Capecitabine for locally advanced and metastatic colorectal cancer: A review

Table 3 Randomized trials that compare oxaliplatin plus capecitabine with oxaliplatin plus 5-fluorouracil ± folinic acid in metastatic colorectal cancer

Trial	Arms	Patients No.	PFS (mo)	OS (mo)	RR (%)	Severe toxicity≥grade 3
FOCA trial[31]	XELOX: (oxaliplatin 130 mg/m2 on day 1 and capecitabine 2000 mg/m2 per day for 14 d, repeating every 21 d) pviFOX: (protracted fluorouracil intravenous infusion plus oxaliplatin)	62 56	7 9	NR NR	43 48	Less diarrhea (8 vs 18%) and stomatitis (19 vs 29 %) in XELOX arm
US TREE-1[32]	XELOX: as above bFOL: (oxaliplatin 85 mg/m2 on day 1 and fluorouracil 500 mg/m2 plus folinic acid 20 mg/m2 intravenously on days 1 and 8, every 2 wk) mFOLFOX: (oxaliplatin 85 mg/m2, folinic acid 350 mg/m2, fluorouracil 400 mg/m2 bolus and 2400 mg/m2 46-h infusion on day 1)	49 50 49	5.9 6.9 8.7	17.2 17.9 17.6	27 20 41	Less neutropenia (15%) but more dehydration (27%) with XELOX
German trial[33]	CAPOX: (oxaliplatin 70 mg/m2 on days 1 and 8, and capecitabine 2000 mg/m2 per day for 2 wk, recycling every 3 wk) FUFOX: (fluorouracil 2000 mg/m2 infused over 24 h, folinic acid 500 mg/m2 and oxaliplatin 50 mg/m2 infused over 2 h)	241 233	7.1 8.0	16.8 18.8	48 54	More skin toxicity (10% vs 4%) with CAPOX
Spanish trial[34]	XELOX: as above FUOX: (fluorouracil 2250 mg/m2 infused over 48 h once a week plus oxaliplatin 85 mg/m2 twice a week)	171 171	8.9 9.5	18.1 20.8	37 46	Less diarrhea (14% vs 24%) with XELOX
French trial[35]	XELOX: as above FOLFOX6: (oxaliplatin 100 mg/m2, folinic acid 200 mg/m2 infused over 2, fluorouracil 400 mg/m2 bolus and 2400 mg/m2 infused over 48 h)	156 150	8.8 9.3	19.9 20.5	39 46	Less neutropenia (5% vs 47%), febrile neutropenia (0% vs 6%) and neuropathy (11% vs 25%) with XELOX
NO16966 trial[36]	XELOX: as above FOLFOX4: (oxaliplatin 85 mg/m2 on day 1, folinic acid 100 mg/m2, fluorouracil 400 mg/m2 bolus and 600 mg/m2 infused over 22 h)	317 317	7.3 7.7	NR NR	37 39	Less neutropenia (7% vs 43%) but more diarrhea (20% vs 11%) and Hand Foot Syndrome (6% vs 1%) with XELOX
COFFEE trial[38]	OXXEL: (oxaliplatin 100 mg/m2 on day 1 and capecitabine 2000 mg/m2 per day from day 1 to day 11 every 2 wk) OXAFAFU: (oxaliplatin 85 mg/m2 infused over 2 h on day 1, folinic acid 250 mg/m2 infused over 2 h on day 1, fluorouracil 850 mg/m2 bolus on day 2)	158 164	6.2 6.3	16.0 17.1	34 33	Less neutropenia (10% vs 27%) and febrile neutropenia (6% vs 13%), more gastric symptoms (8% vs 3%) and diarrhea (13% vs 8%) with OXXEL

PFS: Progression free survival; OS: Overall survival; RR: Response rate; NR: Not recorded.