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Klinische Relevanz der Modulation von zytostatika durch Zytokine beim metastasierten kolorektalen Karzinom

Clinical relevance of the modulation of cytotoxic drugs by cytokines in metastatic colorectal carcinoma

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Zusammenfassung

Sowohl in der adjuvanten als auch der palliativen Chemotherapie des kolorektalen Karzinoms werden derzeit biochemische und immunologische Modulatoren auf ihre Wirkungsverstärkung von 5-Fluorouracil (5-FU) in Phase-II- und-III-Studien überprüft.

In der adjuvanten therapie des Kolonkarzinoms im Stadium Dukes C ist für 5-FU und Levamisol ein signifikanter Überlebensvorteil nachgewiesen worden. Eine postoperative lokale Nachbestrahlung und 5-FU-haltige Chemotherapie kann beim Rektumkarzinom die lokale Rezidivrate signifikant senken und das Überleben verlängern. Liegen Fernmetastasen vor, wird durch eine biochemische Modulation mit 5-FU und Folinsäure eine Remissionsrate gegenüber 5-FU alleine signifikant verbessert (30% vs. 12%). Deshalb gilt diese Kombination als Therapie der 1. Wahl, wobei noch nicht gesichert ist, ob die Erhöhung der Remissionsrate zu einem überlebensvorteil und einer Erhöhung der Lebensqualität führt. Durch eine intermediäre Infusion von 5-FU (2 bis 4 Studen) können die Nebenwirkungen im Vergleich zur Bolusapplikation verringert werden. PALA, Dipyridamol, Cisplatin und Methotrexat sind biochemische Modulatoren, welche die Wirksamkeit von 5-FU nicht signifikant verbessern können. Die Rolle der Immuntherapie beim kolorektalen Karzinom ist noch nicht definiert. Interferon alpha, beta, gamma sowie Tumornekrosefaktor alpha und deren Kombinationen sind beim fortgeschrittenen kolorektalen Karzinom unwirksam. Durch Interferon und 5-FU wurden im Median 25% Remissionen beschrieben.

Der endgültige Stellenwert dieser biochemischen und immunologischen Modulatoren in der adjuvanten und palliativen Chemotherapie des kolorektalen Karzinoms muß noch in Phase-III-Studien definiert werden.

Summary

Various biochemical and immunologic modulators are presently tested in phase II/III trials to determine their synergistic effects on 5-fluorouracil (5-FU) in adjuvant and in palliative chemotherapy of colorectal carcinoma.

5-FU and levamisole in adjuvant therapy of Dukes C colon carcinoma show a significant survival advantage. In rectal cancer, the combination of postoperative local radiation and 5-FU-based systemic therapy can significantly reduce the local relapse rate and improve survival. In advanced colorectal carcinoma, the biochemical modulation with 5-FU and folinic acid can significantly improve the response rates compared to 5-FU alone (30% vs. 12%). Therefore, this combination is considered as the standard treatment, although so far this advantage could not be translated into improved survival and quality of life. Compared to bolus application an intermediate infusion of 5-FU (2 to 4 hours) can largely reduce side effects. PALA, dipyridamole, cisplatin, and methotrexate are biochemical modulators that cannot improve the efficacy of 5-FU significantly. Interferon alpha, beta, gamma, tumor necrosis factor alpha, and their combinations are ineffective in advanced colorectal cancer. Median response rates of 25% have been reported after application of interferon and 5-FU.

The final value of the various biochemical and immunological modulators in adjuvant and palliative chemotherapy of colorectal carcinoma remains to be defined in phase III trials.

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  1. Abteilung für Innere Medizin mit Schwerpunkt Hämatologie und Onkologie Klinikums Steglitz der Freien Universität Berlin, Hindenburghdamm 30, D-1000, Berlin 45, Deutschland

    R. U. Hilgenfeld, E. -D. Kreuser & E. Thiel

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Hilgenfeld, R.U., Kreuser, E.D. & Thiel, E. Klinische Relevanz der Modulation von zytostatika durch Zytokine beim metastasierten kolorektalen Karzinom. Acta Chir Austriaca 23, 218–228 (1991). https://doi.org/10.1007/BF02663229

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