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Colon Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage IV and Recurrent Colon Cancer Treatment

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Other local ablative techniques that have been used to manage liver metastases include embolization and interstitial radiation therapy.[29,30] Patients with limited pulmonary metastases, and patients with both pulmonary and hepatic metastases, may also be considered for surgical resection, with 5-year survival possible in highly-selected patients.[12,31,32]

Adjuvant chemotherapy

The role of adjuvant chemotherapy after potentially curative resection of liver metastases is uncertain.

Evidence (adjuvant chemotherapy):

  1. A trial of hepatic arterial floxuridine and dexamethasone plus systemic fluorouracil (5-FU) and leucovorin compared with systemic 5-FU plus leucovorin alone showed improved 2-year progression-free survival (PFS) (57% vs. 42%, P = .07) and overall survival (OS) (86% vs. 72%, P = .03) but did not show a significant statistical difference in median survival, compared with systemic 5-FU therapy alone.
    • Median survival in the combined therapy arm was 72.2 months versus 59.3 months in the monotherapy arm (P = .21).[33][Level of evidence: 1iiA]
  2. A second trial preoperatively randomly assigned 109 patients who had one to three potentially resectable colorectal hepatic metastases to either no further therapy or postoperative hepatic arterial floxuridine plus systemic 5-FU.[34] Of those randomly assigned patients, 27% were deemed ineligible at the time of surgery, which left only 75 patients evaluable for recurrence and survival.
    • While liver recurrence was decreased, median or 4-year survival was not significantly different.

Further studies are required to evaluate this treatment approach and to determine if more effective systemic combination chemotherapy alone may provide similar results compared with hepatic intra-arterial therapy plus systemic treatment.

Intra-arterial chemotherapy

Hepatic intra-arterial chemotherapy with floxuridine for liver metastases has produced higher overall response rates but no consistent improvement in survival when compared with systemic chemotherapy.[2,35,36,37,38,39] A meta-analysis of the randomized studies, which were all done in the era when only fluoropyrimidines were available for systemic therapy, did not demonstrate a survival advantage.[40]

Several studies show increased local toxic effects with hepatic infusional therapy, including liver function abnormalities and fatal biliary sclerosis.

Treatment of Stage IV and Recurrent Colon Cancer

  • Surgery.
  • Chemotherapy and targeted therapy.
  • Second-line chemotherapy.

Surgery

Treatment of patients with recurrent or advanced colon cancer depends on the location of the disease. For patients with locally recurrent and/or liver-only and/or lung-only metastatic disease, surgical resection, if feasible, is the only potentially curative treatment.

Chemotherapy and targeted therapy

Currently, there are eight active and approved drugs for patients with metastatic colorectal cancer that are used alone and in combination with other drugs:

Drug combinations described in this section include the following:

  • The Arbeitsgemeinschaft Internische Onkologie (AIO) or German AIO regimen (folic acid, 5-FU, and irinotecan):
    • Irinotecan (100 mg/m2) administered as a 2-hour infusion on day 1; leucovorin (500 mg/m2) administered as a 2-hour infusion on day 1; followed by 5-FU (2,000 mg/m2) intravenous (IV) bolus via ambulatory pump administered for a period of 24 hours on a weekly basis four times a year (52 weeks).
  • The CAPOX regimen:
    • Capecitabine (1,000 mg/m2) twice a day on days 1 through 14 plus oxaliplatin (70 mg/m2) on days 1 and 8 every 3 weeks.
  • The Douillard regimen (folic acid, 5-FU, and irinotecan):
    • Irinotecan (180 mg/m2) administered as a 2-hour infusion on day 1; leucovorin (200 mg/m2) administered as a 2-hour infusion on day 1 and day 2; followed by a loading dose of 5-FU (400 mg/m2) IV bolus, then 5-FU (600 mg/m2) via ambulatory pump administered for a period of 22 hours on day 1 and day 2 every 2 weeks.
  • The FOLFOX4 regimen (oxaliplatin, leucovorin, and 5-FU):
    • Oxaliplatin (85 mg/m2) administered as a 2-hour infusion on day 1; leucovorin (200 mg/m2) administered as a 2-hour infusion on day 1 and day 2; followed by a loading dose of 5-FU (400 mg/m2) IV bolus, then 5-FU (600 mg/m2) administered via ambulatory pump for a period of 22 hours on day 1 and day 2 every 2 weeks.
  • The FOLFOX6 regimen (oxaliplatin, leucovorin, and 5-FU):
    • Oxaliplatin (85–100 mg/m2) administered as a 2-hour infusion on day 1; leucovorin (400 mg/m2) administered as a 2-hour infusion on day 1; followed by a loading dose of 5-FU (400 mg/m2) IV bolus on day 1, then 5-FU (2,400–3,000 mg/m2) administered via ambulatory pump for a period of 46 hours every 2 weeks.
  • The FOLFIRI regimen (folic acid, 5-FU, and irinotecan):
    • Irinotecan (180 mg/m2) administered as a 2-hour infusion on day 1; leucovorin (400 mg/m2) administered as a 2-hour infusion on day 1; followed by a loading dose of 5-FU (400 mg/m2) IV bolus administered on day 1, then 5-FU (2,400–3,000 mg/m2) administered via ambulatory pump for a period of 46 hours every 2 weeks.
  • The FUFOX regimen:
    • Oxaliplatin (50 mg/m2) plus leucovorin (500 mg/m2) plus 5-FU (2,000 mg/m2) as a 22-hour continuous infusion on days 1, 8, 22, and 29 every 36 days.
  • The FUOX regimen:
    • Continuous infusion 5-FU (2,250 mg/m2) 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.
  • The IFL (or Saltz) regimen (irinotecan, 5-FU, and leucovorin):
    • Irinotecan (125 mg/m2), 5-FU (500 mg/m2) IV bolus, and leucovorin (20 mg/m2) IV bolus administered weekly for 4 out of 6 weeks.
  • The XELOX regimen:
    • Oral capecitabine (1,000 mg/m2) twice a day for 14 days plus oxaliplatin (130 mg/m2) on day 1 every 3 weeks.
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