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.
OBJECTIVE
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.


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) 2000 mg/m2 daily for two days. Oxaliplatin (OX) 85 mg/m 2 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.


CONCLUSIONS
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.
Lorenz
Matthias
M
Department of General and Vascular Surgery, Johann-Wolfgang-Goethe-University Frankfurt, Frankfurt au Main. gog@em.uni-frankfurt.de
Staib-Sebler
Elsbeth
E
Gog
Christiane
C
Proschek
D
D
Jauch
K-W
KW
Ridwelski
K
K
Hohenberger
W
W
Gassel
H-J
HJ
Lehmann
Ute
U
Vestweber
K-H
KH
Padberg
W
W
Zamzow
Karin
K
Müller
H-H
HH
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds; D010865:Pilot Projects; D011183:Postoperative Complications / Q000139:chemically induced / Q000401:mortality; D011446:Prospective Studies; D015996:Survival Rate
D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil