Herceptin - trastuzumab geeft significant minder kans op recidief naast verschillende chemokuren bij borstkanker stadium I, II en III.

14 november 2008: Bron: Pubmed en ASCO: Nieuwe fase III studies bewijzen dat Herceptin naast verschillende soorten chemo zorgt voor significant minder recidieven bij borstkanker (33% tot 40%) en signficant langere ziektevrije tijd in vergelijking met alleen chemo. Voor OPS donateurs hebben we een 6 pagina's groot studieverslag over herceptin bij de twee verschillende chemokuren. Inclusief de gevaren en bijwerkingen enz. Wel is het Engelstalig maar is een zeer gedetailleerd rapport en handig om mee te nemen naar uw oncoloog. Zie verderop in deze artikelen ook dat uw Her2-Neu expressie kan veranderen door hormoongebruik of sowieso in de loop van de tijd. U zou dus best nu wel in aanmerking kunnen komen voor herceptin. Hieronder de resultaten van de laatste fase III studies en het schema zoals herceptin wordt gegeven naast de chemo. Daaronder nog enkele studies al uit 2003 over herceptin.

Results

In this study, both the TCH and AC→TH arms demonstrated improved DFS compared with the chemotherapy-alone control arm (AC→T). Compared with AC→T, TCH reduced the relative risk of recurrence by 33% (hazard ratio of 0.67, confidence interval 0.54-0.84; P=0.0006), and AC→TH reduced the relative risk of recurrence by 40% (HR of 0.60, CI: 0.48-0.76; P≤0.0001). The DFS benefit of TCH and AC→TH was seen across multiple patient subsets, including age ≤39 years, hormone receptor negative, 4 to 9 positive nodes, and tumor size >2 cm.

The non-anthracycline-containing TCH regimen was associated with a reduction in the incidence of congestive heart failure (CHF) as compared with the AC→TH arm. CHF occurred in 0.4% of patients in the TCH arm vs 2% of patients in the AC→TH arm and 0.3% of patients in the AC→T arm. Grade 3/4 cardiac ischemia or infarction occurred in 0.3% of patients randomized to the AC→TH arm and in 0.2% of those in the TCH arm, compared with 0% in the AC→T arm. With the exception of the lower incidence of CHF in the TCH arm, adverse event profiles were similar to those observed in previous trials of Herceptin plus chemotherapy in the adjuvant setting.

Mei 2003: Bron: o.a. Roche Nederland

Wel of geen chemo bij borstkanker. Een eeuwig durend dilemma lijkt het wel. Wat in Nederland nog niet erg gebruikelijk is, maar nu al wel in Duitsland en Amerika vaker wordt gegeven; Herceptin oftewel trastuzumab een zogeheten monoklonaal middel geeft al of niet in combinatie met bepaalde chemo's een significant beter resultaat dan standaard chemo zonder herceptin, bij niet hormoongevoelige borstkanker met overwegend HER2 Neu expressie in het voorkomen van een recidief of het verlengen van het leven. De FDA (Federal Drugs Administration) gaf recent toestemming voor eerste lijnsbehandeling bij gemetasteerde borstkanker docecatel met paclitaxel en aanvullend trastuzumab. Hieronder de abstracten van enkele belangwekkende studies die bewijzen dat herceptin/trastuzumab significant betere resultaten geeft in gemiddelde overlevingstijd, meer complete responsgevallen en minder ernstige bijwerkingen dan standaard chemo zoals bv. doxorubicin of docetaxel of epirubicin of cyclophosphamide, hoewel ook herceptin wel bijwerkingen geeft. Wie een volledige studiebeschrijving van Herceptin naast twee verschillende chemococktails wil kan ik die digitaal op verzoek toesturen. Maar handig misschien om eens met uw oncoloog van gedachten te wisselen aan de hand van onderstaande informatie over een behandeling met herceptin, al of niet in combinatie met een standaard chemo of zelfs als stand alone behandeling. Overigens geeft Xeloda ook goede resultaten in fase II en III studies bij gemetasteerde borstkanker. M.i. is het altijd handig om welke behandeling dan ook te ondersteunen met gezond eten - bv. Houtsmullerdieet - en aanvullende vitamines enz. Raadpleeg daarvoor een orthomoleculaire arts. Weerstand en immuunversterkende middelen zijn altijd goed lijkt me, ook bij borstkanker, maar vooral naast chemo.

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
By Melody A. Cobleigh, Charles L. Vogel, Debu Tripathy, Nicholas J. Robert, Susy Scholl, Louis Fehrenbacher, Janet M. Wolter, Virginia Paton, Steven Shak, Gracie Lieberman, and Dennis J. Slamon

Purpose: Overexpression of the HER2 protein occurs in 25% to 30% of human breast cancers and leads to a particularly aggressive form of the disease. Efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody as a single agent was evaluated in women with HER2-overexpressing metastatic breast cancer that had progressed after chemotherapy for metastatic disease.

Patients and Methods: Two hundred twenty-two women, with HER2-overexpressing metastatic breast cancer that had progressed after one or two chemotherapy regimens, were enrolled. Patients received a loading dose of 4 mg/kg intravenously, followed by a 2-mg/kg maintenance dose at weekly intervals.

Results: Study patients had advanced metastatic disease and had received extensive prior therapy. A blinded, independent response evaluation committee identified eight complete and 26 partial responses, for an objective response rate of 15% in the intent-to-treat
population (95% confidence interval, 11% to 21%). The median duration of response was 9.1 months; the median duration of survival was 13 months. The most common adverse events, which occurred in approximately 40% of patients, were infusion-associated fever and/or chills that usually occurred only during the first infusion, and were of mild to moderate severity. These symptoms were treated successfully with acetaminophen and/or diphenhydramine. The most clinically significant adverse event was cardiac dysfunction, which occurred in 4.7% of patients. Only 1% of patients discontinued the study because of treatment-related adverse events.

Conclusion: Recombinant humanized anti-HER2 mono-clonal antibody, administered as a single agent, produces urable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for
metastatic disease. Side effects that are commonly observed with chemotherapy, such as alopecia, mucositis, and neutropenia, are rarely seen.
J Clin Oncol 17:2639-2648.r 1999 by American Society of Clinical Oncology.

The New England Journal of Medicine Copyright ©2001 by the Massachusetts Medical Society
VOLUME 344 MARCH 15,2001 NUMBER 11 N Engl J Med,Vol.344,No.11 ·March 15,2001 ·www.nejm.org ·783

USE OF CHEMOTHERAPY PLUS A MONOCLONAL ANTIBODY GAINST HER2 FOR METASTATIC BREAST CANCER THAT OVEREXPRESSES HER2 DENNIS J.SLAMON,M.D.,PH.D.,BRIAN LEYLAND-JONES,M.D.,STEVEN SHAK,M.D.,HANK FUCHS,M.D., VIRGINIA PATON,PHARM.D.,ALEX BAJAMONDE,PH.D.,THOMAS FLEMING,PH.D.,WOLFGANG EIERMANN,M.D., JANET WOLTER,M.D.,MARK PEGRAM,M.D.,JOSE BASELGA,M.D.,AND LARRY NORTON,M.D.*
ABSTRACT
Background The HER2 gene,which encodes the growth factor receptor HER2,is amplified and HER2 is overexpressed in 25 to 30 percent of breast cancers increasing the aggressiveness of the tumor.

Methods:
We evaluated the efficacy and safety of trastuzumab,a recombinant monoclonal antibody against HER2,in women with metastatic breast cancer that overexpressed HER2.We randomly assigned 234 patients to receive standard chemotherapy alone and 235 patients to receive standard chemotherapy plus trastuzumab. Patients who had not previously received adjuvant (postoperative)therapy with an anthracycline were treated with doxorubicin (or epirubicin in the case of 36 women)and cyclophosphamide with (143 women)or without trastuzumab (138 women).Patients who had previously received adjuvant anthracycline were treated with paclitaxel alone (96 women)or paclitaxel with trastuzumab (92 women).

Results:
The addition of trastuzumab to chemotherapy was associated with a longer time to disease pgression (median,7.4 vs.4.6 months;P<0.001),a higher rate of objective response (50 percent vs.32 percent, P<0.001),a longer duration of response (median,9.1 vs.6.1 months;P<0.001),a lower rate of death at 1 year (22 percent vs.33 percent,P=0.008),longer survival (median survival,25.1 vs.20.3 months;P=0.046),and a 20 percent reduction in the risk of death.The most important adverse event was cardiac dysfunction, which occurred in 27 percent of the group given an anthracycline,cyclophosphamide,and trastuzumab; 8 percent of the group given an anthracycline and cyclophosphamide alone;13 percent of the group given paclitaxel and trastuzumab;and 1 percent of the group given paclitaxel alone.Although the cardiotoxicity was potentially severe and,in some cases life-threatening,the symptoms generally improved with standard medical management.
Conclusions Trastuzumab increases the clinical benefit of first-line chemotherapy in metastatic breast cancer that overexpresses HER2.(N Engl J Med 2001; 344:783-92.)
Copyright ©2001 Massachusetts Medical Society. From the Division of Hematology and Oncology,UCLA School of Medicine,Los Angeles (D.J.S.,M.P.);the Department of Oncology,
McGill University,Montreal (B.L.-J.):Medical Affairs,Genentech,South San Francisco,Calif.(S.S.,V.P.,A.B.);IntraBiotics,Mountain View,Calif. (H.F.);the Department of Biostatistics,University of Washington,Seattle (T.F.);the Department of Obstetrics and Gynecology,Frauenklinik vom Roten Kreuz,Munich,Germany (W.E.);the Department of Oncology,
Rush –Presbyterian –St.Luke ’s Medical Center,Chicago (.W.);the Depart-
ment of Oncology,Hospital General Universitari Vall d ’Hebron,Barcelo-
na,Spain (J.B.);and the Department of Medical Oncology,Memorial
Sloan-Kettering Cancer Center,New York (L.N.).Address reprint requests
to Dr.Slamon at UCLA School of Medicine,Division of Hematology/
Oncology,11-244 Factor Bldg.,10833 Le Conte,Los Angeles,CA 90095-
1678,or at dslamon@mednet.ucla.edu.

Phase II Study of Weekly Docetaxel and Trastuzumab for Patients With HER-2–Overexpressing Metastatic Breast Cancer
By Francisco J. Esteva, Vicente Valero, Daniel Booser, Laura T. Guerra, James L. Murray, Lajos Pusztai, Massimo Cristofanilli, Banu Arun, Bita Esmaeli, Herbert A. Fritsche, Nour Sneige, Terry L. Smith, and Gabriel N. Hortobagyi

Purpose: To evaluate the safety and efficacy of weekly docetaxel plus trastuzumab in women with HER-2–overexpressing metastatic breast cancer. Efficacy was correlated with serum HER-2 extracellular domain (ECD) levels.
Patients and Methods: Thirty women with metastatic breast cancer were treated with weekly docetaxel and trastuzumab as first- or second-line therapy. Both docetaxel 35 mg/m 2 /wk and trastuzumab 2 mg/kg/wk were delivered in 4-week cycles consisting of three weekly treatments followed by 1 week of rest. A loading dose of trastuzumab 4 mg/kg was administered
1 day before the start of the first cycle.
Results: The median delivered dose-intensity of docetaxel was 24 mg/m 2 /wk (range, 18 to 27 mg/m 2 /wk). The intent-to-treat overall response rate (ORR) was 63% (95% confidence interval , 44% to 80%). The ORR in patients whose tumors were HER-2–positive by fluorescence in situ hybridization was 67% (16 of 24 patients; 95% CI, 45% to 84%). In patients with elevated serum HER-2 ECD at baseline, the ORR was 76% (95% CI, 53% to 92%), compared with 33% (95% CI, 7% to 70%) in patients with low HER-2 ECD levels (P .04).
Variations in HER-2 ECD concentrations during treatment correlated with response to treatment. Median time to progression was 9 months. Acute toxicity, including myelosuppression, was mild. Fatigue, fluid retention, and excessive tearing became more common with repetitive dosing.
Conclusion: Weekly docetaxel and trastuzumab is an active combination for treating patients with HER-2– overexpressing metastatic breast cancer. Serum HER-2 ECD testing may be a promising method for monitoring patients on trastuzumab-based therapy.
J Clin Oncol 20:1800-1808. © 2002 by American Society of Clinical Oncology.

Trastuzumab/Chemotherapy Combinations in Metastatic Breast Cancer
Jennifer A. Ligibel and Eric P. Winer

The past decade has seen many advances in the treatment of advanced breast cancer, including the development of both new chemotherapy drugs and novel targeted agents. Trastuzumab, a humanized monoclonal antibody directed against the HER2/neu protein, has been shown to be an efficacious treatment for HER2-overexpressing metastatic breast cancer, both as a single agent and when used in combination with chemotherapy. The US Food and Drug Administration has approved the use of trastuzumab and paclitaxel as first-line treatment of HER2-overexpressing metastatic breast cancer, based on the results of a randomized phase III clinical trial showing that this combination produced higher response rates and longer survival duration than treatment with chemotherapy alone. Further trials are currently underway evaluating the use of trastuzumab in combination with other forms of chemotherapy, including vinorelbine, docetaxel, anthracyclines, and platinum agents. Hopefully, information from these trials will help resolve questions regarding the efficacy of various combinations and dosing schedules so that trastuzumab may be used most effectively in the treatment of HER2-over-expressing breast cancer in both the metastatic and the adjuvant settings.
Semin Oncol 29 (suppl 11):38-43. Copyright 2002, Elsevier Science (USA). All rights reserved.