Lower incidence of adverse events about capecitabine and oxaliplatin from the GOIM 2802 study: a commentary

© Digestive Medicine Research. All rights reserved. Dig Med Res 2020 | http://dx.doi. org/10.21037/dmr-20-100 The GOIM 2802 study is a randomized phase II trial to estimate the efficacy of bi-weekly XELOX (capecitabine plus oxaliplatin) with bevacizumab compared with FOLFOX4 [a bi-weekly bolus and infusional fluorouracil (FU) with folinic acid (FA) plus oxaliplatin] with bevacizumab in first-line therapy for patients with metastatic colorectal cancer (1). Generally, FOLFOX4 is a conventional treatment regimen for metastatic colorectal cancer (2). However, the continuous administration of FU requires the insertion of central venous catheters and infusion pumps, which inconvenient for patients and increases the risk of infections and thromboembolism. Capecitabine, an oral fluoropyrimidine, has been known to be a convenient and well-tolerated agent with equal efficacy to infusional FU with FA (3). The efficacy of XELOX with or without bevacizumab had been demonstrated in several phase III trials for the first-line setting of metastatic colorectal cancer (4-6). Updated survival data from the NO16966 phase III trial showed that survival benefit was similar between XELOX and FOLFOX4 (7). Considering the result of pivotal phase III trials, the standard dose of XELOX regimen consists of a 2-hour infusion of oxaliplatin 130 mg/m on day 1 plus oral capecitabine starting dose of 1,000 mg/m twice daily for 2 weeks, repeated every 3 weeks. Until now, this tri-weekly XELOX regimen has been described in various regional guidelines as one of the treatment options in the first-line setting and frequently used for adjuvant chemotherapy, especially for stage III colorectal cancer (8-10). In terms of effectiveness for the first-line setting, although the efficacy of tri-weekly XELOX and infusional FU plus oxaliplatin (e.g., FOLFOX4 and FUOX) are almost similar, the profile of adverse events are different (6,11). Based on NO16966 study which showed that XELOX with or without bevacizumab is non-inferior to FOLFOX with or without bevacizumab in the first-line treatment for mCRC, tri-weekly XELOX demonstrated more grade 3 hand-foot syndrome (6% vs. 1%) and diarrhea (19% vs. 11%) than FOLFOX4. In contrast, FOLFOX4 was associated with more grade 3 or 4 neutropenia (44% vs. 7%), and febrile neutropenia (6.3% vs. 3.8%) than tri-weekly XELOX (6). Hand-foot syndrome, known as palmar-plantar erythrodysesthesia syndrome, acral erythema, and more recently grouped with the so-called toxic erythema of chemotherapy syndromes, is a relatively common skin reaction to fluoropyrimidine (e.g., capecitabine, FU, and S-1), pegylated liposomal doxorubicin and docetaxel (12). In particular, capecitabine is known to induce severe handfoot syndrome, i.e., all grade hand-foot syndrome was occurred in 50–60% (grade 3 was approximately 25%) of patients treated with capecitabine alone (recommended dosage: 1,250 mg/m twice daily) (12). Hand-foot syndrome is rarely life-threatening but can considerably decrease the quality of life of the patient, causing the need for a dose Editorial Commentary