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Zentralbl Chir 2003; 128(2): 87-94
DOI: 10.1055/s-2003-37760
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© Georg Thieme Verlag Stuttgart · New York

Prospective Pilot Study of Neoadjuvant Chemotherapy with 5-Fluorouracil, Folinic Acid and Oxaliplatin in Resectable Liver Metastases of Colorectal Cancer. Analysis of 42 Neoadjuvant Chemotherapies*

Prospektive Pilotstudie zur neoadjuvanten Chemotherapie mit 5-Fluorouracil, Folinsäure und Oxaliplatin bei resektablen Lebermetastasen kolorektaler Karzinome. Analyse von 42 neoadjuvanten ChemotherapienM. Lorenz1 , E. Staib-Sebler1 , C. Gog1 , D. Proschek1 , K.-W. Jauch2 , K. Ridwelski3 , W. Hohenberger4 , H.-J. Gassel5 , U. Lehmann 6 , K.-H. Vestweber7 , W. Padberg8 , K. Zamzow9 , H.-H. Müller9
  • 1Dept. of General and Vascular Surgery, Johann-Wolfgang-Goethe-University Frankfurt
  • 2Clinic of Surgery of the University Regensburg
  • 3Clinic of Surgery, Otto-von-Guericke University, Magdeburg
  • 4Clinic of Surgery of the Friedrich-Alexander University, Erlangen
  • 5Clinic of Surgery of the Julius-Maximilians University, Würzburg
  • 6Clinic of General Surgery, St. Georg Hospital, Leipzig
  • 7Clinic of General Surgery, Klinikum Leverkusen, Leverkusen
  • 8Clinic of General Surgery of the Justus-Liebig University, Gießen
  • 9Institute of Medical Biometry and Epidemiology, Philipps University, Marburg
*Herrn Prof. Dr. Albrecht Encke zur Emeritierung gewidmet
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Publication History

Publication Date:
11 March 2003 (online)

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Abstract

Purpose: Since there are currently no data available from a prospective trial, the primary objective of this prospective study was to investigate whether the rate of R0-liver resections without morbidity would be at least 50 % in patients with neoadjuvant chemotherapy for colorectal liver metastases.

Patients and methods: 42 patients were treated with a biweekly FOLFOX regimen. Chemotherapy consisted of a 2-hour infusion of folinic acid (FOL) 500 mg/m2, followed by a 24-hour infusion of 5- fluorouracil (F) 2 000 mg/m2 daily for two days. Oxaliplatin (OX) 85 mg/m2 was given simultaneously with FOL. Treatment allocation was randomized with either 3 or 6 cycles for the final 30 patients. A liver resection was performed 2 to 5 weeks after the final infusion.

Results: An objective response was observed in 20 of 42 patients (response rate was 27 % higher after 6 cycles). Liver resection (R0) could be performed in 34 patients. Postoperative complications were reported in 14 patients (13 occurring within 30 days after resection) and severe complications in 5 cases (including two deaths after extended resection). Liver failure and persistent biliary fistula were the most frequently documented complications. There was no relevant difference in safety criteria between 3 and 6 applications.

Conclusion: The use of neoadjuvant chemotherapy in resectable liver metastases induced significant remissions without increasing morbidity. The rate of severe complications and cases of no R0-resection in this study was 31 % and was with that significantly lower than 50 % (95 % CI 17.6 %-47.1 %). The risk to the patient is therefore acceptable when undergoing neoadjuvant treatment in a prospective intergroup trial.

Zusammenfassung

Ziel der Untersuchung: Derzeit existieren keine prospektiven Daten zur neoadjuvanten Chemotherapie vor Resektion kolorektaler Lebermetastasen. Primäres Studienziel war es deshalb in dieser prospektiven Studie zu überprüfen, ob bei dieser Therapie eine Rate von mindestens 50 % R0-Resektionen ohne Morbidität erzielt werden kann.

Methodik: 42 Patienten wurden mit einem 14-tägigen FOLFOX-Regime behandelt. Die Chemotherapie beinhaltete eine 2-h-Infusion mit Folinsäure (FOL) 500 mg/m2/d, gefolgt von einer 24-h-Infusion mit 5-Fluorouracil (F) 2 000 mg/m2/d jeweils über zwei Tage. Oxaliplatin (OX) 85 mg/m2 wurde simultan mit FOL am ersten Therapietag verabreicht. Die letzten 30 Patienten wurden in entweder 3 oder 6 Zyklen der Chemotherapie randomisiert. Die Leberresektion wurde 2 bis 5 Wochen nach der letzten Chemotherapie durchgeführt.

Ergebnisse: Ein objektives Ansprechen wurde in 20 von 42 Patienten beobachtet. Bei der Durchführung von 6 Zyklen war die Ansprechrate um 27 % höher. 34 Patienten konnten R0-leberreseziert werden. Über postoperative Komplikationen wurde bei 14 Patienten (13 innerhalb von 30 Tagen nach Resektion) und über schwere Komplikationen in 5 Fällen (inklusive 2 Todesfälle nach erweiterter Resektion) berichtet. Leberversagen und persistierende Gallefisteln wurden am häufigsten dokumentiert. Relevante Unterschiede hinsichtlich der Sicherheitskriterien zwischen 3 und 6 Applikationen ergaben sich nicht.

Diskussion: Eine neoadjuvante Chemotherapie bei resektablen Lebermetastasen führt zu einer signifikanten Remission ohne Anstieg der Morbidität nach Resektion. Die Rate an schweren Komplikationen und R1- oder R2-Resektionen betrug 31 % und war damit signifikant niedriger als 50 % (95 % CI 17,6 %-47,1 %). Das Risiko der Durchführung einer neoadjuvanten Chemotherapie innerhalb einer prospektiven Intergroup-Studie ist somit für den Patienten akzeptabel.

Key words

Neoadjuvant chemotherapy - liver metastases - colorectal

Schlüsselwörter

Neoadjuvante Chemotherapie - Lebermetastasen - Kolorektal

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Prof. Dr. Matthias Lorenz

Department of General and Vascular Surgery

Johann-Wolfgang-Goethe University

Theodor-Stern-Kai 7

60590 Frankfurt am Main

Phone: 0 69/6 31 43 46

Fax: 0 69/6 31 43 47

Email: gog@em.uni-frankfurt.de

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