Artikel
Hepatic-arterial infusion of the monoclonal antibodies cetuximab and bevacizumab results in a significant reduction of tumor growth of colorectal liver metastases
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Autoren
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Jens Sperling
- Universitätsklinikum des Saarlandes, Klinik für Allgemeine Chirurgie, Viszeral-, Gefäß- und Kinderchirurgie, Homburg/Saar
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David Brandhorst
- Universitätsklinikum des Saarlandes, Institut für Klinisch-Experimentelle Chirurgie, Homburg/Saar
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Anna Benz
- Universitätsklinikum des Saarlandes, Institut für Klinisch-Experimentelle Chirurgie, Homburg/Saar
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Christian Ziemann
- Universitätsklinikum des Saarlandes, Klinik für Allgemeine Chirurgie, Viszeral-, Gefäß- und Kinderchirurgie, Homburg/Saar
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Otto Kollmar
- Klinik für Plastische-, Hand und Wiederherstellungschirurgie, Klinik für Allgemeine Chirurgie, Viszeral-, Gefäß- und Kinderchirurgie, Homburg/Saar
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Martin K. Schilling
- Universitätsklinikum des Saarlandes, Klinik für Allgemeine Chirurgie, Viszeral-, Gefäß- und Kinderchirurgie, Homburg a.d. Saar
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Michael D. Menger
- Universitätsklinikum des Saarlandes, Institut für Klinisch-Experimentelle Chirurgie, Homburg a.d. Saar
| Veröffentlicht: | 20. Mai 2011 |
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Gliederung
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Introduction: Systemic chemotherapy (SYS) remains the gold standard in the treatment of irresectable colorectal liver metastases. The addition of the monoclonal antibodies (mAb) cetuximab or bevacizumab has led to further improvement of outcome. However, a hepatic-arterial infusion (HAI) as locoregional chemotherapy might be capable of additionally increasing the antitumor effect of these agents. Herein, we studied whether mAb alone or in combination with irinotecan given as HAI, exert an increased antitumor effect compared to SYS.
Materials and methods: WAG/RIJ-rats (300g bw) randomized in 8 groups (n=6 each) underwent a hepatic injection of CC531 cells to induce colorectal liver metastases. Tumor growth was measured after ten days by using three dimensional ultrasound. Thereafter, animals underwent either HAI or SYS of cetuximab and bevacizumab (CE+BE), irinotecan alone (IR), or the combination of all three drugs (CE+BE+IR). Animals of the control groups received saline solution (Sham). Three days after this treatment tumor growth was measured again and histological and immunohistochemical analysis were performed.
Results: In both controls tumor volume was found significantly increased (Sham HAI: +46.9±22.1%; Sham SYS +57.1±14.4%). Irinotecan alone was not capable of inhibiting tumor growth (IR HAI: +60.9±13.2%; IR SYS: +51.5±8.0%). In contrast, HAI of cetuximab plus bevacizumab significantly (p<0.05) reduced tumor growth compared to SYS (CE+BE HAI: +16.7±7.7%; CE+BE SYS: +82.5±19.1%). The combination of the mAb with irinotecan yielded an even more pronounced inhibitory effect on tumor growth when given as HAI (CE+BE+IR HAI: +8.7±12.8%; CE+BE+IR SYS: +104.1±7.4%). Immunohistochemical analysis of caspase-3 showed an increased tumor cell apoptosis when HAI was used. Moreover analysis of PECAM-1 showed a decreased tumor vascularization after HAI.
Conclusion: Our study demonstrates that HAI of cetuximab plus bevacizumab is effective to inhibit tumor growth. This effect is even more pronounced in combination with irinotecan. Systemic application of these agents cannot achieve comparable effects.
