For the first time, researchers have shown that a chemotherapy regimen of capecitabine plus oxaliplatin (CAPOX) is as safe and effective as infusional 5-fluorouracil/folinic acid plus oxaliplatin (FUFOX) in the first-line treatment of metastatic colorectal carcinoma (MCRC). The findings are reported at the 2nd ESMO Scientific & Educational Conference (ESEC) in Budapest, Hungary.
"We conducted this phase III study because the combination of oral capecitabine and oxaliplatin showed promising effects in different phase II studies. The idea of this study was to look whether CAPOX can replace the standard treatment of iv. 5-FU/folinic acid in patients with MCRC", said lead author Dr. Hendrik-Tobias Arkenau, from Clinic Bremen East in Germany.
From 2002 to 2004, the authors randomly assigned 476 patients who had not undergone previous chemotherapy to receive either FUFOX (5-fluorouracil (5-FU) 2000mg/m2 24h infusion, folinic acid 500mg/m2, oxaliplatin 50mg/m2 d1,8,15,22; q5 wks) or CAPOX (capecitabine 1000mg/m2 bid d1-14, oxaliplatin 70mg/m2 d1 and 8; q3 wks).
So far, based on an analysis of 2541 treatment cycles (1026 FUFOX, 1515 CAPOX), both regimens are comparably toxic and showed similar response rates (ITT-RR: 50% FUFOX and 47% CAPOX, p=NS).
Median length of time without progression of disease was 34.7 weeks in the FUFOX arm and 30.3 weeks in the CAPOX arm, respectively, a difference that was not statistically different (p=0.1), the authors found. Additionally, both treatment arms showed similar overall survival, FUFOX 74.9 weeks and CAPOX 70.9 weeks, p=0.72.
The authors conclude that CAPOX shows comparable efficacy and toxicity profiles compared to the FUFOX regimen in patients chemonaive MCRC.
"This study is important for patients because the CAPOX regimen is more convenient to administer. Patients will appreciate needing to come only twice in three weeks as outpatients to receive the 2 hourly oxaliplatin dose. Especially in the palliative setting of MCRC, patients gain more autonomy and improved quality of life," Dr. Arkenau said.
"We hope that oral capecitabine plus oxaliplatin will become the new standard treatment in first-line treatment for patients with metastatic colorectal carcinoma."
Commenting on the study, Professor Hans Joachim Schmoll of Martin-Luther-Universität Halle-Wittenberg in Germany said the results of the trial "are of major importance for the clinical routine, at least for those patients who would like to avoid intravenous infusional protocols, ports and pumps."
The 5-FU-infusion in combination with cytostatic agents like oxaliplatin or irinotecan in patients with colorectal cancer is complicated and needs support and a pump for the patient, he said. This is a cause of major discomfort, meaning it is important to investigate alternatives substituting the infusion of 5-FU by oral agents.
"This study for the first time shows that an oral based Cap/Ox regimen is able to substitute for the complex intravenous 5-FU 2-drug- or 3-drug-combination in colorectal cancer. Large trials are underway to definitely answer this question with several thousand patients; however, the results of these studies will not be available before 2006," Professor Schmoll said.