Rationale for heparin treatment of colon cancer

Summary

It is widely known that the systemic blood coagulation mechanism is often activated in malignancy, leading to an increased incidence of vascular thromboses in patients with cancer. It is not widely appreciated, however, that products of the coagulation mechanism may also support tumor growth and dissemination. Interest in this approach to cancer therapy has surged recently because of mounting evidence that the familiar anticoagulant drug, heparin, may impede tumor progression. Heparin has the capacity to modify angiogenesis, growth factor and protease activity, immune function, cell proliferation and gene expression in ways that may block malignant dissemination. Clinical trials in which heparin has been administered to a broad spectrum of patients to prevent or treat thrombosis have unexpectedly shown improvement in survival in the subset of patients with malignancy entered to these studies. Meta-analyses of clinical trials comparing unfractionated (UF) versus low molecular weight (LMW) heparin treating venous thromboembolism suggest that there may be substantial improvement in cancer outcome in patients with malignancy randomized to receive LMW heparin. These findings provide a rationale for definitive clinical trials of LMW heparin in cancer, and the results of several such studies that are currently underway are awaited with interest.

Zusammenfassung

Man weiß, dass maligne Erkrankungen häufig mit einer Aktivierung der systemischen Blutgerinnung einhergehen, was bei Krebspatienten zu einer erhöhten Inzidenz von Gefäßthromben führt. Wenig bekannt ist dagegen, dass Produkte der Blutgerinnung auch das Wachstum und die Dissemination von Tumoren fördern können. Diese Tatsache wurde wiederholt in Tiermodellen deutlich, in denen Antikoagulanzien das Tumorwachstum und die Metastasierung verzögerten. Die Beobachtungen am Modell gaben Anlass zu Studien mit oralen Antikoagulanzien beim Menschen, die bei bestimmten Tumorarten vielversprechende frühe Resultate lieferten. Das Interesse an diesem Ansatz der Krebstherapie hat in neuerer Zeit aufgrund der sich mehrenden Hinweise, dass das bekannte Antikoagulans Heparin eine Tumorprogression verhindern könnte, zugenommen. Heparin vermag Angiogenese, Wachstumsfaktor- und Proteaseaktivitäten, Immunfunktion, Zellproliferation und Genexpression derart zu modifizieren, dass die Dissemination des Malignoms blockiert werden könnte. Klinische Studien, in denen Heparin an ein breites Patientenspektrum als Thromboseprophylaxe oder -therapie verabreicht wurde, haben unerwartet eine Verbesserung der Faktors »Überleben« bei denjenigen Patienten der Studien gezeigt, die an einer malignen Erkrankung litten. Eine Meta-Analyse klinischer Studien, die unfraktioniertes (UF) und niedermolekulares Heparin (NMH) bei der Behandlung von venösen Thromboembolien verglichen, deutet an, dass es bei Krebs-Patienten, die NMH erhielten, zu einem wesentlich günstigeren Verlauf der malignen Erkrankung kommen könnte. Diese Befunde bieten die Grundlage für definitive klinische Studien zu NMH an Krebs-Patienten. Die Ergebnisse mehrerer solcher derzeit laufender Studie werden mit Interesse erwartet.

Keywords

Cancer - anticoagulant treatment - heparin

Schlüsselwörter

Krebs - antikoagulatorische Therapie - Heparin

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