Table 1. Synopsis of studies comparing capecitabine containing regimens to 5-FU containing regimens. Included are the dosing regimens, PFS statistics, median OS statistics, and toxicities observed in the treatment arms.
| Study | German AIO group (19) | Spanish group (20) | French study (21) | Tree-1-US study (22) | GOAM-Italian study (23) |
|---|---|---|---|---|---|
| Dosing regimen CAPOX/XELOX based treatment arm | CAPOX: oxaliplatin 70 mg/m2 2-hour infusion days 1 and 8 every 3 weeks, capecitabine 1,000 mg/m2 bid orally days 1-14 every 3 weeks | XELOX: oral capecitabine 1,000 mg/m2 bid for 14 days plus oxaliplatin 130 mg/m2 on day 1 every 3 weeks | XELOX: 2-hour iv of oxaliplatin 130 mg/m2 on day 1 plus oral capecitabine 1,000 mg/m2 twice daily on days 1-14 every 3 weeks | CapeOx: oxaliplatin 130 mg/m2 iv on day 1 and capecitabine 1,000 mg/m2 orally twice daily on days 1-15 every 3 weeks | XELOX: oxaliplatin as noted below and oral capecitabine at the dose of 1,000 mg/m2 bid from the 1st to the 14th day |
| Dosing regimen FU + OX based treatment arm | FUFOX: oxaliplatin 50 mg/m2 2-hour infusion, folinic acid 500 mg/m2 2-hour infusion, FU 2,000 mg/m2 22-hour infusion; days 1, 8, 15, and 22 every 5 weeks | FUOX: FU 2,250 mg/m2 diluted in saline administered by civ during 48 hours on days 1, 8, 15, 22, 29, and 36, plus oxaliplatin 85 mg/m2 on days 1, 15, and 29 every 6 weeks | FOLFOX6: 2-hour iv of oxaliplatin 100 mg/m2 followed by a 2-hour infusion of LV 400 mg/m2 followed by 5-FU 400 mg/m2 given as an intravenous bolus injection and then 5-FU 2,400-3,000 mg/m2 as a 46-hour civ every 2 weeks | mFOLFOX6: oxaliplatin 85 mg/m2 iv with LV 350 mg iv over 2 hours plus FU 400 mg/m2 iv bolus and 2,400 mg/m2 civ over 46 hours every 2 weeks bFOL: oxaliplatin 85 mg/m2 iv on days 1 and 15 and LV 20 mg/m2 iv over 10-20 minutes followed by FU 500 mg/m2 iv push on days 1, 8, and 15 every 4 weeks |
PVIFOX: dexamethasone 20 mg in 100 cc of saline by the intravenous (iv) route in 15 min, granisetron 3 mg in 100 cc of saline iv in 15 min, oxaliplatin at the dose of 130 mg/m2 in 500 cc of 5% glucose solution iv in 2 hours and, at the end, 5-FU at the dose of 250 mg/m2/daily in civ from the 1st to the 21st day |
| Number of patients in CAPOX treatment arm | 242 | 171 | 144 | 48 | 62 |
| Number of patients in FU + OX treatment arm | 234 | 171 | 140 | 50 (bFOL) & 49 (mFOLFOX) | 56 |
| PFS in treatment arms CAPOX/XELOX vs. FU + OX (months) | 7.1 vs. 8.0 (P=0.117) | 8.9 vs. 9.5 (P=0.153) | 8.8 vs. 9.3 | 5.9 (CapeOx) vs. 6.9 (bFOL) vs. 8.7 (mFOLFOX) | 9.0 vs. 7.0 |
| OS in treatment arms CAPOX/XELOX vs. FU + OX (months) | 16.8 vs. 18.8 (P=0.26) | 18.1 vs. 20.8 (P=0.145) | 19.9 vs. 20.5 | 17.2 (CapeOx) vs. 17.9 (bFOL) vs. 17.6 (mFOLFOX) | NA |
| RR in treatment arms CAPOX/XELOX vs. FU + OX | 48% vs. 54% | 37% vs. 46% | 42% vs. 46% | 27% (CapeOx) vs. 20% (bFOL) vs. 41% (mFOLFOX) | 43% vs. 48% |
| Toxicity in treatment arms CAPOX/XELOX vs. FU + OX | Nausea, vomiting, and diarrhea were similar in both treatment groups. Only HFS grade 2/3 was significantly higher in the CAPOX arm (P=0.028) | Lower rates of grade 3/4 diarrhea (14% vs. 24%, P=0.027) and grade 1/2 mucositis (28% vs. 43%, P=0.005), with higher rates of grade 1/2 hyperbilirubinemia (37% vs. 21%, P=0.001) and grade 1/2 hand-foot syndrome (14% vs. 5%, P=0.009) with XELOX arm vs. FUOX arm, respectively | XELOX arm had significantly more grade 3/4 thrombocytopenia (12% vs. 5%) and diarrhea (14% vs. 7%), but significantly less grade 3/4 neutropenia (5% vs. 47%), febrile neutropenia (0% vs. 6%) and neuropathy (11% vs. 26%) than FOLFOX6 patients | Grade 3/4 treatment-related adverse events during the first 12 weeks of treatment were 59%, 36%, and 67% for mFOLFOX6, bFOL, and CapeOx, respectively. CapeOx toxicity included grade 3/4 diarrhea (31%) and dehydration (27%) | Grade 3/4 diarrhea was observed in 14.0% vs. 8.2%, grade 3 stomatitis in 3.7% vs. 0%, and grade 3 neurotoxicity in 18.5% vs. 24.6%, when comparing vs. PVIFOX vs. XELOX |
AIO, Arbeitsgemeinschaft Internistische Onkologie; iv, intravenous infusion; 5-FU, 5-fluorouracil; LV, leucovorin; civ, continuous intravenous infusion; PFS, progression free survival; OS, overall survival; NA, not available; RR, response rate; HFS, hand foot syndrome.