25 april 2013: In BMC - British Journal of Cancer verscheen vorig jaar een publicatie van een fase 2 studie waarbij gesteld werd dat verder onderzoek naar herceptin bij alvleesklierkanker niet zinnig wordt veronderstelt. Ook omdat halverwege de studie nog weinig patiënten in leven waren en een minderheid van de patiënten de juiste mutatie hadden, slechts 11% (van ruim 200 deelnemende patienten) toonde een vorm van expressie geschikt voor herceptin. 

Maar wat hier naar mijn bescheiden mening aan de hand is dat deze studie werd uitgevoerd met mensen die uitbehandeld waren en in slechte lichamelijke conditie met al overal uitzaaiingen. Dan heeft een vorm van immuuntherapie, zoals herceptin toch in feite is, weinig zin meer. Gelukkig wordt er nog wel onderzoek gedaan naar aanpak van alvleesklierkanker op basis van zogeheten dual aanpak, een aanpak op basis van een vastgestelde EGFR en Her2Neu expressie vooraf, zie o.a. dit studierapport: In Pancreatic Carcinoma, Dual EGFR/HER2 Targeting with Cetuximab/Trastuzumab Is More Effective than Treatment with Trastuzumab/Erlotinib or Lapatinib Alone: Implication of Receptors' Down-regulation and Dimers' Disruption1

 Het volledige studierapport in BMC waarbij herceptin geen goede aanpak zou zijn kunt u gratis inzien. Het abstract staat onderaan dit artikel.

8 mei 2012: als aanvulling op onderstaande dierstudies van herceptin - trastuzumab bij alvleesklierkanker  het abstract van een fase I studie bij 12 alvleesklierkankerpatiënten toegevoegd met hoopvolle resultaten.

Als u hier klikt kunt u gratis een studierapport inzien waar geanalyseerd is wat een te hoge Her2-Neu expressie betekent voor mensen met spijsverteringskanker zoals alvleesklierkanker. Her2-neu expressie is bepalend of een kankerpatiënt in aanmerking komt voor herceptin of niet.

Onderaan staat het abstract van de studie plus referentielijst.

17 september 2005: Bron: Int J Oncol. 2005 Oct;27(4):1125-30.

Duitse onderzoekers publiceren in oktober a.s. het abstract van een aantal laboratoriumstudies en dierstudies die ze gedaan hebben met Herceptin als basis aangevuld met gemcitabine en/of docetaxel bij inoperabele en gevorderde alvleesklierkanker. Omdat bij 70% van de alvleesklierkankerpatiënten de HER2-Neu expressie oververtegenwoordigd is en juist Herceptin bij borstkankerpatiënten met deze receptor uitstekende resultaten laat zien zijn deze trials opgezet. Nu worden fase I en II studies opgezet bij alvleesklierkankerpatiënten om te zien of de goede resultaten uit de laboratoriumproeven en dierstudies dan ook overeind blijven.

Combination therapy for advanced pancreatic cancer using Herceptintrade mark plus chemotherapy.

Buchler P, Reber HA, Eibl G, Roth MA, Buchler MW, Friess H, Isacoff WH, Hines OJ.
Department of General Surgery, Ruprecht-Karls-University of Heidelberg, D-69120 Heidelberg, Germany. peter.buechler@med.uni-heidelberg.de.

The HER2/neu oncogene is overexpressed in up to 70% of human pancreatic cancer specimens when compared to normal pancreatic tissue. This cell surface receptor can be targeted specifically by the neutralizing antibody Herceptintrade mark. Herceptin has been successfully used in combination with other chemotherapeutic agents in breast cancer, a cancer in which only 30% of patients harbor elevated HER2/neu levels. In the present study, we investigated the therapeutic efficacy of Herceptin in combination with gemcitabine and docetaxel. Gemcitabine is currently the standard chemotherapeutic agent used to treat pancreatic cancer. In contrast, docetaxel, a taxane, is only just being investigated in pancreatic cancer. Tumor cell resistance to taxanes is at least in part mediated by the HER2/NEU oncogene. We have previously characterized HER2/NEU expression in human pancreatic cancer cell lines and studied the anti-tumor activity of Herceptin monotherapy in vitro and in vivo. In the present study, combination therapy resulted in a dramatic improvement of animals bearing human pancreatic cancer xenografts. Furthermore, metastasis and production of ascites was lower when a combination of these three agents was used. We conclude that, as with breast cancer, the anti-tumor activity of Herceptin may be improved by combination with taxanes or gemcitabine.

PMID: 16142331 [PubMed - in process]

HER2 as a Prognostic Marker in Gastric Cancer - A Systematic Analysis of Data from the Literature

 J Cancer. 2012; 3 : 137–144.
Published online 2012 March 12. doi:  10.7150/jca.4090
PMCID: PMC3319979
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
HER2 as a Prognostic Marker in Gastric Cancer - A Systematic Analysis of Data from the Literature
Jan Trøst Jørgensen1 and Maria Hersom2
1. Dx-Rx Institute, Baunevaenget 76, DK-3480 Fredensborg, Denmark;
2. Human Biology, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Corresponding author: Dx-Rx Institute, Baunevaenget 76, DK-3480 Fredensborg, Denmark, Phone: +45 4074 7846, Fax: +45 8870 8090, E-mail: jan.trost@dx-rx.dk .
Competing Interests: Jan Trøst Jørgensen has worked as a consultant for Dako Denmark A/S, Glostrup, Denmark and has given lectures at meetings sponsored by Roche and AstraZeneca. Maria Hersom has nothing to disclose.
Received January 14, 2012; Accepted March 4, 2012.
Abstract
Through the recent conduct of the ToGA trial, HER2 has shown to be predictive for the treatment with trastuzumab in advanced gastric and gastro-oesophageal cancer. When it comes to the prognostic properties the situation is different. Despite the fact that it is more than 20 years ago since the first studies demonstrating an association between a positive HER2 status and poor prognosis were published the issue is still controversial. In this current systematic review a large number of studies on HER2 and gastric cancer have been reviewed. The studies included in this review should fulfill the following two criteria. First criterion: The number of patients in each study should be ≥ 100, and the HER2 status should have been determined either by immunohistochemistry (IHC) or in situ hybridization (ISH). Second criterion: The selected articles should include an analysis of the association between the HER2 status and survival or relevant clinicopathological characteristics. Forty-two publications with a total of 12,749 patients fulfilled the two criteria and were reviewed in detail. The majority of the publications (71%) showed that a HER2-postive status measured either by IHC or ISH was associated with poor survival and/or clinicopathological characteristics, such as serosal invasion, lymph node metastases, disease stage, or distant metastases. Based on the current analysis a clear trend towards a potential role for HER2 as a negative prognostics factor in gastric cancer was shown, suggesting that HER2 overexpression and/or amplification is a molecular abnormality that might be linked to the development of gastric cancer.
Keywords: HER2, gastric cancer, prognostic marker, IHC, FISH, CISH.
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Multicentre phase II trial of trastuzumab and capecitabine in patients with HER2 overexpressing metastatic pancreatic cancer

British Journal of Cancer (2012) 106, 1033–1038. doi:10.1038/bjc.2012.18 www.bjcancer.com
Published online 28 February 2012

Multicentre phase II trial of trastuzumab and capecitabine in patients with HER2 overexpressing metastatic pancreatic cancer

J Harder1, G Ihorst2, V Heinemann3, R Hofheinz4, M Moehler5, P Buechler6, G Kloeppel7, C Röcken7, M Bitzer8, S Boeck3, E Endlicher9, A Reinacher-Schick10, C Schmoor2 and M Geissler11

  1. 1Medizinische Klinik II, Hegau- Bodensee Klinikum, Virchowstraße 10, D-78224 Singen, Germany
  2. 2Clinical Trials Unit, University Medical Center Freiburg, Elsässer Straße 2, D-79110 Freiburg, Germany
  3. 3Klinikum Grosshadern Medizinische Klinik III, L.M.- Universitätsklinikum München, Marchoninistraße 15, D-81377 München, Germany
  4. 4Medizinische Klinik III, Klinikum Mannheim, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
  5. 5Medizinische Klinik und Poliklinik, Klinikum der Johannes Gutenberg- Universität Mainz, Langenbeckstraße 1, D-55131 Mainz, Germany
  6. 6Abt. Allgemeine,- Viszerale-u. Unfallchirurgie, Chirurgische Universitätsklinik Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany
  7. 7Institut f. Pathologie, Christian-Albrechts-Universität, Arnold Heller-Straße 3, D-24105 Kiel, Germany
  8. 8Medizinische Klinik I, Universitätsklinikum Tübingen, Ottfried-Müller- Straße 10, D-72076 Tübingen, Germany
  9. 9Klinik und Poliklinik für Innere Medizin I, Klinikum der Universität Regensburg, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg, Germany
  10. 10Hämatologie/Onkologie, Knappschaftskrankenhaus Bochum, In der Schornau 23–25, D-44892 Bochum, Germany
  11. 11Klinik für Allg. Innere Medizin, Onkologie/Hämatologie, Gastroenterologie u. Infektiologie, Klinikum Esslingen, Hirschlandstraße. 97, D-73730 Esslingen, Germany

Correspondence: Dr J Harder, E-mail: jan.harder@hbh-kliniken.de

Received 7 July 2011; Revised 6 January 2012; Accepted 12 January 2012
Advance online publication 28 February 2012

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Abstract

Background:

  

New therapeutic options for metastatic pancreatic cancer are urgently needed. In pancreatic cancer, overexpression of the epidermal growth factor receptor 2 (HER2) has been reported in up to 45%. This multicentre phase II study investigated the efficacy and toxicity of the HER2 antibody trastuzumab combined with capecitabine in the patients with pancreatic cancer and HER2 overexpression.

Methods: 

Primary endpoint was progression-free survival (PFS) after 12 weeks. A total of 212 patients were screened for HER2 expression.

Results:

Immunohistochemical (IHC) HER2 expression was: 83 (40%) grade 0, 71 (34%) grade 1, 31 (15%) grade 2, 22 (11%) grade 3. A total of 17 patients with IHC +3 HER2 expression or gene amplification could be assessed for the treatment response. Grade 3/4 treatment toxicities were: each 7% leucopenia, diarrhoea, nausea and hand-foot syndrome. Progression-free survival after 12 weeks was 23.5%, median overall survival (OS) 6.9 months.

Conclusion: 

This study demonstrates +3 HER2 expression or gene amplification in 11% of patients. Contrary to breast and gastric cancer, only 7 out of 11 (64%) patients with IHC +3 HER2 expression showed gene amplification. Although the therapy was well tolerated, PFS and OS did not perform favourably compared with standard chemotherapy. Together, we do not recommend further evaluation of anti-HER2 treatment in patients with metastatic pancreatic cancer.

alvleesklierkanker, EGFR, Her2-Neu, trastuzumab, herceptin


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