Journal of Clinical Oncology, Vol 20, Issue 5
(March), 2002: 1215-1221
© 2002 American Society for Clinical Oncology
Cardiac Dysfunction in the Trastuzumab Clinical Trials Experience
By Andrew Seidman,
Clifford Hudis,
Mary Kathryn Pierri,
Steven Shak,
Virginia Paton,
Mark Ashby,
Maureen Murphy,
Stanford J. Stewart,
Deborah Keefe
From the Memorial Sloan-Kettering Cancer Center, New York, NY; and Genentech Inc, South San Francisco, CA.
Address reprint requests to Andrew Seidman, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; email: seidmana{at}mskcc.org
 |
ABSTRACT
|
|---|
PURPOSE: This study sought to estimate cardiac dysfunction (CD) risk for patients receiving trastuzumab; to characterize observed CD by severity, treatment, and clinical outcome; to assess effects of baseline clinical risk factors on CD; and to assess effects of cumulative doses of anthracyclines and trastuzumab on CD.
PATIENTS AND METHODS: A retrospective review of records for patients enrolled onto any of seven phase II and III trastuzumab clinical trials was performed. Predefined criteria were used for the diagnosis, and the New York Heart Association functional classification system was used to document CD severity. Product-limit estimates were used to summarize the cumulative anthracycline and trastuzumab doses at the time of CD onset.
RESULTS: Patients treated with trastuzumab were found to be at an increased risk for CD. The incidence was greatest in patients receiving concomitant trastuzumab and anthracycline plus cyclophosphamide (27%). The risk was substantially lower in patients receiving paclitaxel and trastuzumab (13%) or trastuzumab alone (3% to 7%); however, most of these patients had received prior anthracycline therapy. CD was noted in 8% of patients receiving anthracycline plus cyclophosphamide and 1% receiving paclitaxel alone. Most trastuzumab-treated patients developing CD were symptomatic (75%), and most improved with standard treatment for congestive heart failure (79%).
CONCLUSION: Trastuzumab is associated with an increased risk of CD, which is greatest in patients receiving concurrent anthracyclines. In most patients with metastatic breast cancer, the risk of CD can be justified given the improvement in overall survival previously reported with trastuzumab.
|
INTRODUCTION
|
|---|
Trastuzumab (Herceptin; Genentech Inc, South San Francisco, CA) is a humanized monoclonal antibody approved by the United States Food and Drug Administration in September 1998 for the treatment of women with metastatic breast cancer whose tumors overexpress p185HER2. HER2, also known as c-erbB-2 or neu, is a proto-oncogene that codes for p185HER2. This protein is a transmembrane receptor tyrosine kinase that is a member of the epidermal growth factor family. The HER2 gene is amplified and the p185HER2 protein overexpressed in 20% to 25% of human breast cancers.1 Patients with tumors demonstrating this alteration have a poor prognosis.1,2
Trastuzumab is indicated in combination with paclitaxel for first-line treatment and as a single agent for second- or third-line treatment of metastatic breast cancer. When used in combination with chemotherapy in the first-line treatment of metastatic breast cancer, trastuzumab improves response rate, response duration, time to progression, time to treatment failure,3 and median overall survival4 compared with treatment with chemotherapy alone. Single-agent trastuzumab produces durable objective responses in patients whose tumors previously failed to respond to one or more chemotherapies for metastatic disease.5
During the course of the trastuzumab pivotal trials, cardiac dysfunction (CD) similar to that previously described in patients treated with anthracyclines was observed in women treated with trastuzumab. Because of this observation, a number of changes were instituted in the trials, in particular the establishment of an independent Cardiac Review and Evaluation Committee (CREC). The CREC was established to obtain independent and unbiased estimates of CD risk for patients receiving trastuzumab; to characterize the observed CD by severity, treatment, and clinical outcome; to assess the effects of baseline clinical risk factors on CD risk; and to assess the effects of cumulative doses of doxorubicin, epirubicin, and trastuzumab on CD risk. This report details the findings of the CREC and describes the syndrome of CD associated with the administration of trastuzumab.
|
PATIENTS AND METHODS
|
|---|
Patient Selection and Event Definition
Members of the CREC were Andrew D. Seidman, MD, Clifford A. Hudis, MD, and Deborah L. Keefe, MD, all of Memorial Sloan-Kettering Cancer Center, New York. Study patients reviewed by the CREC were identified through any one of several mechanisms, including the following: (1) independent CREC screening of the clinical trials database by means of broad search criteria for signs and symptoms of CD; (2) adverse event reporting (serious or nonserious) suggestive of CD; (3) review of the drug safety and clinical trials databases by means of search criteria appropriate for CD (including concomitant medications that might be used in the treatment of heart failure); and (4) review of cardiac left ventricular ejection fraction (LVEF) data for low absolute values (< 50%) or significant decreases (> 20% relative to baseline). Medical records for patients identified by the above processes were obtained and provided to the CREC for review. If medical records were not available, data collected from the clinical trials were provided. All identifying features of therapy were removed from records provided to the CREC. The CREC reviewed all information while remaining blinded to treatment assignment.
The CREC established the following criteria to confirm or revise a preliminary diagnosis of CD: (1) cardiomyopathy characterized by a decrease in cardiac LVEF that was either global or more severe in the septum; (2) symptoms of congestive heart failure (CHF); (3) associated signs of CHF, including but not limited to S3 gallop, tachycardia, or both; and (4) decline in LVEF of at least 5% to less than 55% with accompanying signs or symptoms of CHF, or a decline in LVEF of at least 10% to below 55% without accompanying signs or symptoms. Any one of the four criteria was sufficient to confirm a diagnosis of CD. Events were also categorized by means of the New York Heart Association (NYHA) functional classification system.6 In the NYHA system, patients are assigned to one of four functional classes on the basis of the degree of effort required to elicit symptoms of heart failure. Patients are classified as having symptoms at rest (class IV), at less than ordinary exertion (class III), with ordinary exertion (class II), and only at levels that would produce symptoms in normal people (class I). Data were collected until the trastuzumab pivotal trials were closed in mid-1999.
Statistical Considerations
CREC determined diagnoses, assessed cardiac function at time of presentation, and summarized the management of CD, changes in NYHA class, and cardiac outcomes in all patients with CD. These data were summarized for seven different antineoplastic regimens (Table 1).
Data regarding potential risk factors for CD were collected from the databases of the clinical trials. Major risk factors were total cumulative anthracycline dose, the presence of underlying cardiovascular disease (including hypertension), radiation to the left chest or mediastinum, and increasing age. For patients in the comparative chemotherapy pivotal trial, H0648g, product-limit estimates7 summarizing the distribution of cumulative anthracycline and trastuzumab doses at the time of onset of CD were calculated. The cumulative anthracycline dose was defined as the sum of the total doxorubicin administered before the study plus the total administered during the study, up to the date of CREC-defined onset of signs and symptoms or to the date of last patient contact. Similar definitions were used for cumulative trastuzumab doses.
Cumulative trastuzumab and doxorubicin exposure was summarized by disease response status and antineoplastic therapy for patients in study H0648g. Overall response rate and time to disease progression were summarized by CD status and antineoplastic therapy.
|
RESULTS
|
|---|
The CREC screens were applied to 1,219 patient records, 202 of which were identified for detailed review. CREC determined that 112 of these patients experienced CD, 83 patients had clinical manifestations with explanations other than CD, and seven patients were not assessable. When conditions other than CD were cited in the CREC reviewed materials, they included pericardial tamponade, cardiac arrhythmia, malignant pleural effusion, cardiac ischemia, cardiac arrest, and sepsis, which, by careful review, were thought to be unrelated to cancer treatment.
Table 2 summarizes the results of the CREC review by study and treatment regimen. Patients in study H0659g are a subset of patients from study H0648g who elected to participate in an extension study that provided an opportunity to receive trastuzumab alone or with chemotherapy, as directed by the treating physician. CD designations were made only for the study in which the event first occurred. This process limited to some degree the conclusions that could be drawn regarding the risks associated with any particular treatment group.
The experience in the pivotal comparative chemotherapy trial, H0648g, is particularly noteworthy. In this trial, patients treated with concurrent anthracyclines and trastuzumab experienced CD at a rate of 27% compared with a rate of 8% in patients treated with the anthracycline combination alone. An increased incidence of CD was also seen in patients treated with paclitaxel plus trastuzumab versus those treated with paclitaxel alone (13% compared with 1%, respectively).
CD was also observed in trials in which patients were treated with trastuzumab as a single agent or in combination with a variety of chemotherapeutic regimens. In the H0650g trial, patients were treated with trastuzumab as a single agent as the first therapy for metastatic disease. The observed rate of CD was 3%. In the H0649g trial, patients were treated with trastuzumab as a single agent as the second or third treatment for metastatic disease. The observed rate of CD in this trial was 5%.
Most patients who developed CD presented with symptoms (83 of 110 patients had their symptom status noted). Eight-two of these 83 patients received treatment for CHF. Treatments included diuretics (in 78% of treated patients), angiotensin-converting enzyme inhibitors (in 58% of patients), cardiac glycosides (in 58% of patients), and other inotropic agents (in 10% of patients). Other treatments reported included beta blockers, nitrates, and supplemental oxygen. Most patients received multiple treatments. When asked to assess response to initial therapy, the CREC concluded that the majority of patients (79%) improved with treatment.
It is of note that clinical presentation and treatment outcome differed markedly in patients presenting with CD in the trastuzumab and anthracycline plus cyclophosphamide (AC) and the trastuzumab plus paclitaxel subgroups of H0648g. Sixty-four percent of patients treated with concurrent trastuzumab plus AC presented with significant functional impairment (NYHA class III or IV), whereas only 20% of patients treated with trastuzumab plus paclitaxel presented with significant functional impairment (all class III). Eight of thirty-nine patients treated with trastuzumab plus AC continued to exhibit significant functional impairment (NYHA class III) after treatment, whereas none of 12 patients treated with trastuzumab plus paclitaxel exhibited significant functional impairment after treatment. In the heavily pretreated patients who received trastuzumab as a single agent (studies H0649g and H0551g), less impressive improvement in functional status was noted. This refractoriness to therapy might have related to more advanced disease, reduced functional capacity, and rigorous prior therapies. The relationship between treatment regimen, clinical presentation, and treatment outcome in patients presenting with CD is provided in Table 3 for patients who had both pretreatment and posttreatment evaluations.
View this table:
[in this window]
[in a new window]
|
Table 3. NYHA Functional Classification of CD Cases Before and After Treatment for Dysfunction: Selected Antineoplastic Regimens*
|
|
In the entire trastuzumab developmental clinical trials experience of 1,219 patients, 10 heart-related deaths were reported. Nine of the 10 were in patients who had received trastuzumab in the clinical trials. Analysis of potential risk factors associated with trastuzumab-associated CD was performed. Table 4 demonstrates that of suspected factors, only age had a statistically significant effect on CD risk and reached statistical significance only in the trastuzumab plus AC subgroup.
The relationship of CD risk to cumulative anthracycline exposure was investigated for patients in the pivotal H0648g study. Among patients in the trastuzumab plus AC subgroup, the cumulative dysfunction risk began to increase with doxorubicin exposure of approximately 300 mg/m2 (Fig 1). The product-limit estimate demonstrated a dramatic increase in risk at 360 mg/m2, but this effect was largely an artifact of the large fraction of patients who discontinued AC therapy after receiving six cycles of doxorubicin (per study protocol) and subsequently experienced CD. Approximately 60% of patients in both the trastuzumab plus AC and the AC alone subgroups discontinued AC therapy after six cycles. Because relatively few events occurred at cumulative doxorubicin doses less than 300 mg/m2, this trial provides limited information about CD risk below this exposure level.
View larger version (19K):
[in this window]
[in a new window]
|
Fig 1. Product-limit estimates of cumulative doxorubicin dose to CD onset. CREC-diagnosed CD (nonassessable patients excluded) for study H0648g.
|
|
In study H0648g, the curve representing cumulative CD risk in patients receiving trastuzumab plus AC was similar in shape to that of patients receiving AC alone; however, the risk function was shifted to the left, indicating a greater risk in the trastuzumab plus AC subgroup. The magnitude of the shift suggests that trastuzumab may increase the risk of CD by a degree equivalent to approximately 100 mg/m2 of doxorubicin exposure. Product-line estimates assume that a patient whose data has been censored has a nonzero risk after censoring equal to that of a patient remaining at risk. The product-limit estimates can be expected to overestimate the true CD risk because patients whose data have been censored on average received lower cumulative doses of chemotherapy and trastuzumab, and their risk is likely to be less informative than the relative positions of the two curves, indicating that trastuzumab increases the risk of CD more than that induced by treatment with anthracyclines alone.
An exploratory analysis was conducted to evaluate the overall benefit of trastuzumab therapy to patients with metastatic breast cancer.8 Time to treatment failure was defined as the time to progressive disease or CD, whichever occurred first. We found that trastuzumab-containing regimens produced an improvement in time to treatment failure compared with regimens that did not include trastuzumab (Table 5). A similar difference was observed in each of the treatment substrata. CD-free survival, defined as the time to symptomatic CHF (NYHA functional class III or IV) or death, followed a similar pattern, with longer survival noted in trastuzumab-treated groups.8
|
DISCUSSION
|
|---|
This article details the unexpected observation of increased rates of CD in the trastuzumab clinical trials program and the steps that were taken to document and characterize the course of the observed syndrome. CHF was detected as a safety signal late in the development of the drug. Although CHF was seen in some patients participating in phase II trials, the rate of occurrence was sufficiently low and patients at sufficiently increased risk because of anthracycline pre-exposure that the increased risk with trastuzumab treatment was not appreciated. Concomitant use of anthracyclines and trastuzumab had not been used in the phase II program that focused on single-agent therapy and the interaction of trastuzumab with cisplatin. Therefore, it was not until the occurrence of several cases in the pivotal phase III combination chemotherapy trial that a safety signal was detected. It was soon recognized that the syndrome of trastuzumab-associated CD resembled the cardiomyopathy associated with previously described anthracycline cardiotoxicity9,10 and that the rates of occurrence were greatest when trastuzumab was used concomitantly with anthracyclines.
Caution should be exercised in interpreting the results of the CREC experience detailed here. After detection of the safety signal, several communications to the trial investigators detailed concerns related to the use of trastuzumab in this open-label trial. These might have resulted in biased overreporting of cardiac events in the trastuzumab-containing subgroups within the trial.11 Furthermore, although the CREC was established to provide independent analysis of the events observed, the results are necessarily limited by the retrospective nature of the analysis. Finally, the conservative criteria applied by CREC to confirm or revise a preliminary diagnosis of CD to include "an absolute decline in left ventricular ejection fraction of at least 5% to below 55%" could conceivably have biased the analysis toward overestimation of the incidence of CD.
The pathophysiologic basis of trastuzumab-associated CD is poorly understood. Four endomyocardial biopsies obtained during the conduct of the trials failed to clarify this issue (data not provided). One biopsy was consistent with anthracycline toxicity, and a second had mild changes consistent with anthracycline-induced myocyte damage. However, two specimens did not demonstrate changes consistent with anthracycline damage and also had no evidence of inflammation, necrosis, or fibrosis. Immunohistochemical staining from p185HER2 was consistently negative in the specimens. Two of four specimens were positive for HER2 mRNA by in situ hybridization, but only three of four specimens demonstrated control binding of an actin probe. It remains unknown whether trastuzumab exacerbates previous damage caused by anthracyclines or acts through an independent mechanism to directly affect the cardiac myocyte.
It has been suggested that p185HER2 may play a role in myocyte survival.12 However, the molecular mechanisms underlying trastuzumab-associated cardiomyopathy are obscure. Knockout of the c-erbB-2 gene results in embryonic lethality in mice and is associated with profound developmental defects in the heart and central nervous systems.13 Recent discovery of the association of p185HER2 with gp130 and gp130-inducible myocyte survival pathways14 suggests that identification of myocyte survival factors could lead to new therapeutic approaches for this and other cardiomyopathies.15
Risk factors for trastuzumab-associated CD are poorly delineated. Only age was associated with increased risk, and only in the AC substratum. A better understanding of risk factors is needed. Multigated blood pool imaging of the heart (MUGA scanning) is currently recommended for baseline assessment and on-treatment evaluation of trastuzumab-treated patients. MUGA scanning seems unable to identify early evidence of CD, and once impaired systolic function is detected by MUGA, significant cardiac damage has already occurred. It would be optimal to have a sensitive, noninvasive test to detect minor cardiac damage in time for an intervention to preserve myocardium. Troponin-T16 and pro-BNP17 levels are being examined in clinical trials to define their utility in detecting early myocardial damage. In addition, echocardiography is being compared with MUGA scanning to determine if this modality might be more sensitive to changes associated with trastuzumab exposure.
In the phase III pivotal trial, all patients had been or were exposed to anthracyclines, the paclitaxel substratum having received anthracyclines in the adjuvant setting and anthracycline-naive patients entering the AC substratum receiving anthracyclines during the trial by protocol design. We found incidence rates for development of CD to be greatest when trastuzumab and anthracyclines are used concomitantly. Although epirubicin was used much less frequently in these studies than doxorubicin, the incidence of cardiac toxicity seemed to be similar regardless of the anthracycline used. Rates of CD seem substantially lower and the syndrome less severe when the use of trastuzumab is temporally separated from anthracycline exposure, as demonstrated by the rates in the trastuzumab treatment arm of the paclitaxel substratum and rates in the single-agent trials. Results in other clinical trials with prospective frequent monitoring of left ventricular function have suggested that the safety profile of concomitant treatment of patients with trastuzumab and weekly paclitaxel is acceptable.18
Observations of CD in the trastuzumab pivotal trials and the experience with trastuzumab and weekly paclitaxel have influenced the design of trastuzumab adjuvant trials undertaken recently by the major United States cooperative groups. The National Surgical Adjuvant Breast and Bowel Project B-31 trial has been designed with a formal safety evaluation phase and an efficacy evaluation phase. The first 1,000 patients entered onto the trial will participate in a meticulous evaluation of cardiac safety. Patients will undergo baseline and critical time MUGA scanning through the course of treatment with AC for four cycles, then paclitaxel for four cycles with or without trastuzumab for 1 year. The United States Intergroup trial uses similar monitoring as patients receive AC for four cycles, then paclitaxel weekly for 12 weeks without, with, or followed by trastuzumab for 1 year. Neither trial uses concomitant use of trastuzumab and anthracyclines, and the Intergroup trial examines the importance of further temporal separation of trastuzumab administration from anthracycline administration.
Trastuzumab is an important new treatment for women with breast cancers that overexpress the HER2 protein; it is one of only a few drugs that has produced a survival advantage for patients with metastatic disease. The noteworthy efficacy of trastuzumab has been detailed elsewhere.3-5 In this report, we detail the experience with the major side effect noted in the trastuzumab clinical trials: CD. Patients treated with trastuzumab seem to be at increased risk for the development of a cardiomyopathy reminiscent of the cardiomyopathy associated with anthracyclines. All clinical trials reviewed by CREC were conducted on a background of anthracycline exposure because anthracyclines are the foundation of many adjuvant treatments for early-stage breast cancer, and anthracyclines are believed to be of special importance in the treatment of HER2-positive breast cancer.19,20 The greatest risk for development of CD was seen in patients receiving concomitant trastuzumab and anthracycline. Risks for patients treated with concurrent paclitaxel and trastuzumab and patients treated with trastuzumab as a single agent seem to be substantially lower than those associated with the concurrent administration of anthracycline and trastuzumab. The risk in anthracycline-naive patients is not well defined but is apparently greater than zero because at least one patient with preexisting cardiac disease in the H0650g study experienced CD during the trial.
As with all decisions in clinical medicine, the decision to use trastuzumab involves an analysis of risk and benefit. The risk of CD associated with the use of trastuzumab can usually be justified, given the 25% improvement in overall survival associated with the use of trastuzumab in the pivotal comparative chemotherapy trial, H0648g.5 Trastuzumab provided improved time to treatment failure in this study, an end point that incorporates time to progressive disease or cardiac event. This conclusion of benefit is further bolstered by the poor prognosis associated with HER2-positive breast cancer and the likelihood of functional improvement with appropriate treatment of the CD.
Because of the important antitumor activity of trastuzumab when combined with doxorubicin and cyclophosphamide, strategies to prevent or limit cardiotoxicity are being investigated. Clinical trials that use liposomal anthracyclines as well as the cardioprotective agent dexrazoxane in combination with trastuzumab are ongoing. For example, TLC D-99, a liposomal doxorubicin formulation with less cardiotoxicity than conventional doxorubicin, has been preliminarily indicated to be well tolerated and to have good antitumor efficacy in patients with HER2-positive tumors treated with TLC D-99 in combination with trastuzumab. In this phase I/II study, no cardiotoxicity was reported in 20 women with locally advanced or metastatic breast cancer.21
Important goals of future trastuzumab trials should be the identification of risk factors for CD, as well as identification of appropriate strategies for prevention or treatment of CD. It is likely that meeting these goals will require a better understanding of the molecular mechanisms of trastuzumab action on the myocardial cell.
|
REFERENCES
|
|---|
1.
Slamon DJ, Clark GM, Wong SG, et al: Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235: 177-182, 1987[Abstract/Free Full Text]
2.
Ravdin PM, Chamness GC: The c-erbB-2 proto-oncogene as a prognostic and predictive marker in breast cancer: A paradigm for the development of other macromolecular markers—A review. Gene 159: 19-27, 1995[CrossRef][Medline]
3.
Slamon DJ, Leyland-Jones B, Shak S, et al: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344: 783-792, 2001[Abstract/Free Full Text]
4.
Norton L, Slamon D, Leyland-Jones B, et al: Overall survival (OS) advantage to simultaneous chemotherapy (CRx) plus the humanized anti-HER2 monoclonal antibody Herceptin (H) in HER2-overexpressing (HER2+) metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 18: 127a, 1999 (abstr 483)
5.
Cobleigh MA, Vogel CL, Tripathy D, et al: Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17: 2639-2648, 1999[Abstract/Free Full Text]
6.
Criteria Committee of the NYHA: Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels (ed 7). Boston, MA, Little, Brown, 1973
7.
Cox DR: Regression models and life-tables. J R Stat Soc B 34: 187-220, 1972
8.
Tripathy D, Seidman A, Hudis C, et al: Effect of cardiac dysfunction on treatment outcome in the trastuzumab (Herceptin) pivotal trial. Proc Am Soc Clin Oncol 20: 49a, 2001 (abstr 191)
9.
Billingham ME, Mason JW, Bristow MR, et al: Anthracycline cardiomyopathy monitored by morphologic changes. Cancer Treat Rep 62: 865-872, 1978[Medline]
10.
Singal PK, Iliskovic N: Doxorubicin-induced cardiomyopathy. N Engl J Med 339: 900-905, 1998[Free Full Text]
11.
Ewer MS, Gibbs HR, Swafford J, et al: Cardiotoxicity in patients receiving trastuzumab (Herceptin): Primary toxicity, synergistic or sequential stress, or surveillance artifact? Semin Oncol 26: 96-101, 1999[Medline]
12.
Chien KR: Stress pathways and heart failure. Cell 98: 555-558, 1999[CrossRef][Medline]
13.
Lee K-F, Simon H, Chen H, et al: Requirement for neuregulin receptor erbB2 in neural and cardiac development. Nature 378: 394-398, 1995 (letter)[CrossRef][Medline]
14.
Hirota H, Chen J, Betz UA, et al: Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress. Cell 97: 189-198, 1999[CrossRef][Medline]
15.
Chien KR: Genomic circuits and the integrative biology of cardiac diseases. Nature 407: 227-232, 2000[CrossRef][Medline]
16.
Chapelle JP: Cardiac troponin I and troponin T: Recent players in the field of myocardial markers. Clin Chem Lab Med 37: 11-20, 1999[CrossRef][Medline]
17.
Cowie MR, Struthers AD, Wood DA, et al: Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care. Lancet 350: 1349-1353, 1997[CrossRef][Medline]
18.
Seidman AD, Fornier MN, Esteva FJ, et al: Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol 19: 2587-2595, 2001[Abstract/Free Full Text]
19.
Muss HB, Thor AD, Berry DA, et al: c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med 330: 1260-1266, 1994[Abstract/Free Full Text]
20.
Thor AD, Berry DA, Budman DR, et al: erbB-2, p53, and efficacy of adjuvant therapy in lymph node–positive breast cancer. J Natl Cancer Inst 90: 1346-1360, 1998[Abstract/Free Full Text]
21.
Theodoulou M, Campos S, Welles G, et al: Preliminary cardiac safety and efficacy data from a phase I/II trial of TLC D-99 (D-99) and trastuzumab (T) in patients (pts) with locally advanced or metastatic breast cancer (LABC/MBC). Proc Am Soc Clin Oncol 20: 46a, 2001 (abstr 180)
Submitted November 27, 2000;
accepted November 2, 2001.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Facebook  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
F. G. VAN ROOIJ, L. D.A. DORRESTEIJN, M. M.J.A. VAN BOKHOVEN, and C. C.P. VERSTAPPEN
A Throbbing Pain in the Head: Trastuzumab-induced Migraine
Anticancer Res,
October 1, 2009;
29(10):
4223 - 4225.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Di Lorenzo, R. Autorino, G. Bruni, G. Carteni, E. Ricevuto, M. Tudini, C. Ficorella, C. Romano, M. Aieta, A. Giordano, et al.
Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis
Ann. Onc.,
September 1, 2009;
20(9):
1535 - 1542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. T.H. Yeh and C. L. Bickford
Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management.
J. Am. Coll. Cardiol.,
June 16, 2009;
53(24):
2231 - 2247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. C. Benavides, J. D. Gates, M. G. Carmichael, R. Patel, J. P. Holmes, M. T. Hueman, E. A. Mittendorf, D. Craig, A. Stojadinovic, S. Ponniah, et al.
The Impact of HER2/neu Expression Level on Response to the E75 Vaccine: From U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02
Clin. Cancer Res.,
April 15, 2009;
15(8):
2895 - 2904.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Barros Costa
Review Article: Targeted Therapy: Comprehensive Review
American Journal of Hospice and Palliative Medicine,
April 1, 2009;
26(2):
137 - 146.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K.-K. Wong, P. M. Fracasso, R. M. Bukowski, T. J. Lynch, P. N. Munster, G. I. Shapiro, P. A. Janne, J. P. Eder, M. J. Naughton, M. J. Ellis, et al.
A Phase I Study with Neratinib (HKI-272), an Irreversible Pan ErbB Receptor Tyrosine Kinase Inhibitor, in Patients with Solid Tumors
Clin. Cancer Res.,
April 1, 2009;
15(7):
2552 - 2558.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Y. Wonders and B. S. Reigle
Trastuzumab and Doxorubicin-Related Cardiotoxicity and the Cardioprotective Role of Exercise
Integr Cancer Ther,
March 1, 2009;
8(1):
17 - 21.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. Cortes, S. Di Cosimo, M. A. Climent, H. Cortes-Funes, A. Lluch, P. Gascon, J. I. Mayordomo, M. Gil, M. Benavides, L. Cirera, et al.
Nonpegylated Liposomal Doxorubicin (TLC-D99), Paclitaxel, and Trastuzumab in HER-2-Overexpressing Breast Cancer: A Multicenter Phase I/II Study
Clin. Cancer Res.,
January 1, 2009;
15(1):
307 - 314.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G. Morris, H. L. McArthur, C. T. Dang, and C. A. Hudis
Selection of Appropriate Patients for Anthracycline Therapy
ASCO Educational Book,
January 1, 2009;
2009(1):
11 - 18.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Martin, F. J. Esteva, E. Alba, B. Khandheria, L. Perez-Isla, J. A. Garcia-Saenz, A. Marquez, P. Sengupta, and J. Zamorano
Minimizing Cardiotoxicity While Optimizing Treatment Efficacy with Trastuzumab: Review and Expert Recommendations
Oncologist,
January 1, 2009;
14(1):
1 - 11.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Lenihan and F. J. Esteva
Multidisciplinary Strategy for Managing Cardiovascular Risks When Treating Patients with Early Breast Cancer
Oncologist,
December 1, 2008;
13(12):
1224 - 1234.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Rayson, D. Richel, S. Chia, C. Jackisch, S. van der Vegt, and T. Suter
Anthracycline-trastuzumab regimens for HER2/neu-overexpressing breast cancer: current experience and future strategies
Ann. Onc.,
September 1, 2008;
19(9):
1530 - 1539.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. L. Gomez, D. C. Doval, M. A. Chavez, P. C.-S. Ang, Z. Aziz, S. Nag, C. Ng, S. X. Franco, L. W.C. Chow, M. C. Arbushites, et al.
Efficacy and Safety of Lapatinib As First-Line Therapy for ErbB2-Amplified Locally Advanced or Metastatic Breast Cancer
J. Clin. Oncol.,
June 20, 2008;
26(18):
2999 - 3005.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Burstein, A. M. Storniolo, S. Franco, J. Forster, S. Stein, S. Rubin, V. M. Salazar, and K. L. Blackwell
A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer
Ann. Onc.,
June 1, 2008;
19(6):
1068 - 1074.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Belkacemi, J. Gligorov, M. Ozsahin, H. Marsiglia, B. De Lafontan, H. Laharie-Mineur, L. Aimard, E.-C. Antoine, B. Cutuli, M. Namer, et al.
Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study
Ann. Onc.,
June 1, 2008;
19(6):
1110 - 1116.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. A. Perez, M. Koehler, J. Byrne, A. J. Preston, E. Rappold, and M. S. Ewer
Cardiac Safety of Lapatinib: Pooled Analysis of 3689 Patients Enrolled in Clinical Trials
Mayo Clin. Proc.,
June 1, 2008;
83(6):
679 - 686.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. L. Frei and S. A. Soefje
A Review of the Cardiovascular Effects of Oncology Agents
Journal of Pharmacy Practice,
April 1, 2008;
21(2):
146 - 158.
[Abstract]
[PDF]
|
|
|
|
|
|
|
E. A. Perez, V. J. Suman, N. E. Davidson, G. W. Sledge, P. A. Kaufman, C. A. Hudis, S. Martino, J. R. Gralow, S. R. Dakhil, J. N. Ingle, et al.
Cardiac Safety Analysis of Doxorubicin and Cyclophosphamide Followed by Paclitaxel With or Without Trastuzumab in the North Central Cancer Treatment Group N9831 Adjuvant Breast Cancer Trial
J. Clin. Oncol.,
March 10, 2008;
26(8):
1231 - 1238.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. P. Sengupta, D. W. Northfelt, F. Gentile, J. L. Zamorano, and B. K. Khandheria
Trastuzumab-Induced Cardiotoxicity: Heart Failure at the Crossroads
Mayo Clin. Proc.,
February 1, 2008;
83(2):
197 - 203.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ramond, E. Sartorius, M. Mousseau, C. Ribuot, and M. Joyeux-Faure
Erythropoietin Pretreatment Protects Against Acute Chemotherapy Toxicity in Isolated Rat Hearts
Experimental Biology and Medicine,
January 1, 2008;
233(1):
76 - 83.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. R.J. H. Bird and S. M. Swain
Cardiac Toxicity in Breast Cancer Survivors: Review of Potential Cardiac Problems
Clin. Cancer Res.,
January 1, 2008;
14(1):
14 - 24.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Widakowich, G. de Castro Jr., E. de Azambuja, P. Dinh, and A. Awada
Review: Side Effects of Approved Molecular Targeted Therapies in Solid Cancers
Oncologist,
December 1, 2007;
12(12):
1443 - 1455.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Li, Q. Pan, W. Han, Z. Liu, L. Li, and X. Hu
Schisandrin B Prevents Doxorubicin-Induced Cardiotoxicity via Enhancing Glutathione Redox Cycling
Clin. Cancer Res.,
November 15, 2007;
13(22):
6753 - 6760.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Kumar, T. P. Quinn, and S. L. Deutscher
Evaluation of an 111In-Radiolabeled Peptide as a Targeting and Imaging Agent for ErbB-2 Receptor Expressing Breast Carcinomas
Clin. Cancer Res.,
October 15, 2007;
13(20):
6070 - 6079.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Carver, C. L. Shapiro, A. Ng, L. Jacobs, C. Schwartz, K. S. Virgo, K. L. Hagerty, M. R. Somerfield, D. J. Vaughn, and for the ASCO Cancer Survivorship Expert Panel
American Society of Clinical Oncology Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors: Cardiac and Pulmonary Late Effects
J. Clin. Oncol.,
September 1, 2007;
25(25):
3991 - 4008.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Lemmens, K. Doggen, and G. W. De Keulenaer
Role of Neuregulin-1/ErbB Signaling in Cardiovascular Physiology and Disease: Implications for Therapy of Heart Failure
Circulation,
August 21, 2007;
116(8):
954 - 960.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-A. Pearson, C. L. Ringland, and R. L. Ward
Trastuzumab and Metastatic Breast Cancer: Trastuzumab Use in Australia Monitoring the Effect of an Expensive Medicine Access Program
J. Clin. Oncol.,
August 20, 2007;
25(24):
3688 - 3693.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Telli, S. A. Hunt, R. W. Carlson, and A. E. Guardino
Trastuzumab-Related Cardiotoxicity: Calling Into Question the Concept of Reversibility
J. Clin. Oncol.,
August 10, 2007;
25(23):
3525 - 3533.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S Beauclair, P Formento, J. Fischel, W Lescaut, R Largillier, E Chamorey, P Hofman, J. Ferrero, G Pages, and G Milano
Role of the HER2 [Ile655Val] genetic polymorphism in tumorogenesis and in the risk of trastuzumab-related cardiotoxicity
Ann. Onc.,
August 1, 2007;
18(8):
1335 - 1341.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. R. Correa, H. I. Litt, W.-T. Hwang, V. A. Ferrari, L. J. Solin, and E. E. Harris
Coronary Artery Findings After Left-Sided Compared With Right-Sided Radiation Treatment for Early-Stage Breast Cancer
J. Clin. Oncol.,
July 20, 2007;
25(21):
3031 - 3037.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Hudis
Trastuzumab -- Mechanism of Action and Use in Clinical Practice
N. Engl. J. Med.,
July 5, 2007;
357(1):
39 - 51.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. L. McArthur and S. Chia
Cardiotoxicity of Trastuzumab in Clinical Practice
N. Engl. J. Med.,
July 5, 2007;
357(1):
94 - 95.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Colozza, E. de Azambuja, N. Personeni, F. Lebrun, M. J. Piccart, and F. Cardoso
Achievements in Systemic Therapies in the Pregenomic Era in Metastatic Breast Cancer
Oncologist,
March 1, 2007;
12(3):
253 - 270.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Gabrielson, D. Bedja, S. Pin, A. Tsao, L. Gama, B. Yuan, and N. Muratore
Heat Shock Protein 90 and ErbB2 in the Cardiac Response to Doxorubicin Injury
Cancer Res.,
February 15, 2007;
67(4):
1436 - 1441.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. N. Harris, F. You, S. J. Schnitt, A. Witkiewicz, X. Lu, D. Sgroi, P. D. Ryan, S. E. Come, H. J. Burstein, B.-A. Lesnikoski, et al.
Predictors of Resistance to Preoperative Trastuzumab and Vinorelbine for HER2-Positive Early Breast Cancer
Clin. Cancer Res.,
February 15, 2007;
13(4):
1198 - 1207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. N. Munster, C. D. Britten, M. Mita, K. Gelmon, S. E. Minton, S. Moulder, D. J. Slamon, F. Guo, S. P. Letrent, L. Denis, et al.
First Study of the Safety, Tolerability, and Pharmacokinetics of CP-724,714 in Patients with Advanced Malignant Solid HER2-Expressing Tumors
Clin. Cancer Res.,
February 15, 2007;
13(4):
1238 - 1245.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Glazyrin, X. Shen, V. Blanc, and J. F. Eliason
Direct Detection of Herceptin/Trastuzumab Binding on Breast Tissue Sections
J. Histochem. Cytochem.,
January 1, 2007;
55(1):
25 - 33.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Moy and P. E. Goss
Lapatinib: Current Status and Future Directions in Breast Cancer
Oncologist,
November 1, 2006;
11(10):
1047 - 1057.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Guarneri, D. J. Lenihan, V. Valero, J.-B. Durand, K. Broglio, K. R. Hess, L. B. Michaud, A. M. Gonzalez-Angulo, G. N. Hortobagyi, and F. J. Esteva
Long-Term Cardiac Tolerability of Trastuzumab in Metastatic Breast Cancer: The M.D. Anderson Cancer Center Experience
J. Clin. Oncol.,
September 1, 2006;
24(25):
4107 - 4115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Gonzalez-Angulo, G. N. Hortobagyi, and F. J. Esteva
Adjuvant Therapy with Trastuzumab for HER-2/neu-Positive Breast Cancer
Oncologist,
September 1, 2006;
11(8):
857 - 867.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. L. Garland, M. Hidalgo, D. S. Mendelson, D. P. Ryan, B. K. Arun, J. L. Lovalvo, I. A. Eiseman, S. C. Olson, P. F. Lenehan, and J. P. Eder
A Phase I Clinical and Pharmacokinetic Study of Oral CI-1033 in Combination with Docetaxel in Patients with Advanced Solid Tumors.
Clin. Cancer Res.,
July 15, 2006;
12(14):
4274 - 4282.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Robert, B. Leyland-Jones, L. Asmar, R. Belt, D. Ilegbodu, D. Loesch, R. Raju, E. Valentine, R. Sayre, M. Cobleigh, et al.
Randomized Phase III Study of Trastuzumab, Paclitaxel, and Carboplatin Compared With Trastuzumab and Paclitaxel in Women With HER-2-Overexpressing Metastatic Breast Cancer
J. Clin. Oncol.,
June 20, 2006;
24(18):
2786 - 2792.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Chia, M. Clemons, L.-A. Martin, A. Rodgers, K. Gelmon, G. R. Pond, and L. Panasci
Pegylated Liposomal Doxorubicin and Trastuzumab in HER-2 Overexpressing Metastatic Breast Cancer: A Multicenter Phase II Trial
J. Clin. Oncol.,
June 20, 2006;
24(18):
2773 - 2778.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Piekarz, A. R. Frye, J. J. Wright, S. M. Steinberg, D. J. Liewehr, D. R. Rosing, V. Sachdev, T. Fojo, and S. E. Bates
Cardiac Studies in Patients Treated with Depsipeptide, FK228, in a Phase II Trial for T-Cell Lymphoma.
Clin. Cancer Res.,
June 15, 2006;
12(12):
3762 - 3773.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G. Horan, M. F. McMullin, and P. P. McKeown
Anthracycline cardiotoxicity
Eur. Heart J.,
May 2, 2006;
27(10):
1137 - 1138.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Papaldo, A. Fabi, G. Ferretti, M. Mottolese, A. M. Cianciulli, B. Di Cocco, M. S. Pino, P. Carlini, S. Di Cosimo, I. Sacchi, et al.
A phase II study on metastatic breast cancer patients treated with weekly vinorelbine with or without trastuzumab according to HER2 expression: changing the natural history of HER2-positive disease
Ann. Onc.,
April 1, 2006;
17(4):
630 - 636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. P. Coudert, L. Arnould, L. Moreau, P. Chollet, B. Weber, L. Vanlemmens, C. Molucon, N. Tubiana, S. Causeret, J.-L. Misset, et al.
Pre-operative systemic (neo-adjuvant) therapy with trastuzumab and docetaxel for HER2-overexpressing stage II or III breast cancer: results of a multicenter phase II trial
Ann. Onc.,
March 1, 2006;
17(3):
409 - 414.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Neyt, J. Albrecht, and V. Cocquyt
An economic evaluation of Herceptin(R) in adjuvant setting: the Breast Cancer International Research Group 006 trial
Ann. Onc.,
March 1, 2006;
17(3):
381 - 390.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Tan-Chiu, G. Yothers, E. Romond, C. E. Geyer Jr, M. Ewer, D. Keefe, R. P. Shannon, S. M. Swain, A. Brown, L. Fehrenbacher, et al.
Assessment of Cardiac Dysfunction in a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel, With or Without Trastuzumab As Adjuvant Therapy in Node-Positive, Human Epidermal Growth Factor Receptor 2-Overexpressing Breast Cancer: NSABP B-31
J. Clin. Oncol.,
November 1, 2005;
23(31):
7811 - 7819.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Ewer, M. T. Vooletich, J.-B. Durand, M. L. Woods, J. R. Davis, V. Valero, and D. J. Lenihan
Reversibility of Trastuzumab-Related Cardiotoxicity: New Insights Based on Clinical Course and Response to Medical Treatment
J. Clin. Oncol.,
November 1, 2005;
23(31):
7820 - 7826.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Floyd, D. T. Nguyen, R. L. Lobins, Q. Bashir, D. C. Doll, and M. C. Perry
Cardiotoxicity of Cancer Therapy
J. Clin. Oncol.,
October 20, 2005;
23(30):
7685 - 7696.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. H. Romond, E. A. Perez, J. Bryant, V. J. Suman, C. E. Geyer Jr., N. E. Davidson, E. Tan-Chiu, S. Martino, S. Paik, P. A. Kaufman, et al.
Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.
N. Engl. J. Med.,
October 20, 2005;
353(16):
1673 - 1684.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Campos, O. Hamid, M. V. Seiden, A. Oza, M. Plante, R. K. Potkul, P. F. Lenehan, E. P. Kaldjian, M. L. Varterasian, C. Jordan, et al.
Multicenter, Randomized Phase II Trial of Oral CI-1033 for Previously Treated Advanced Ovarian Cancer
J. Clin. Oncol.,
August 20, 2005;
23(24):
5597 - 5604.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. A. Burris III, H. I. Hurwitz, E. C. Dees, A. Dowlati, K. L. Blackwell, B. O'Neil, P. K. Marcom, M. J. Ellis, B. Overmoyer, S. F. Jones, et al.
Phase I Safety, Pharmacokinetics, and Clinical Activity Study of Lapatinib (GW572016), a Reversible Dual Inhibitor of Epidermal Growth Factor Receptor Tyrosine Kinases, in Heavily Pretreated Patients With Metastatic Carcinomas
J. Clin. Oncol.,
August 10, 2005;
23(23):
5305 - 5313.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Ewer and S. M. Lippman
Type II Chemotherapy-Related Cardiac Dysfunction: Time to Recognize a New Entity
J. Clin. Oncol.,
May 1, 2005;
23(13):
2900 - 2902.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. K. Mohsin, H. L. Weiss, M. C. Gutierrez, G. C. Chamness, R. Schiff, M. P. DiGiovanna, C.-X. Wang, S. G. Hilsenbeck, C. K. Osborne, D. C. Allred, et al.
Neoadjuvant Trastuzumab Induces Apoptosis in Primary Breast Cancers
J. Clin. Oncol.,
April 10, 2005;
23(11):
2460 - 2468.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. P Levene, G. Singh, and C. Palmieri
Therapeutic monoclonal antibodies in oncology
J R Soc Med,
April 1, 2005;
98(4):
146 - 152.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Baselga, X. Carbonell, N.-J. Castaneda-Soto, M. Clemens, M. Green, V. Harvey, S. Morales, C. Barton, and P. Ghahramani
Phase II Study of Efficacy, Safety, and Pharmacokinetics of Trastuzumab Monotherapy Administered on a 3-Weekly Schedule
J. Clin. Oncol.,
April 1, 2005;
23(10):
2162 - 2171.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Del Mastro, F. Perrone, L. Repetto, L. Manzione, V. Zagonel, L. Fratino, D. Marenco, M. Venturini, E. Maggi, C. Bighin, et al.
Weekly paclitaxel as first-line chemotherapy in elderly advanced breast cancer patients: a phase II study of the Gruppo Italiano di Oncologia Geriatrica (GIOGer)
Ann. Onc.,
February 1, 2005;
16(2):
253 - 258.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Bozionellou, D. Mavroudis, M. Perraki, S. Papadopoulos, S. Apostolaki, E. Stathopoulos, A. Stathopoulou, E. Lianidou, and V. Georgoulias
Trastuzumab Administration Can Effectively Target Chemotherapy-Resistant Cytokeratin-19 Messenger RNA-Positive Tumor Cells in the Peripheral Blood and Bone Marrow of Patients With Breast Cancer
Clin. Cancer Res.,
December 15, 2004;
10(24):
8185 - 8194.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Nieto, J. J. Vredenburgh, E. J. Shpall, S. I. Bearman, P. A. McSweeney, N. Chao, D. Rizzieri, C. Gasparetto, S. Matthes, A. E. Baron, et al.
Phase II Feasibility and Pharmacokinetic Study of Concurrent Administration of Trastuzumab and High-Dose Chemotherapy in Advanced HER2+ Breast Cancer
Clin. Cancer Res.,
November 1, 2004;
10(21):
7136 - 7143.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. A. Perez, V. J. Suman, N. E. Davidson, P. A. Kaufman, S. Martino, S. R. Dakhil, J. N. Ingle, R. J. Rodeheffer, B. J. Gersh, and A. S. Jaffe
Effect of Doxorubicin Plus Cyclophosphamide on Left Ventricular Ejection Fraction in Patients With Breast Cancer in the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial
J. Clin. Oncol.,
September 15, 2004;
22(18):
3700 - 3704.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. B. Riemer, M. Klinger, S. Wagner, A. Bernhaus, L. Mazzucchelli, H. Pehamberger, O. Scheiner, C. C. Zielinski, and E. Jensen-Jarolim
Generation of Peptide Mimics of the Epitope Recognized by Trastuzumab on the Oncogenic Protein Her-2/neu
J. Immunol.,
July 1, 2004;
173(1):
394 - 401.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. T.H. Yeh, A. T. Tong, D. J. Lenihan, S. W. Yusuf, J. Swafford, C. Champion, J.-B. Durand, H. Gibbs, A. A. Zafarmand, and M. S. Ewer
Cardiovascular Complications of Cancer Therapy: Diagnosis, Pathogenesis, and Management
Circulation,
June 29, 2004;
109(25):
3122 - 3131.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Minotti, P. Menna, E. Salvatorelli, G. Cairo, and L. Gianni
Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity
Pharmacol. Rev.,
June 1, 2004;
56(2):
185 - 229.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Karp, I. Gojo, R. Pili, C. D. Gocke, J. Greer, C. Guo, D. Qian, L. Morris, M. Tidwell, H. Chen, et al.
Targeting Vascular Endothelial Growth Factor for Relapsed and Refractory Adult Acute Myelogenous Leukemias: Therapy with Sequential 1-{beta}-D-Arabinofuranosylcytosine, Mitoxantrone, and Bevacizumab
Clin. Cancer Res.,
June 1, 2004;
10(11):
3577 - 3585.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Pegram, G. E. Konecny, C. O'Callaghan, M. Beryt, R. Pietras, and D. J. Slamon
Rational Combinations of Trastuzumab With Chemotherapeutic Drugs Used in the Treatment of Breast Cancer
J Natl Cancer Inst,
May 19, 2004;
96(10):
739 - 749.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Pegram, T. Pienkowski, D. W. Northfelt, W. Eiermann, R. Patel, P. Fumoleau, E. Quan, J. Crown, D. Toppmeyer, M. Smylie, et al.
Results of Two Open-Label, Multicenter Phase II Studies of Docetaxel, Platinum Salts, and Trastuzumab in HER2-Positive Advanced Breast Cancer
J Natl Cancer Inst,
May 19, 2004;
96(10):
759 - 769.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Burris III, D. Yardley, S. Jones, G. Houston, C. Broome, D. Thompson, F. A. Greco, M. White, and J. Hainsworth
Phase II Trial of Trastuzumab Followed by Weekly Paclitaxel/Carboplatin As First-Line Treatment for Patients With Metastatic Breast Cancer
J. Clin. Oncol.,
May 1, 2004;
22(9):
1621 - 1629.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. FOGLI, P. NIERI, and M. C. BRESCHI
The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage
FASEB J,
April 1, 2004;
18(6):
664 - 675.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Tripathy, D. J. Slamon, M. Cobleigh, A. Arnold, M. Saleh, J. E. Mortimer, M. Murphy, and S. J. Stewart
Safety of Treatment of Metastatic Breast Cancer With Trastuzumab Beyond Disease Progression
J. Clin. Oncol.,
March 15, 2004;
22(6):
1063 - 1070.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Lemmens, P. Fransen, S. U. Sys, D. L. Brutsaert, and G. W. De Keulenaer
Neuregulin-1 Induces a Negative Inotropic Effect in Cardiac Muscle: Role of Nitric Oxide Synthase
Circulation,
January 27, 2004;
109(3):
324 - 326.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. A. Perez and R. Rodeheffer
Clinical Cardiac Tolerability of Trastuzumab
J. Clin. Oncol.,
January 15, 2004;
22(2):
322 - 329.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Gatzemeier, G. Groth, C. Butts, N. Van Zandwijk, F. Shepherd, A. Ardizzoni, C. Barton, P. Ghahramani, and V. Hirsh
Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer
Ann. Onc.,
January 1, 2004;
15(1):
19 - 27.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Jones
Combining trastuzumab (Herceptin(R)) with hormonal therapy in breast cancer: what can be expected and why?
Ann. Onc.,
December 1, 2003;
14(12):
1697 - 1704.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Bianchi, J. Albanell, W. Eiermann, G. Vitali, D. Borquez, L. Vigano, R. Molina, G. Raab, A. Locatelli, B. Vanhauwere, et al.
Pilot Trial of Trastuzumab Starting with or after the Doxorubicin Component of a Doxorubicin plus Paclitaxel Regimen for Women with HER2-Positive Advanced Breast Cancer
Clin. Cancer Res.,
December 1, 2003;
9(16):
5944 - 5951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Cobleigh and D. Frame
Is Trastuzumab Every Three Weeks Ready for Prime Time?
J. Clin. Oncol.,
November 1, 2003;
21(21):
3900 - 3901.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Leyland-Jones, K. Gelmon, J.-P. Ayoub, A. Arnold, S. Verma, R. Dias, and P. Ghahramani
Pharmacokinetics, Safety, and Efficacy of Trastuzumab Administered Every Three Weeks in Combination With Paclitaxel
J. Clin. Oncol.,
November 1, 2003;
21(21):
3965 - 3971.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Nahta and F. J. Esteva
HER-2-Targeted Therapy: Lessons Learned and Future Directions
Clin. Cancer Res.,
November 1, 2003;
9(14):
5078 - 5084.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Rock and A. DeMichele
Nutritional Approaches to Late Toxicities of Adjuvant Chemotherapy in Breast Cancer Survivors
J. Nutr.,
November 1, 2003;
133(11):
3785S - 3793.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Burstein, L. N. Harris, P. K. Marcom, R. Lambert-Falls, K. Havlin, B. Overmoyer, R. J. Friedlander Jr., J. Gargiulo, R. Strenger, C. L. Vogel, et al.
Trastuzumab and Vinorelbine as First-Line Therapy for HER2-Overexpressing Metastatic Breast Cancer: Multicenter Phase II Trial With Clinical Outcomes, Analysis of Serum Tumor Markers as Predictive Factors, and Cardiac Surveillance Algorithm
J. Clin. Oncol.,
August 1, 2003;
21(15):
2889 - 2895.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kattlove and R. J. Winn
Ongoing Care of Patients After Primary Treatment for Their Cancer
CA Cancer J Clin,
May 1, 2003;
53(3):
172 - 196.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Geneve
Re: Demand Grows for Early Access to Promising Cancer Drugs
J Natl Cancer Inst,
March 19, 2003;
95(6):
492 - 492.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Burstein, L. N. Harris, R. Gelman, S. C. Lester, R. A. Nunes, C. M. Kaelin, L. M. Parker, L. W. Ellisen, I. Kuter, M. A. Gadd, et al.
Preoperative Therapy With Trastuzumab and Paclitaxel Followed by Sequential Adjuvant Doxorubicin/Cyclophosphamide for HER2 Overexpressing Stage II or III Breast Cancer: A Pilot Study
J. Clin. Oncol.,
January 1, 2003;
21(1):
46 - 53.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Page, D. Assouline, O. Brun, D. Coeffic, D. Fric, P. Winckel, A. D. Seidman, M. K. Pierri, and C. Hudis
Cardiac Dysfunction in Clinical Trials of Trastuzumab
J. Clin. Oncol.,
October 1, 2002;
20(19):
4119 - 4120.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Baselga
Why the Epidermal Growth Factor Receptor? The Rationale for Cancer Therapy
Oncologist,
August 15, 2002;
7(90004):
2 - 8.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Speyer
Cardiac Dysfunction in the Trastuzumab Clinical Experience
J. Clin. Oncol.,
March 1, 2002;
20(5):
1156 - 1157.
[Full Text]
[PDF]
|
|
|
|
TOP
ABSTRACT
INTRODUCTION
