Conjecture about Hand-Foot Syndrome in CLASSIC Trial.

Dear Editor-in-Chief

It is widely known that the CLASSIC trial (1) was the first international phase III study to investigate the effectiveness of adjuvant chemotherapy over surgery alone after D2 dissection of gastric cancer in an Asian population. In this trial, the incidence of hand-foot syndrome (HFS) was 1%. Many reports have suggested that HFS may be a valuable tool with which to evaluate and monitor the efficacy of capecitabine in patients with colorectal cancer and breast cancer (2–4). It is undetermined that HFS as a tool to evaluate and monitor the drug efficacy can obtain the same results in postoperative stomach cancer patients. The use of existing data from the CLASSIC trial to identify an association between HFS and the efficacy of capecitabine in patients with stomach cancer is considered viable. However, many objective difficulties stand in the way.

The incidence of HFS in the CLASSIC trial was 19%, and 1% of patients had grade III to IV HFS (1). The lower incidence of grade III to IV HFS in this study was due to the education of patients in terms of avoiding severe HFS. For example, if patients had grade II HFS, they were advised to skip several doses of capecitabine.

Previous studies on HFS involved patients with metastatic disease (2–4). However, the CLASSIC trial involved patients with potentially curable disease. The only parameter of efficacy was relapse. Therefore, it is not easy to correlate the severity of HFS with relapse. An additional compounding factor is that oxaliplatin was used.

Above all, the CLASSIC trial is not the most accurate means of identifying the association between HFS and the efficacy of capecitabine in patients with stomach cancer. More superior clinical trials should be performed in the future.