Stellenwert von Oxaliplatin in der Therapie des fortgeschrittenen kolorektalen Karzinoms

Zusammenfassung

In präklinischen Modellen und in zahlreichen Phase-I- bis -III-Untersuchungen wurde die Wirksamkeit des Zytostatikums Oxaliplatin (L-OHP) beim kolorektalen Karzinom nachgewiesen. Bei nicht vorbehandelten Patienten sind die Ansprechraten mit L-OHP plus 5-Fluorouracil und Leukovorin (5-FU/LV) mehr als doppelt so hoch wie mit 5-FU/LV allein und das progressionsfreie Intervall wird signifikant verlängert. Trotzdem ist die Gesamtüberlebenszeit in den Therapiearmen ähnlich, was wahrscheinlich auf das Cross-over-Design dieser Studien zurückzuführen ist. L-OHP plus 5-FU/LV ist zudem häufig wirksam bei 5-FU-resistenten oder 5-FU-refraktären Patienten. Auch in der neoadjuvanten Therapie primär nicht resektabler Leberfiliae beim kolorektalen Karzinom zeigt dieses Zytostatikum in Verbindung mit 5-FU/LV viel versprechende Ergebnisse. Dosislimitierende Toxizität ist eine periphere sensorische Neuropathie, die in der Regel innerhalb weniger Monate nach Absetzen der Substanz reversibel ist. Gastrointestinale Toxizitäten werden als geringfügig eingestuft. Im Vergleich zu den bislang beim kolorektalen Karzinom angewandten Substanzen zeichnet sich L-OHP nicht nur durch ein differentes Wirkspektrum aus, sondern eröffnet wegen Wirkungssynergismus und gering ausgeprägter Hämatotoxizität Kombinationsmöglichkeiten mit zahlreichen Zytostatika. Zusammenfassend sind die therapeutischen Möglichkeiten beim kolorektalen Karzinom durch die Entwicklung von L-OHP wesentlich erweitert worden.

The role of oxaliplatin in the therapy for advanced colorectal carcinoma

Preclinical models and numerous phase I to III trials have demonstrated the efficacy of oxaliplatin (l-OHP) for colorectal carcinoma. In previously untreated patients, response rates with l-OHP plus 5-fluorouracil and leucovorin (5-FU/LV) have been shown to be more than twice as high as compared with 5-FU/LV alone, and progression-free intervals have been significantly increased. Nevertheless, overall-survival was similar in both treatment arms, that was possibly due to the cross-over-design of these studies. Moreover, the combination regimens with l-OHP and 5-FU/LV often have shown activity in 5-FU-resistant or 5-FU- refractory patients. Furthermore, treatment of previously unresectable liver metastases from colorectal carcinoma with l-OHP in combination with 5-FU/LV has provided promising results. Dose-limiting toxicity is a peripheral sensory neuropathy, that was found to be mostly completely reversible within a few months. Gastrointestinal toxicities have been demonstrated to be mild. Compared to other anticancer drugs currently used in the treatment for colorectal carcinoma, l-OHP not only shows a different mechanism of action but displays synergistic anti-tumor activity as well as minimal hematologic toxicity making this agent interesting for combination chemotherapy protocols. In conclusion, the development of l-OHP has essentially increased the therapeutical possibilities of treatment for colorectal carcinoma.

Schlüsselwörter

Chemotherapie - Kolorektales Karzinom - Oxaliplatin - Übersicht

Key words

Chemotherapy - Colorectal Carcinoma - Oxaliplatin - Review

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