Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal cancer patients: results of the Southern Italy Cooperative Oncology study 0401

Abstract

Purpose Oxaliplatin combined with either Xuorouracil/ leucovorin (OXAFAFU) or capecitabine (OXXEL) has a demonstrated activity in metastatic colorectal cancer patients. We aimed at comparing these two regimens in terms of response rate (RR), safety, progression-free survival (PFS), and quality of life (QoL) of patients. Methods A total of 322 patients with metastatic colorectal cancer were randomized to receive biweekly: oxaliplatin 100 mg/m 2 i.v. on day 1, capecitabine 1,000 mg/m 2 orally twice daily from day 1 to day 11 (OXXEL); or oxaliplatin 85 mg/m 2 i.v. on day 1; 6S-leucovorin 250 mg/m 2 i.v. and Xuorouracil 850 mg/m 2 i.v. on day 2 (OXAFAFU). Results Eleven complete and 42 partial responses were registered with OXXEL (RR = 34%); six complete and 48 partial responses were obtained with OXAFAFU (RR = 33%) (P = 0.999). Severe adverse events were less frequent (32 vs. 43%) with OXXEL, which also reduced the occurrence of severe neutropenia (10 vs. 27%) and febrile neutropenia (6 vs. 13%), but produced more gastric side eVects (8 vs. 3%) and diarrhea (13 vs. 8%). QoL did not diVer across the two arms. Median PFS was 6.6 months in the OXXEL, and 6.5 months in the OXAFAFU arm (HR = 1.12, P = 0.354). Median overall survival was 16.0 and 17.1 months (HR = 1.01, P = 0.883). Conclusions OXXEL and OXAFAFU regimens were equally active in metastatic colorectal cancer. The choice should be based on patient preference and on pharmacoeconomic evaluations.

Capecitabine-based chemotherapy for metastatic colorectal cancer

“…Two of the ten trials Kohne et al 2008) included other treatment arms, in addition to the two arms considered for the meta-analysis. In combination settings, capecitabine dose was 1,000 mg/m 2 .bid d 1-11 in one trial (Comella et al 2009), 1,000 mg/m 2 .bid d 1-14 in six trials Diaz-Rubio et al 2007;Kohne et al 2008;Martoni et al 2006;Porschen et al 2007;Rothenberg et al 2008), and 1,000 mg/m 2 .bid d 2-15 in one trial (Skof et al 2009). …”

“…1), ten eligible trials Comella et al 2009;Diaz-Rubio et al 2007;Hoff et al 2001;Kohne et al 2008;Martoni et al 2006;Porschen et al 2007;Rothenberg et al 2008;Skof et al 2009;Van Cutsem et al 2001) were identified, and the respective electronic databases were obtained for all of them. The quality scores of the RCTs were assessed according to the Jadad scale (Jadad et al 1996) and ranged from 2 to 4 (5-point scale), with a mean of 3.3.…”

The clinical effectiveness and cost-effectiveness of cetuximab (review of technology appraisal no. 176) and panitumumab (partial review of technology appraisal no. 240) for previously untreated metastatic colorectal cancer: a systematic review and economic evaluation

“…Of the studies included in Amgen's NMA [n = 21, reported in 22 publications 28 [78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94] The reason for their exclusion was that they did not evaluate the effectiveness of the interventions in the RAS WT population. In addition to the abstracts for the OPUS 33 and CRYSTAL 34 trials included in the Amgen NMA, the Assessment Group identified the full publications.…”

Capecitabine versus 5-fluorouracil in colorectal cancer: where are we now?

“…Available quality-of-life data suggest that there are no differences between capecitabine and 5-FU-based regimens [71,72]. A study by Liu et al [73] suggests that patients prefer oral chemotherapy, provided that efficacy is not compromised.…”