Is a perioperative chemotherapy based on FOLFOX and Cetuximab (K-RAS wild-type) associated with a higher rate of postoperative complications in patients with resectable colorectal liver metastases as compared to only adjuvant FOLFOX and chemotherapy? Are there any differences for disease free survival between periand postoperative treatment in patients with \>3 liver metastases or at least one metastasis \> or = 5 cm in diameter?
In recent years chemotherapy based on FOLFOX and cetuximab has become a standard treatment in patients with colorectal liver metastases. Recently, the analysis of the CELIM trial reported response rates of 70% in patients with initially unresectable colorectal liver metastases treated with FOLFOX + Cetuximab. 46% of the patients had their metastases R0 or R1 resected or a ablation by radiofrequency with an overall 34% R0 resection rate. In recent studies, adjuvant chemotherapy with FOLFOX leads to a prolongation of disease free survival after successful resection of colorectal liver metastases, but there is not sufficient data concerning a perioperative regimen. In only one study of Nordlinger et al. a trend in progression-free survival could be reached in patients receiving a perioperative FOLFOX-therapy, but without reaching statistical significance. Furthermore those patients displayed a significantly higher rate of postoperative complications and morbidity. Although the advantages of perioperative treatment are not proven, this concept has become more and more popular in recent years, mainly because of a lack of guidelines. Thus the aim of our study is to compare the complication rate of both therapeutical concepts. Furthermore, secondary objectives (disease-free survival, overall survival, resection rates, response rates, toxicities and quality of life) will be used to estimate the efficacy, feasibility, and safety of both regimens. Perioperative treatment probably has a better efficacy in patients with high tumor burden (\>3 liver metastases or one metastasis \> or = 5 cm in diameter) with effect on disease free survival and will be investigated in a subgroup analysis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
16
surgery -\> 4-8 weeks rest -\> 24 weeks FOLFOX + cetuximab
12 weeks FOLFOX + cetuximab -\> 4 weeks rest -\> surgery -\> 4-8 weeks rest -\> 12 weeks FOLFOX + cetuximab
Department of Surgery, University Hospital Aachen
Aachen, North Rhine-Westphalia, Germany
Clavien score (> grade 1)
The first primary objective of the study is to compare the postoperative complication rate according to Clavien score (\> grade 1) of a perioperative chemotherapy with a postoperative regimen
Time frame: 1 year
Disease free survival
A second primary objective of the study is to compare for the patient subgroup with \>3 liver metastases or at least one metastasis \> or = 5 cm in diameter the median disease free survival.
Time frame: 1 year
Secondary objectives
Secondary Objectives: * To compare the overall disease-free survival. * To compare the overall survival. * To compare operation, resection and R0 rates. * To compare the safety and chemotherapy-associated toxicity (NCI-CTC V4.0) * To compare the effect of a perioperative therapy on healthrelated quality of life (EORTC QLQ-C30 + QLQ-LMC21). * To compare the number of cycles, dose intensity and dose modifications applied. * To evaluate the response rate (RECIST V1.1 no confirmation of response needed) after preoperative chemotherapy. * Resected liver mass
Time frame: 5 years
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