Colon Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage III Colon Cancer Treatment
Chemotherapy regimens after 2000
Capecitabine is an oral fluoropyrimidine that undergoes a three-step enzymatic conversion to 5-FU with the last step occurring in the tumor cell. For patients with metastatic colon cancer, two studies have demonstrated the equivalence of capecitabine to 5-FU-leucovorin.[22,23]
For patients with stage III colon cancer, capecitabine provides equivalent outcome to intravenous 5-FU and leucovorin.
- A multicenter European study compared capecitabine (1,250 mg/m2) administered twice daily for days 1 to 14, then given every 21 days for eight cycles against the Mayo Clinic schedule of 5-FU and low-dose leucovorin for patients with stage III colon cancer.
- The study demonstrated that DFS at 3 years is equivalent for patients receiving capecitabine or 5-FU-leucovorin (hazard ratio [HR], 0.87; P < .001).[Level of evidence: 1iiDii]
- Hand-foot syndrome and hyperbilirubinemia were significantly more common for patients receiving capecitabine, but diarrhea, nausea or vomiting, stomatitis, alopecia, and neutropenia were significantly less common.
- Of patients receiving capecitabine, 57% required a dose modification.
- For patients with stage III colon cancer in whom treatment with 5-FU-leucovorin is planned, capecitabine is an equivalent alternative.
Oxaliplatin has significant activity when combined with 5-FU-leucovorin in patients with metastatic colorectal cancer.
- In the 2,246 patients with resected stage II or stage III colon cancer in the completed Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC [NCT00275210]) study, the toxic effects and efficacy of FOLFOX4 were compared with the same 5-FU-leucovorin regimen without oxaliplatin administered for 6 months. Based on results from the MOSAIC trial, adjuvant FOLFOX4 demonstrated prolonged OS for patients with stage III colon cancer compared with patients receiving 5-FU-leucovorin without oxaliplatin.
- The preliminary results of the study with 37 months of follow-up demonstrated a significant improvement in DFS at 3 years (77.8% vs. 72.9%, P = .01) in favor of FOLFOX4. When initially reported, there was no difference in OS.[Level of evidence: 1iiDii]
- Further follow-up at 6 years demonstrated that the OS for all patients (both stage II and stage III) entered into the study was not significantly different (OS = 78.5% vs. 76.0%; HR, 0.84; 95% confidence interval [CI], 0.71–1.00). On subset analysis, the 6-year OS in patients with stage III colon cancer was 72.9% in the patients receiving FOLFOX4 and 68.7% in the patients receiving 5-FU-leucovorin (HR, 0.80; 95% CI, 0.65–0.97, P = .023).[Level of evidence: 1iiA]
- Patients treated with FOLFOX4 experienced more frequent toxic effects consisting mainly of neutropenia (41% >grade 3) and reversible peripheral sensorial neuropathy (12.4% >grade 3).
FOLFOX has become the reference standard for the next generation of clinical trials for patients with stage III colon cancer.