Vitamins and Micronutrients as Preventive Agents for Prostate Cancer - Evidence and Proposal for Rapid Throughput Evaluation

Zusammenfassung

Möglichkeiten des Einsatzes des Prostata-spezifischen Antigens (PSA) als Ersatz-Marker im klinischen Bereich sowie die Verwendung des PSA bei der Untersuchung von Tumorgewebe von orthotopisch mit menschlichem Prostatakarzinomgewebe transplantierten Nacktmäusen werden diskutiert. Die Erfassung des PSA-Wert-Anstiegs bzw. deren Verdoppelungszeit erlaubt bedeutend kürzere Versuchsmengen und -zeiten. Eine positive, auf PSA-Werten beruhende klinische Studie, die durch Experimente mit Nacktmäusen bestätigt wird, kann es erlauben, direkt mit einer Untersuchung eines neuen Arzneimittels der Klasse III oder einer Präventivdiät zu beginnen. Auf der anderen Seite spart man im Fall eines negativen Ergebnisses viel Geld und Zeit. Positive Ergebnisse von Untersuchungen mit der neuen Methode für die Wirkung von Nahrungsmittelzusätzen bei Männern mit ansteigenden PSA-Werten nach potenziell heilenden Eingriffen und Ergebnisse einer Studie mit Lycopen und Vitamin E bei orthotopischen Transplantationen der PC-346C Zelllinie von Nacktmäusen werden vorgestellt. Zur Zeit laufen mehrere Untersuchungen mit neuen Medikamenten und Mikronährstoffen.

Summary

In this contribution, a summary is given of efforts to establish PSA as a surrogate marker in tertiary prevention studies based on PSA in the clinical setting and utilizing PSA in relation to tumor mass studied in nude mice bearing human prostate cancer tissue in orthotopic transplants. The use of PSA slope or doubling time results in remarkably small sample sizes and short duration of trials. A positive PSA-based clinical study confirmed by an experimental study in nude mice may justify to move directly to a phase III exploration of a new drug or preventive regimen. On the other hand, much cost and effort can be saved if the PSA-based clinical study and the animal confirmation study were negative. Results of positive exploratory studies employing this new methodology, relating to a dietary supplement and its application to men with rising PSA after potentially curative management, and results of a study with lycopene and vitamine E in orthotopic transplants of the PC-346C cell line in nude mice are presented. Several studies with new drugs and micronutrients using this new approach are currently on-going.

Schlüsselwörter

Prostatakarzinom - natürlicher Verlauf - Epidemiologie - Prävention - Untersuchungsmethoden - Endpunkt

Key words

Prostate cancer - natural history - epidemiology - prevention - trial methodology - end-points

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