Other
toxicities included anemia, confusion and hematuria. Objective responses
were documented in 11 of 15 patients (73.3%). Median time to treatment
failure (TTF) was 13 months. Median overall survival (OS) was 18 months.
CONCLUSION: The combination of ifosfamide and doxorubicin was a
practical well tolerated regimen. There was substantial evidence of
clinical activity in this phase I trial. This combination should be
further evaluated, as an attractive alternative to taxanes for patients
in developing countries where cost effectiveness is important.
10
UI - 11865621
AU - Tokura H; Ikeda T; Kitajima M
TI -
[Intra-arterial infusion chemotherapy for breast cancer]
SO - Gan To Kagaku Ryoho 2002 Feb;29(2):176-81
AD - Department of Surgery, Keio University Hospital, 35 Shinanomachi,
Shinjuku-ku, Tokyo 160-8582, Japan.
Intra-arterial infusion chemotherapy has a significant effect in
down-staging locally advanced breast cancer by providing a high dose
intensity. It is also used for the treatment of liver metastasis. A
better response rate and lower incidence of adverse effects are reported
when patients are treated with intra-arterial infusion chemotherapy than
with systemic chemotherapy using the same dose of the same drugs. Recent
advances in devices such as access ports and portable infusion pumps
make it possible to perform intra-arterial infusion chemotherapy
repeatedly and safely. However, it remains uncertain whether or not
intra-arterial infusion chemotherapy can improve the prognosis of cancer
patients because of the lack of data from phase III trials. Accordingly,
further studies including combined use of systemic chemotherapy are
mandatory to the control of micrometastases outside the target organ.
11
UI - 11865627
AU - Kokufu I; Taniguchi H; Kimura F; Fukuda K; Yamamoto M; Yano T; Yamada K
TI -
[Weekly paclitaxel therapy for metastatic breast cancer]
SO - Gan To Kagaku Ryoho 2002 Feb;29(2):221-6
AD - Dept. of Surgery, Itami City Hospital.
We treated 12 patients with metastatic breast cancer with weekly
paclitaxel therapy. Paclitaxel was administrated by 1 hour infusion at a
dose of 80 mg/m2 after short premedication every week on an outpatient
basis. Administration was continued for 3 weeks followed by 1 week rest.
All patients had received prior metastatic chemotherapy, and prior
anthracycline therapy was done in 66.7% of the patients. Partial
responses were observed in 66.7% of the patients and progressive disease
in 33.3%. The response rate was 66.7%. Responses were observed in 62.5%
of the patients with prior anthracycline therapy. Grade 3/4 leukopenia
and neutropenia occurred in 25% of the patients, respectively, and no
grade 3/4 peripheral neuropathy was observed. Dyspnea occurred in 25% of
the patients and was grade 3 in 16.7%. Dyspnea is thought to be one of
the adverse events requiring caution with weekly paclitaxel
administration. Weekly paclitaxel therapy is effective and well
tolerated in patients with metastatic breast cancer.
12
UI - 11865628
AU - Uno Y; Hirano M; Murakami N; Kikuchi T; Nozawa H; Okuda T; Oya J;
TI -
Kikkawa H
[Weekly administration of low-dose paclitaxel for advanced or metastatic
breast cancer]
SO - Gan To Kagaku Ryoho 2002 Feb;29(2):227-32
AD - Dept. of Surgery, Koseiren Takaoka Hospital.
The activity and toxicity of a weekly infusion of low-dose paclitaxel
was studied. Twelve patients with metastatic or advanced breast cancer
received paclitaxel (80 mg/m2 over 1 h) every week. Administration was
continued for 6 weeks with two weeks rest until disease progression or
limiting toxicity. Dexamethasone 20 mg, diphenhydramine 50 mg, and
ranitidine 50 mg were given prior to each dose of paclitaxel. Six
patients had received prior standard CMF therapy, and four patients had
received CMF and docetaxel therapy. Two patients had not received prior
therapy. The overall response rate was 58% with 17% complete responses
and 42% partial responses. Responses were observed in both patients
without prior therapy, and in five of 10 (50%) with prior therapy. Grade
3/4 neutropenia occurred in one patient; febrile neutropenia was not
observed. There was no neuropathy or hypersensitivity. Weekly paclitaxel
is active and well tolerated in patients with metastatic or advanced
breast cancer. This schedule allows a high cumulative dose of paclitaxel
without major myelo- or neurotoxicity. This weekly regimen deserves
further exploration.
13
UI - 11535996
AU - Morandi P; Ruffini PA; Benvenuto GM; La Vecchia L; Mezzena G; Raimondi R
TI -
Serum cardiac troponin I levels and ECG/Echo monitoring in breast cancer
patients undergoing high-dose (7 g/m(2)) cyclophosphamide.
SO - Bone Marrow Transplant 2001 Aug;28(3):277-82
AD - Division of Medical Oncology, San Bortolo Hospital, Vicenza, Italy.
High-dose cyclophosphamide (HD-CTX) is largely employed in high-dose
chemotherapy (HD-CHT) protocols. HD-CTX dose-limiting toxicity expresses
itself as cardiac toxicity which is fatal in a minority of patients. The
pathophysiology of HD-CTX-associated cardiotoxicity is still poorly
understood. Autopsy studies in patients who died from acute
HD-CTX-induced cardiac toxicity revealed hemorrhagic myocardial cell
death and interstitial edema. Recently troponins, in particular troponin
I (cTnI), have been found to represent a uniquely sensitive and specific
marker of myocyte membrane integrity and therefore to increase in
response to minimal myocardial cell damage in different settings,
including doxorubicin-induced cardiotoxicity. We performed a
multiparametric cardiologic monitoring in 16 consecutive breast cancer
patients undergoing HD-CTX by means of serial ECG registrations and
cardiac enzymes (CPK, CPK-MB and cTnI) determinations plus
echocardiography in order to clarify acute cardiac events following
HD-CTX administration. Neither overt cardiac toxicity nor cardiac
enzymes elevation were recorded. Serial ECGs revealed in six cases
little and reversible reduction of QRS voltage and/or ST abnormalities.
Echo monitoring showed in four cases mild and transient increase of LV
diastolic/systolic diameter/volume without decrease of FS% or EF% below
normal values: in two of them abnormalities of diastolic function (E/A
mitral doppler ratio) were also recorded. We conclude that our protocol
of HD-CTX administration does not cause myocardial cell damage as
analyzed by serum cTnI levels, thus suggesting that myocyte membrane
injury may not be the first direct mechanism of HD-CTX cardiotoxicity.
ECG (ie QRS voltages ) and Echo (ie E/A ratio) monitoring leads us to
hypothesize that slight interstitial edema with reduction of LV
diastolic compliance may be initial signs of cardiac dysfunction in this
clinical setting.
14
UI - 11843850
AU - de Sousa JA; de Seixas MT; de Lima GR; Baracat EC; Gebrim LH
TI -
Evaluation of monoclonal antibody MIB-1 in the mammary epithelium
adjacent to fibroadenomas in premenopausal women treated with tamoxifen.
SO - Breast J 2001 Nov-Dec;7(6):392-7
AD - Department of Gynecology, Federal University of Sao Paulo, Sao Paulo,
Brazil. drjuarez@uol.com.br
The purpose of this study was to study the monoclonal antibody MIB-1 in
the normal breast epithelium adjacent to a fibroadenoma in women in the
luteal phase of the menstrual cycle who were treated with tamoxifen at
doses of 10 and 20 mg for 22 days. The proliferative activity of the
mammary epithelium adjacent to the fibroadenoma was studied by
immunohistochemistry on the basis of the monoclonal antibody MIB-1
(Immunotech, catalog No. 0505, lot 001). The study was randomized and
double blind and was conducted on 44 women with fibroadenomas divided
into three groups: A (n=16, placebo), B (n=15, tamoxifen, 10 mg), and C
(n=13, tamoxifen, 20 mg). Tamoxifen was administered for 22 days
starting on the 2nd day of the menstrual cycle, and a biopsy was taken
on the 23rd day. Serum estradiol, progesterone, sex hormone binding
globulin, follicle-stimulating hormone, luteinizing hormone, and
prolactin were measured before treatment (21st and 24th day of the
previous menstrual cycle) and on the day of the biopsy. The mean
percentage of stained nuclei per 1,000 cells was 9.2 in group A, 4.5 in
group B, and 3.2 in group C. The Fisher's test revealed that tamoxifen
significantly reduced MIB-1 at doses of 10 and 20 mg compared with the
placebo group (p < 0.0001), with no significant differences between
doses in terms of proliferative activity (p=0.21). Groups B and C
presented a significant increase in progesterone (p=0.038), estradiol (p
< 0.001), and sex hormone binding globulin (p=0.001) levels. Elevation
of serum follicle-stimulating hormone concentration (p=0.0045) and a
fall in prolactin levels (p=0.0055) were observed. We conclude that
tamoxifen significantly reduced the proliferative activity of the
mammary epithelium at the doses of 10 and 20 mg/day.
15
UI - 11843855
AU - Fiegl M; Kaufmann H; Steger GG
TI -
Ulcerative breast cancer: case report and review of management.
SO - Breast J 2001 Nov-Dec;7(6):422-6
AD - First Department of Internal Medicine, Division of Clinical Oncology,
University of Vienna, Vienna, Austria.
In the literature, there is an astonishingly small amount of information
on specific treatment modalities of locally advanced, ulcerated breast
cancer. Here we present a case report and a literature review on
ulceration in breast cancer. An older, so far untreated woman with
complete ulcerative destruction of her right breast was inoperable
because of the extent of the tumor. Primary anthracycline-based
chemotherapy and hormonal therapy led to major tumor shrinkage with
complete ulcer healing, which was maintained for nearly 2 years. There
is increasing evidence from the literature that primary chemotherapy may
particularly benefit patients with inoperable ulceration, as also
illustrated by our case.
16
UI - 11843860
AU - Kotiloglu G; Aki ZS; Ozyilkan O; Kutlay L
TI -
Tamoxifen-induced cirrhotic process.
SO - Breast J 2001 Nov-Dec;7(6):442-3
AD - Department of Internal Medicine, Bayindir Medical Center,
Sogutozu/Ankara, Turkey.
17
UI - 11810037
AU - Blackstein M; Vogel CL; Ambinder R; Cowan J; Iglesias J; Melemed A
TI -
Gemcitabine as first-line therapy in patients with metastatic breast
cancer: a phase II trial.
SO - Oncology 2002;62(1):2-8
AD - Mount Sinai Hospital, Toronto, Canada. martin.blackstein@utoronto.ca
OBJECTIVES: This phase II study was conducted to evaluate the efficacy
and safety of gemcitabine in patients with metastatic breast cancer
(MBC). METHODS: Women with histologically or cytologically confirmed
bidimensionally measurable MBC not amendable to curative surgery or
radiation were eligible. Prior chemotherapy for metastatic disease was
not permitted. Patients received gemcitabine 1,200 mg/m(2) on days 1, 8
and 15 for 3 weeks every 28 days for a maximum of 8 cycles. RESULTS:
Thirty-nine patients, with a median age of 58 years, were enrolled. The
overall response rate for the 35 evaluable patients was 37.1% (95%
confidence interval [CI], 21.5-55.1%), with 2 complete responses and 11
partial responses. Median time to progression and survival were 5.1
months (95% CI, 3.5-8.8 months) and 21.1 months (95% CI, 11.0-26.9
months), respectively. Chemotherapy was well tolerated, with a median of
4 cycles completed. Grade 4 toxicities were 1 infection and 1 abnormal
pulmonary function. Grade 3 neutropenia and thrombocytopenia occurred in
30.3% and 6.3% of patients, respectively. The most common grade 3
non-hematologic toxicity was nausea/vomiting (10.3%). Five of 21
patients had improved Karnofsky performance status (KPS) scores.
CONCLUSION: Single-agent gemcitabine is active and well tolerated as
first-line treatment in patients with MBC. Copyright 2002 S. Karger AG,
Basel
18
UI - 11810040
AU - Frasci G; D'Aiuto G; Comella P; Thomas R; Capasso I; Botti G; Cortino
TI -
GR; Di Bonito M; Rubulotta R; Vallone P; Comella G
A phase I-II study on a
gemcitabine-cyclophosphamide-fluorouracil/folinic acid triplet
combination in anthracycline- and taxane-refractory breast cancer
patients.
SO - Oncology 2002;62(1):25-32
AD - Division of Medical Oncology A, National Tumor Institute of Naples,
Naples, Italy. gifrasci@sirio-concology.it
PURPOSE: To define the cyclophosphamide (CTX) maximal tolerated dose
when combined with fixed doses of gemcitabine, fluorouracil (5-FU) and
folinic acid (leucovorin, LFA) in metastatic breast cancer patients
pretreated with anthracyclines and taxanes. METHODS: Metastatic breast
cancer patients aged < or = 75 years, with ECOG performance status 0-2,
were eligible, provided that they had received previous anthracycline-
and taxane-based chemotherapy for the advanced disease. Chemotherapy
consisted of gemcitabine 1,000 mg/m(2), 5-FU 425 mg/m(2), LFA 100
mg/m(2) and escalating doses of CTX, starting from 500 mg/m(2), on days
1 and 8 every 3 weeks. The dose escalation was stopped if dose-limiting
toxicity (DLT) occurred in > 33% of patients of a given cohort. After
the definition of DLT, a further escalation with the addition of
granulocyte colony-stimulating factor (G-CSF; on days 3-5 and 10-12) was
through seven different cohorts. The dose escalation was stopped at the
CTX dose of 600 mg/m(2) since 3/6 patients showed DLT. A further dose
escalation was attempted in the presence of G-CSF support. A CTX dose of
800 mg/m(2) proved to be safe and was chosen for the phase II. A total
of 33 patients were treated at this dose level. The treatment was fairly
well tolerated, grade 3-4 neutropenia and thrombocytopenia occurring in
38 and 16% of patients, respectively. No cases of sepsis or bleeding
were registered. Four patients required a packed red blood cell
transfusion. Severe nonhematologic toxicity was also uncommon, occurring
in 10 patients. Three complete and 24 partial responses were recorded
for an overall response rate of 38% (95% CI = 26-50). Two complete and
12 partial responses were recorded in the 33 patients treated in the
phase II for an overall response rate (ORR) of 42% (95% CI = 25-61).
CONCLUSIONS: The gemcitabine-CTX-5-FU/LFA combination is a
well-tolerated treatment for poor-prognosis breast cancer patients with
previous exposure to anthracyclines and taxanes. With the addition of
G-CSF, a cumulative CTX dose of 1,600 mg/m(2) can be safely delivered
every 3 weeks. The evidence of an ORR approaching 40% is very promising
and justifies further evaluations in this subset of patients. Copyright
2002 S. Karger AG, Basel
19
UI - 11810041
AU - Brugnatelli S; Danova M; De Bella MT; Vaglica M; Manuguerra G; Riccardi
TI -
A; Palmeri S
Weekly administration of gemcitabine plus docetaxel in patients with
advanced breast cancer: a phase 1 study.
SO - Oncology 2002;62(1):33-8
AD - Internal Medicine and Medical Oncology, University and IRCCS S. Matteo,
Pavia, Italy.
OBJECTIVE: This study was designed to determine the maximum tolerable
dose (MTD) of gemcitabine plus docetaxel, both given on a weekly
schedule, in patients with pretreated metastatic breast cancer (MBC).
METHODS: Heavily pretreated patients with MBC, aged 18-75 years with
World Health Organization performance status of 0-2 were enrolled. Three
escalating weekly doses of docetaxel (30, 35 and 40 mg/m(2)) followed by
a weekly fixed dose of gemcitabine, 800 mg/m(2), were administered on
days 1, 8 and 15 of a 28-day cycle. Dose-limiting toxicity (DLT)
included grade > 3 hematologic toxicity and grade > 2 stomatitis,
asthenia, diarrhea or organ-specific toxicity (except alopecia). Dose
escalation was stopped if > or = 3 of 5 patients at any dose level
experienced DLT. RESULTS: Eighteen patients (median age 56 years)
received a mean of 4.1 (range 1-6) cycles. Asthenia, stomatitis and
leukopenia were the main DLTs. One of 5 patients had DLT at dose level 1
and 2 of 5 patients at dose level 2. At dose level 3, 3 of 5 patients
had DLTs. Three additional patients treated at dose level 3 confirmed
that the MTD had been reached. Therefore, the recommended docetaxel dose
in combination with gemcitabine 800 mg/m(2) for phase II studies was
established at the next lower dose, 35 mg/m(2). Of 12 evaluable
patients, 7 (58%) achieved an objective response. CONCLUSIONS:
Gemcitabine 800 mg/m(2) plus docetaxel 35 mg/m(2) on days 1, 8 and 15 of
a 28-day cycle is a safe regimen which shows activity in heavily
pretreated patients with MBC. Further phase II investigations with this
combination are now warranted. Copyright 2002 S. Karger AG, Basel
20
UI - 11856154
AU - Rivera E; Holmes FA; Buzdar AU; Asmar L; Kau SW; Fraschini G; Walters R;
TI -
Theriault RL; Hortobagyi GN
Fluorouracil, doxorubicin, and cyclophosphamide followed by tamoxifen as
adjuvant treatment for patients with stage IV breast cancer with no
evidence of disease.
SO - Breast J 2002 Jan-Feb;8(1):2-9
AD - Department of Breast Medical Oncology, The University of Texas M. D.
Anderson Cancer Center, Houston, Texas 77030-4009, USA.
We conducted a single-institution study to determine whether local
therapy plus six cycles of chemotherapy with 5-fluorouracil,
doxorubicin, and cyclophosphamide (FAC) followed by 5 years of tamoxifen
is superior to local treatment alone in terms of disease-free survival
(DFS) and overall survival (OS) in patients with stage IV breast cancer
with no evidence of disease (stage IV-NED breast cancer). Patients with
breast cancer were eligible if they had histologic proof of a
locoregional or distant recurrence that had been curatively resected,
irradiated, or both and had no other evidence of disease. Patients who
had received prior anthracycline therapy were not eligible. All patients
received six cycles of intravenous FAC, with cycles repeated every 3
weeks. After completion of chemotherapy, patients whose tumors had not
previously demonstrated resistance to tamoxifen and had positive or
unknown estrogen receptor status received tamoxifen 20 mg by mouth daily
for 5 years. Patients in this study were compared with a historical
control population (patients with stage IV-NED breast cancer who never
received systemic therapy) as well as with the patients in two
previously reported trials of chemotherapy for stage IV-NED disease.
Forty-seven patients were registered, but only 45 were evaluable. There
was a highly statistically significant difference ( p < 0.001) in OS and
DFS among the four groups, with patients in our most recent study having
the best OS and DFS at 3 years compared with the control group (84% vs.
55% and 66% vs. 11%, respectively). When patients in all four groups
were analyzed together in search of prognostic factors, we found that
patients whose primary tumors had negative axillary lymph nodes had a
statistically significant improvement in OS and DFS ( p < 0.01) compared
with patients with positive axillary lymph nodes. No survival
differences were found between patients with positive and those with
negative hormone receptor status. This study demonstrates a benefit in
terms of OS and DFS for patients with stage IV-NED breast cancer who
receive doxorubicin-based adjuvant chemotherapy. The benefit was greater
on patients with node-negative primary tumors. In patients with stage
IV-NED disease, doxorubicin-based chemotherapy should be considered
standard treatment after adequate local control is achieved.
21
UI - 11852998
AU - Auerbach M; Elias EG; Orford J
TI -
Experience with methotrexate, 5-fluorouracil, and leucovorin (MFL): a
first line effective, minimally toxic regimen for metastatic breast
cancer.
SO - Cancer Invest 2002;20(1):24-8
AD - Division of Medical Oncology, Franklin Square Hospital Center,
Baltimore, Maryland 21237, USA.
Thirty-two women with untreated metastatic breast cancer were treated
with 100 mg/M2 i.v. methotrexate (MTX), 600 mg/M2 5-fluorouracil (5FU)
and leucovorin 15 mg orally every 6 hr, 24 hr after MTX (MFL) on days 1
and 8 every 28 days. Stratification was according to sites of metastases
(mets), adjuvant (adj), chemotherapy (CTX), and/or hormonal therapy or
no adj therapy (Tx). Treatment continued until documented radiographic
or clinical disease was in progression. Toxicity was mild, consisting of
only minimal elevations of transaminases and mild cytopenias. There was
no pulmonary toxicity. There were no hospitalizations, treatment delays
or cessations for toxicity. One patient with skeletal mets had a
complete response and 7 had partial responses. The overall median
progression free survival (PFS) was 13.8 months (mos). Eighteen patients
with skeletal mets had PFS from 7-70 mos (median 15.9). Five patients
with lung mets only had PFS from 6-20 mos (median 9.8 mos). Patients
with liver alone or with other visceral mets showed progression within
2-5 mos. However, patients with bone and visceral mets without liver
involvement had PFS from 8-50 mos (median 20.5). Of 21 adj Tx failures
the median PFS was 8.8 mos (2-94). Six who received adj CTX had a median
PFS of 7.6 mos (3-12) and 4 tamoxifen (tam) failures a median PFS of 11
mos (8-15). Eleven patients who received adj CTX+tam had a median PFS of
8.5 mos (2-94). Six patients received tam at adj failure and MFL at
progression. These six had a median PFS of 19.8 mos (8-50). The patients
(six, who received no prior adj Tx) had a median PFS of 24.3 (8-70). MFL
is as effective in achieving clinical remissions in metastatic breast
cancer, is inexpensive and is far less toxic than other CTX regimes. MFL
should strongly be considered as first line Tx.
22
UI - 11852999
AU - Ibrahim NK; Rahman Z; Valero V; Murray JL 3rd; Frye D; Hortobagyi GN
TI -
Phase I study of vinorelbine and docetaxel with granulocyte
colony-stimulating factor support in the treatment of metastatic breast
cancer.
SO - Cancer Invest 2002;20(1):29-37
AD - Department of Breast Medical Oncology, University of Texas M.D. Anderson
Cancer Center, Houston 77030-4009, USA. nibrahim@mdanderson.org
PURPOSE: Vinorelbine and docetaxel are two active agents in the
treatment of metastatic breast cancer. When given together, these drugs
exhibit synergistic antitumor activity without significant
pharmacokinetic interaction. The dose-limiting toxicities of this
combination are neutropenic fever and mucositis. Adding granulocyte
colony-stimulating factor (G-CSF) might lessen the toxicity and increase
the maximum tolerated dose (MTD) of this combination. The aim of this
study was to determine the MTD of vinorelbine and docetaxel given in
in this study. All patients had received doxorubicin-based therapy, and
46% had received paclitaxel in the adjuvant or neoadjuvant setting.
Patients were treated with vinorelbine at a starting dose of 20 mg/m2
intravenously over 10 min on days 1 and 5 and docetaxel at a starting
dose of 85 mg/m2 intravenously over 1 hr on day 1, following the
vinorelbine. Treatments were repeated every 21 days. Prophylactic G-CSF
5 mcg/kg was given subcutaneously on days 3-10. Toxicity was graded
according to the National Cancer Institute's grading system. RESULTS: A
total of 65 cycles was administered at dose levels 0, -1, -2, and -3.
The median absolute granulocyte count nadir for all courses was 200
mm(-3) (range, 0.1-7700 mm(-3)), and the median time to this nadir was 9
days (range, 7-30). The median platelet nadir was 163 (range, 27-401 k),
and the median time to this nadir was 8 days (range, 7-30). The most
common grade 3 nonhematologic toxicities for all courses were fatigue
and myalgia, which occurred in 32 and 10 cycles, respectively.
Neutropenic fever was encountered in 11 cycles. Three patients developed
colitis-like pictures, two of whom died as a result. Consequently, the
protocol was closed to accrual before a MTD was reached. CONCLUSION: The
combination of vinorelbine, docetaxel, and G-CSF in our hands has proven
to be a toxic regimen, even when relatively low doses of vinorelbine and
docetaxel are given. Meticulous observation of patients receiving this
combination is warranted since the combination resulted in two deaths in
this study.
23
UI - 11681532
AU - Sjostrom J; Alfthan H; Joensuu H; Stenman UH; Lundin J; Blomqvist C
TI -
Serum tumour markers CA 15-3, TPA, TPS, hCGbeta and TATI in the
monitoring of chemotherapy response in metastatic breast cancer.
SO - Scand J Clin Lab Invest 2001;61(6):431-41
AD - Department of Oncology, Helsinki University Hospital, Finland.
johanna.sjostrom@hus.fi
The clinical utility of CA 15-3, polypeptide specific antigen (TPS),
tissue polypeptide antigen (TPA), human chorionic gonadotropin (hCGbeta)
and tumour-associated trypsin inhibitor (TATI) as indicators of
chemotherapy response was assessed in advanced breast cancer. Serum was
prospectively collected in one center before treatment (after the first
course of chemotherapy) and at response evaluation from 57 patients
taking part in a multicentre randomized trial comparing docetaxel with
sequential methotrexate and 5-fluorouracil in the treatment of advanced
breast cancer. The pretreatment levels of the serum markers were not
predictors of the later response to treatment. Changes in the TPS level
showed the strongest association with clinical response after the first
course of chemotherapy and CA 15-3 at the best response evaluation.
However, distinct mismatches occurred with every marker. The most
problematic error was an increase in marker levels in patients with
clinical responses, which might have caused interruption of therapy.
This occurred in 8% and 17% of patients after the first course of
chemotherapy and in 4% and 17% of patients at the best response
evaluation with CA 15-3 and TPS, respectively. Moreover, after the first
course of chemotherapy only 39% and 33% of the patients with progressive
disease could be identified on the basis of increasing levels of CA 15-3
and TPS. respectively. Later, at clinical disease progression, TPA and
TPS were found to be better indicators of disease progression than CA
15-3. In conclusion, changes in CA 15-3 or TPS levels usually correlate
with clinical response, but owing to distinct discordances, they should
not be used as sole indicators of response to chemotherapy in advanced
breast cancer.
24
UI - 11549446
AU - Chibale K; Ojima I; Haupt H; Geng X; Pera P; Bernacki RJ
TI -
Modulation of human mammary cell sensitivity to paclitaxel by new
quinoline sulfonamides.
SO - Bioorg Med Chem Lett 2001 Sep 17;11(18):2457-60
AD - Department of Chemistry, University of Cape Town, Rondebosch 7701, South
Africa. chibale@science.uct.ac.za
Sulfonamide derivatives of chloroquine and primaquine were synthesised
and evaluated against both paclitaxel-sensitive and paclitaxel-resistant
mammarian cancer cell lines. All derivatives exhibited at least 96% MDR
reversal activity when co-administered with paclitaxel at 5 microM. The
best compound, a chloroquine derivative, exhibited 99% MDR reversal
activity when co-administered with paclitaxel at 1 microM. Molecular
modelling studies reveal that these derivatives share a common
pharmacophore with taxane MDR reversal agents.
25
UI - 11810777
AU - Jiang Z; Song S; Liu X
TI -
[Prospective randomized trial on the efficacy of adjuvant endocrine
therapy for ER-positive breast cancer patients after radical mastectomy]
SO - Zhonghua Zhong Liu Za Zhi 2001 Sep;23(5):420-2
AD - Department of Breast Cancer, Hospital 307, Academy of Military Medical
Sciences, Beijing 100039, China.
OBJECTIVE: To asses the efficacy of adjuvant endocrine therapy in
ER-positive breast cancer patients after radical mastectomy. METHODS:
369 estrogen receptor (ER)-positive breast cancer patients were divided
into two groups after radical mastectomy: 1. Endocrine group (N-194).
The postmenopausal patients in this group received oral tamoxifen (TAM)
for five years and the premenopausal patients were first treated with
bilateral ovary ablation and, then, given TAM for five years. 2. The
chemotherapy group patients (N-175) received CTX + MTX + 5-Fu + VCR +
DXM) (CMFVP) or CTX + MTX + 5-Fu (CMF) multi-drug chemotherapy. RESULTS:
Postmenopausal patients in the endocrine and chemotherapy groups gave
disease-free survival rates (DFSR) of 78.4% and 45.4% (P < 0.01). Their
overall survival rates were 83.3% and 52.9% (P < 0.05). The
premenopausal patients gave DFSR of 72.8% and 35.7% (P < 0.01), and
their overall survival rates were 80.7% and 60.6% (P < 0.05). But, no
significant difference was observed in the stage I patients and those
having > or = 8 axillary lymph node metastases (P > 0.05). CONCLUSION:
For ER-positive breast cancer patients, the adjuvant endocrine therapy
gives results superior or equal to multi-drug chemotherapy after radical
mastectomy.
26
UI - 11810778
AU - Shi J; Fang G; Sheng Y
TI -
[Neo-adjuvant chemotherapy for breast cancer]
SO - Zhonghua Zhong Liu Za Zhi 2001 Sep;23(5):423-5
AD - Changhai Hospital, Shanghai 200433, China.
OBJECTIVE: To study the value and indications of a neo-adjuvant
chemotherapy for breast cancers. METHODS: Forty-three breast cancer
patients were given the NF neo-adjuvant chemotherapy (Navelbine 25 mg/m2
and 5-Fu 500 mg/m2) for 3 cycles before the operation. Epirubicin (EPI
40 mg/m2) was added in patients with locally advanced lesions. G-CSF 75
micrograms subcutaneous injection was used to increase the white count
as needed. RESULTS: The overall response rate was 95.0%. Pre-operative
neo-adjuvant chemotherapy showed CR in 3 patients (7.5%) and PR in 35
patients (87.5%) even though 2 patients (5.0%) were refractory. The
follow-up ranged from 4 to 37 months (median 20 months). All patients
are alive though 4 have developed recurrence or metastasis. CONCLUSION:
The pre-operative neo-adjuvant chemotherapy may preferably be given in 3
cycles from which those who benefit most are the breast cancer patients
with inoperable lesions and who are planned to undergo breast-preserving
surgery.
27
UI - 11848474
AU - Schultz RM; Dempsey JA
TI -
Sequence dependence of Alimta (LY231514, MTA) combined with doxorubicin
in ZR-75-1 human breast carcinoma cells.
SO - Anticancer Res 2001 Sep-Oct;21(5):3209-14
AD - Cancer Research Division, Lilly Research Laboratories, Eli Lilly and
Company, Indianapolis, IN 46285, USA.
Alimta is a new-generation antifolate with inhibitory activity against
multiple enzymes, including thymidylate synthase, glycinamide
ribonucleotide formyltransferase and dihydrofolate reductase. Alimta is
undergoing broad phase II evaluation as a single agent, and preliminary
results show responses in several tumor types, including breast
carcinoma. Doxorubicin is often used in combination chemotherapy of
breast cancer. Because the two drugs have mechanisms of action that
might be complementary, we investigated a possible synergism between
doxorubicin and Alimta on growth inhibition of ZR-75-1 human breast
carcinoma cells. Cytostatic activity was evaluated using semi-automated
MTT assays, and drug interactions were determined using CalcuSyn
(Chou/Hayball) multiple drug effect analyses. The cells were exposed to
Alimta or doxorubicin as single agents and combinations for 24 hours
starting at the time of plating or for 72 hours starting 24 hours after
plating with a total culture time of 96 hours. Preincubation with Alimta
for 24 hours followed by exposure to doxorubicin for 72 hours resulted
in highly synergistic activity, whereas the opposite sequence or
simultaneous exposure produced mainly an additive response. DNA flow
cytometry studies indicated that Alimta causes a build-up of cells near
the G1/S interface after 24 hours of incubation. The data suggest that,
to obtain maximal antitumor activity, Alimta should precede doxorubicin
when the drugs are given in combination chemotherapy protocols.
28
UI - 11848526
AU - Pectasides D; Dimopoulos MA; Aravantinos G; Kalophonos HP; Papacostas P;
TI -
Briasoulis E; Cogas E; Papadimitriou C; Skarlos D; Kosmidis P;
Fountzilas G
First line combination chemotherapy with docetaxel and vinorelbine in
advanced breast cancer. A phase II study.
SO - Anticancer Res 2001 Sep-Oct;21(5):3575-80
AD - Metaxas Cancer Hospital, Piraeus, Greece.
We evaluated the efficacy and tolerance of the combination of docetaxel
and vinorelbine as first line treatment in metastatic breast cancer
(MBC). These agents have different mechanisms of action and both are
active in advanced breast cancer. Thirty-nine chemotherapy-naive for
metastatic disease patients were treated on an out-patient basis with
vinorelbine 20 mg/m2 i.v. on days 1 and 8 and docetaxel 85 mg/m2 i.v. on
day 8, every 3 weeks. Twenty-one (53.8%) patients had locoregional
disease, 30 (76.9%) had distant metastases and 20 (51.3%) had visceral
metastases. The intent-to-treat objective response rate (RR) was 48.75%
(19 out of 39 patients; 95% confidence interval (CI), 32.4% to 65.2%).
Four patients (10.25%) achieved a complete response (CR) (95% CI, 2.9%
to 24.2%) and 15 (38.5%) a partial response (PR) (95% CI, 23.4% to
55.4%). The median duration of response was 4 months, the median time to
progression (TTP) was 6 months and the median survival-time was 11.3
months. Grade 3 and/or 4 (3/4) anemia and thrombocytopenia occurred in
7.7% and 5.1% of patients, respectively. Twelve (30.7%) patients
developed grade 3/4 neutropenia and 7 (17.9 %) were complicated with
fever. Grade 3/4 diarrhea, nausea-vomiting, fatigue and constipation
were not a problem. Alopecia was universal. Grade 3/4 neurotoxicity was
evident in 2.6% of patients. None of the patients developed allergic
reaction or fluid retention. There was one treatment-related death due
to grade 4 neutropenia and sepsis. CONCLUSION: This combination of
docetaxel and vinorelbine, a non-anthracycline-containing regimen, is a
moderately effective regimen for the treatment of chemotherapy-naive
breast cancer patients with metastases, causing only mild to moderate
toxicity.
29
UI - 11870510
AU - Horiguchi J; Takei H; Koibuchi Y; Iijima K; Ninomiya J; Uchida K; Ochiai
TI -
R; Yoshida M; Yokoe T; Iino Y; Morishita Y
Prognostic significance of dihydropyrimidine dehydrogenase expression in
breast cancer.
SO - Br J Cancer 2002 Jan 21;86(2):222-5
AD - Second Department of Surgery, Gunma University Faculty of Medicine,
Showa-machi 3-39-15, Maebashi, Gunma 371-8511, Japan.
junhorig@showa.gunma-u.ac.uk
We have investigated dihydropyrimidine dehydrogenase expression as a
prognostic marker in breast cancer. A total of 119 women with breast
cancer undergoing surgery between 1985 and 1996 were included in this
study. Eighty-seven patients were treated with postoperative
chemotherapy including 5-fluorouracil or 5-fluorouracil derivatives.
Fifty-nine (50%) of 119 patients were determined to be
immunostaining-positive for dihydropyrimidine dehydrogenase. There was
no significant difference between dihydropyrimidine dehydrogenase
staining and tumour size, lymph node status, clinical stage, oestrogen
receptor status, histologic grade, or 5-fluorouracil administration.
When evaluated in patients treated with 5-fluorouracil or 5-fluorouracil
derivatives, patients with dihydropyrimidine dehydrogenase-positive
tumours had a significantly (P<0.05) poorer disease-free survival
compared to those with dihydropyrimidine dehydrogenase-negative tumour.
No conclusion can be drawn about the prognostic impact of
dihydropyrimidine dehydrogenase status i
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