Dear gail-ga
For your information, I found ‘basic’ trials which are detailed below,
Taxatere appears to be also known as Taxol or paclitaxel
Herceptin.com “Clinical Efficacy” excerpts
http://www.herceptin.com/herceptin/physician/j_profile/efficacy.htm
“In the landmark Phase III trial the addition of Herceptin to
chemotherapy was associated with a higher rate of response, a
significantly longer time to disease progression, and improved
survival. (Chemotherapy was either anthracyclines plus
cyclophosphamide or paclitaxel.)”
“Herceptin first-line in combination with a chemotherapy regimen of
paclitaxel or anthracyclines/cyclophosphamide:
More than doubles the response rate of paclitaxel alone (secondary
study endpoint)”
- Improvements in Overall Response Rates chart
http://www.herceptin.com/herceptin/physician/j_profile/pop_chart1.htm
“Significantly longer median time to disease progression (primary
study endpoint)”
- Improvements in Median Time to Disease Progression chart
http://www.herceptin.com/herceptin/physician/j_profile/pop_chart2.htm
“Significant improvements in one-year survival (secondary
study endpoint)”
- Improvements in One-Year Survival chart
http://www.herceptin.com/herceptin/physician/j_profile/pop_chart3.htm
“Efficacy in Monotherapy
Herceptin as a single agent was found to be effective in patients with
HER2 protein overexpressing metastatic breast cancer that had relapsed
following one or more chemotherapy regimens for their metastatic
disease.”
“Response With Monotherapy
The overall response rate (ORR) (complete response + partial
response), as determined by an independent Response Evaluation
Committee,* was 14%, with a 2% complete response rate and a 12%
partial response rate. Complete responses were observed only in
patients with disease limited to skin and lymph nodes.[1]
The median duration of response was 9.1 months, with a median survival
of 12.8 months (range 0.5 to 24+ months). Twenty-four percent of
patients were progression free at 5.8 months.[2]
The degree of HER2 protein overexpression was a predictor of treatment
effect, though both 2+ and 3+ patients showed benefit.”
Press Release
“Breast Cancer: Navelbine Plus Herceptin Promising For Metastatic
Breast Cancer”
http://www.pslgroup.com/dg/14fc7e.htm
“The study, sponsored by Genentech, Inc., the maker of Herceptin, was
conducted at Dana-Farber Cancer Institute in Boston to assess the
safety and efficacy of this combination.”
“To date, treatment has been well tolerated with neutropenia as the
only grade 3 or 4 toxicity reported (30 percent), and this has been
managed without growth factor support. Only one patient experienced
febrile neutropenia. Three patients experienced decreases in Ejection
Fraction (EF) greater than 15 percent and/or to less than 50 percent.
The overall response rate was 71 percent (24/34) of patients; all
partial responses (PR). Activity was reported regardless of prior
chemotherapy for metastatic disease (first-line PR = 77 percent,
second-line PR = 60 percent, and third-line PR = 83 percent). These
preliminary data suggest promising activity with favorable
tolerability between Navelbine and Herceptin in HER2 positive
metastatic breast cancer and warrant confirmation with further
studies.”
The university of Arizona are wanting to trial (Navelbine) Alone
Versus Vinorelbine (Navelbine) plus Trastuzumab (Herceptin) for
Patients with HER-2 Positive Metastatic Breast Cancer Who Have Failed
Previous Taxol/Taxotere/Trastuzumab (Herceptin) Combination Therapy,
no results published but gives an indication of other combinations.
Telemedicine.Arizona.edu
http://www.telemedicine.arizona.edu/bc/protocols.html
Tirgan.com
http://www.tirgan.com/herceptin.htm
“Combination of Herceptin and Taxol is a very effective regimen in
patients with metastatic breast cancer with response rates of about
40%” though there is no mention of detailed clinical trials.
PeerView Press “inBrief Trial Evaluates Herceptin for Treatment of
Early Stage Breast Cancer” by Ed Ungar
http://www.peerviewpress.com/peerview.nsf/release/_HER-SOTA2002-InBrief6.html
“MONTREUX, SWITZERLAND -- February 24, 2002 -- ....
Elizabeth Tan-Chiu, MD, NSABP associate director of medical oversight
and the trial's protocol officer, noted that in the pivotal trial that
led to the licensing of Herceptin for metastatic breast cancer,
doxorubicin/cyclophosphamide (AC) and Herceptin had a better response
rate than Herceptin plus paclitaxel. However, the latter combination
became the standard therapy due to a lower rate of cardiotoxicity.”
“Patients with early-stage breast cancer are more likely to tolerate
the combination of AC plus Herceptin because, unlike most metastatic
patients, these women are less likely to have been weakened by
repeated rounds of chemotherapy and "are in the prime of their lives
with not many co-morbidities", Dr. Tan-Chiu theorized.”
Prous.com “New combinations with Herceptin® in metastatic breast
cancer” by Eric Winer, Dana-Farber Cancer Institute, Boston,
Massachusetts, USA
http://www.prous.com/herceptin/abstracts/winer.html
“There is currently great interest in identifying novel therapeutic
regimens that employ Herceptin® in combination with other anticancer
agents in metastatic breast cancer. In the USA, Herceptin® plus
paclitaxel is the only Herceptin®-containing combination regimen that
has received FDA approval. However, a number of other regimens are
under active investigation, including combinations of Herceptin® with
vinorelbine, docetaxel, cisplatin, carboplatin or cisplatin and
docetaxel, and hormonal therapy. Clinical trials to evaluate combined
therapy consisting of Herceptin® plus taxanes are described elsewhere.
To date, of these combinations, the most extensive clinical experience
has been with Herceptin® plus vinorelbine. At Dana-Farber Partners
Cancer Care, we have completed a phase II trial of Herceptin® in
combination with vinorelbine in
40 patients with metastatic breast cancer and 2+ or 3+ HER2
overexpression by immunohistochemistry1 (Slide 2). A total of 82% of
patients had received prior chemotherapy, with 52% having received
chemotherapy in the metastatic setting. Patients were treated with
weekly standard-dose Herceptin® (4mg/kg initial dose followed by
2mg/kg) and weekly vinorelbine (25mg/m2) with dose reduction for
myelosuppression. To date, more than 1,000 weekly treatments have been
administered to the study population (range 1-68+ per patient) and
full-dose vinorelbine has been administered in 80% of weekly courses.
Combined Herceptin® plus vinorelbine therapy produced an overall
response rate of 75%, with response rates of 84% and 80% in first-line
patients and HER2 3+ patients, respectively (Slide 3). The predominant
toxicity associated with the regimen was myelosuppression; 28% of
patients experienced grade III granulocytopenia and 10% had grade IV
granulocytopenia. There were no grade III/IV non-haematological
toxicities attributable to the treatment. Based on these findings, a
larger multi-institutional study will be initiated in the summer of
2000. On the basis of both preclinical and completed trial data, there
is great interest in combination therapy that includes the platinum
analogues, cisplatin and carboplatin, and anthracyclines that produce
lower cardiotoxicity than doxorubicin”
Interaction between Herceptin® and taxanes by Véronique Diéras
Institut Curie, Service de Medecine Oncologique, Paris France
http://www.prous.com/herceptin/abstracts/dieras.html
“A phase II study examining weekly Herceptin® (4mg/kg initial dose
followed by 2mg/kg) plus weekly 1-hour paclitaxel (90mg/m2) in 94
HER2-positive and HER2-negative metastatic breast cancer patients
produced an overall response rate of 60% and a median duration of
response of 7 months1 (Slide 2). Response rates were analysed on the
basis of the HER2 testing method used to select patients
(immunohistochemistry or fluorescence in-situ hybridisation [FISH]).
Combined therapy produced a response rate of 75% in FISH-positive
patients and 48% in FISH-negative patients (p=0.01).”
“In addition, a US trial to evaluate weekly Herceptin® (4mg/kg initial
dose followed by 2mg/kg) plus weekly one-hour paclitaxel (80mg/m2) is
ongoing in 19 patients with metastatic breast cancer.2 The results to
date indicate a 16% complete response (CR), 11% partial response (PR),
58% stable disease, 11% progressive disease and 5% not evaluable.”
ESMO.org “Citation: Annals of Oncology”, Vol 11, Suppl.4 October 2000,
page 32 “Trastuzumab plus paclitaxel in the treatment of advanced
breast cancer: Single centre experience.”
http://www.esmo.org/reference/abstracts00/bc3/132.htm
“From the beginning of 1999 ten women with advanced HER2 positive (2+
or 3+) breast cancer, tested by immonohistochemistry (HerceptTest),
were treated with combination of trastuzumab (Herceptin) and
paclitaxel (Taxol).”
“Out of ten treated women six (60%) achieved partial response (PR), 2
(20%)stable disease (SD) and 2 (20%) had disease progression. We
documented overall response (SD+PR) in 8 patients (80%). One year
survival probability is 70%, while disease progression free survival
is 20%. In a period of 6 months after the termination of therapy all 8
patients who had achieved PR and SD, have progressed. Brain metastasis
were documented in 5 patients, liver in 2 and pulmonary metastasis in
1 patient.”
Annals of Oncology “Cooperative inhibitory effect of ZD1839 (Iressa)
in combination with trastuzumab (Herceptin) on human breast cancer
cell growth”
http://annonc.oupjournals.org/cgi/content/full/13/1/65?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&titleabstract=Cooperative+Inhibitory+Effect&searchid=1031170869450_421&stored_search=&FIRSTINDEX=0&tdate=2/28/2002&journalcode=annonc
An ‘alternative’ treatment called CAAT (Controlled Amino Acid Therapy)
claims to help and be combined with chemotherapy.
An excerpt from A.P. John Institute
( http://www.apjohncancerinstitute.org/case.htm )
“Marilyn P. 64 Years
Condition and treatment: After being diagnosed with recurrent breast
cancer, Marilyn’s cancer had metastasized to both lungs. She enrolled
in CAAT for eight months while continuing with chemotherapy treatment.
Results: The tumor in Marilyn’s left lung totally disappeared. A small
tumor .5 cm was removed from her right lung.”
Categorized cancer research studies and references which together
support the biological activities of CAAT
http://www.apjohncancerinstitute.org/cancerresearch.htm
About CAAT from the Institute’s site
http://www.apjohncancerinstitute.org/caat.htm
“Basically, CAAT is an amino acid and carbohydrate deprivation
protocol using scientifically formulated amino acids. Research by
Dr.Marco Rabinowitz of the National Cancer Institute and Dr. Dr.
Albert B. Lorincz of the University of Chicago shows how beneficial
amino acid deprivation therapy can be in treating cancer.
CAAT also includes a low carbohydrate regimen that is personalized for
each patient. Dr. Chi Van Dang of the Johns Hopkins School of Medicine
reported that cancer cells are such sugar junkies that glucose
deprivation can contribute significantly to their demise.
...Because its activity is so basic, it does not interfere with
conventional therapies but rather complements and enhances their
effectiveness. CAAT combined with chemotherapy or acting alone, has
stopped tumor growth, reduced tumor size, or eliminated tumors while
improving one’s quality of life.”
Useful Links:
Prous.com “Optimising the Role of Herceptin in Breast Cancer”
http://www.prous.com/herceptin/program.html
Annals of Oncology site search
http://www.annonc.oupjournals.org/search.dtl
Herceptin site
http://www.herceptin.com
FDA.gov “Breast Cancer: Better Treatments Save More Lives” by Carol
Lewis
http://www.fda.gov/fdac/features/1999/499_breast.html
Aneas.net “Women Health” - All Breast Cancer Resources
http://aneas.net/womenhealth/breast_cancer_resources.asp
Search Strategy:
metastatic Herceptin treatment breast cancer
://www.google.com/search?hl=en&lr=&ie=ISO-8859-1&newwindow=1&q=metastatic+Herceptin+treatment+breast+cancer
successfully treating metastasized breast cancer
://www.google.com/search?q=successfully+treating+metastasized+breast+cancer&hl=en&lr=&ie=UTF-8&newwindow=1&start=20&sa=N
combination breast cancer herceptin
://www.google.com/search?hl=en&lr=&ie=ISO-8859-1&newwindow=1&q=combination+breast+cancer+herceptin+
As Herceptin is a fairly new drug, the amount and depth of research is
not as extensive as it might be for a more proven drug, though I hope
what information I have managed to locate is useful in someway,
and that the oncologist recommends a suitable combination for your
friend.
If you need a clarification to the answer, just ask.
(though bear in mind, as a researcher I can only seek information and
not give professional advice)
kind regards
lot-ga |
