• © 2007 by American Society of Clinical Oncology

In Reply

We thank Dr Kokudo and colleagues for their contribution to this important issue. They experience the same difficulties as other collaborative groups by facing slow recruitment when conducting a trial with a nontreated control group. Indeed, all patients do not fulfill all the inclusion criteria that are necessary for designing randomized trials. In addition, practitioners and/or patients do not want to be in the untreated groups. The inclusion rate of the UMIN-CTR:C000000013 trial is approximately 17% of original candidates, which is more than the expected objective of the French Institute of Cancer, which recommended at least 10% of cancer patients be included in trials.

In fact, and as in the Japanese experience, no similar randomized trial with a surgery only control group is now registered in the international Current Controlled Trials meta-register. Despite the weaknesses of the FFCD ACHBT AURC trial, it represents the best currently available evidence on this topic. Since the pending question seemed essential, our collaborative group kept active on the study and the follow-up of patients for more than 10 years in order to achieve the study.¹ The chemotherapy used was less active and more toxic than currently used regimens, but its beneficial use on disease-free survival was still demonstrated. The recently communicated results of a combined analysis of our trial and another intergroup trial confirmed a benefit of postoperative chemotherapy on disease-free survival and overall survival.²

Considering the results of this study and other available studies of adjuvant treatment after liver resection for liver metastases of colorectal origin, we now believe that the evidence is strong enough to recommend adjuvant chemotherapy for all resected patients. The French practice guidelines have now evolved by implementing these conclusions.

New trials now focus on the best chemotherapy regimen using new agents such as oxaliplatin, irinotecan, or targeted biotherapies (bevacizumab, cetuximab), and on the relevance of preoperative chemotherapy. For the latter question, one has to wait for the results of the last study with a surgery only group initiated by the European Organisation for the Research and Treatment of Cancer.³ Only such an international collaborative group could achieve sufficient recruitment given all the difficulties described by Kokudo and colleagues.