Treatment Option Overview for Colon Cancer
|Stage (TNM Staging Criteria)||Standard Treatment Options|
|Stage 0 Colon Cancer||Surgery|
|Stage I Colon Cancer||Surgery|
|Stage II Colon Cancer||Surgery|
|Stage III Colon Cancer||Surgery|
|Stage (TNM Staging Criteria)||Treatment Options|
|Treatment of Liver Metastasis||Surgery|
|Treatment of Stage IV and Recurrent Colon Cancer||Surgery|
|Chemotherapy and targeted therapy|
Primary Surgical Therapy
Standard treatment for patients with colon cancer has been open surgical resection of the primary and regional lymph nodes for localized disease.
Evidence (laparoscopic techniques):
- A multicenter, prospective, randomized, noninferiority trial (NCCTG-934653) compared laparoscopic-assisted colectomy (LAC) with open colectomy in 872 patients.
- At a median follow-up of 4.4 years, 3-year recurrence rates (16% LAC vs. 18% open colectomy; hazard ratio [HR] for recurrence, 0.86; 95% confidence interval [CI], 0.63–1.17; P = .32) and 3-year overall survival (OS) rates (86% LAC vs. 85% open colectomy; HR for death in LAC, 0.91; 95% CI, 0.68–1.21; P = .51) were similar in both groups for all stages of disease evaluated. Tumor recurrence in surgical incisions was less than 1% for both groups.[Level of evidence: 1iiA]
- Decreased hospital stay (5 days LAC vs. 6 days open colectomy, P < .001) and decreased use of analgesics were reported in the LAC group. A 21% conversion rate from LAC to open procedure was shown.
- This study excluded patients with locally advanced disease, transverse colon and rectal tumor locations, and perforated lesions. Each of the 66 surgeons participating in the trial had performed at least 20 LACs and were accredited for study participation after independent videotape review assured appropriate oncologic and surgical principles were maintained. The quality-of-life component of this trial was published separately and minimal short-term quality-of-life benefits with LAC were reported.[Level of evidence: 1iiC]
- One small, single-institution randomized study of 219 patients showed that the LAC procedure was independently associated with reduced tumor recurrence on multivariate analysis.[Level of evidence: 1iiB]
Surgery is curative in 25% to 40% of highly selected patients who develop resectable metastases in the liver and lung. Improved surgical techniques and advances in preoperative imaging have allowed for better patient selection for resection.
The potential value of adjuvant chemotherapy for patients with stage II colon cancer is controversial. Pooled analyses and meta-analyses have suggested a 2% to 4% improvement in OS for patients treated with adjuvant fluorouracil (5-FU)–based therapy compared with observation.[8-10] (Refer to the Stage II Colon Cancer Treatment section of this summary for more information.)
Prior to 2000, 5-FU was the only useful cytotoxic chemotherapy in the adjuvant setting for patients with stage III colon cancer. Since 2000, capecitabine has been established as an equivalent alternative to 5-FU and leucovorin. The addition of oxaliplatin to 5-FU and leucovorin has been shown to improve OS compared with 5-FU and leucovorin alone. (Refer to the Stage III Colon Cancer Treatment section of this summary for more information.)
Table 8 describes the chemotherapy regimens used to treat colon cancer.
|Regimen Name||Drug Combination||Dose|
|5-FU = fluorouracil; AIO = Arbeitsgemeinschaft Internistische Onkologie; bid = twice a day; IFL = irinotecan, 5-FU, and leucovorin; IV = intravenous; LV = leucovorin.|
|AIO or German AIO||Folic acid, 5-FU, and irinotecan||Irinotecan (100 mg/m2) and LV (500 mg/m2) administered as 2-hour infusions on d 1, followed by 5-FU (2,000 mg/m2) IV bolus administered via ambulatory pump weekly over 24 h, 4 times a y (52 wk).|
|CAPOX||Capecitabine and oxaliplatin||Capecitabine (1,000 mg/m2) bid on d 1–14, plus oxaliplatin (70 mg/m2) on d 1 and 8 every 3 wk.|
|Douillard||Folic acid, 5-FU, and irinotecan||Irinotecan (180 mg/m2) administered as a 2-h infusion on d 1, LV (200 mg/m2) administered as a 2-h infusion on d 1 and 2, followed by a loading dose of 5-FU (400 mg/m2) IV bolus, then 5-FU (600 mg/m2) administered via ambulatory pump over 22 h every 2 wk on d 1 and 2.|
|FOLFIRI||LV, 5-FU, and irinotecan||Irinotecan (180 mg/m2) and LV (400 mg/m2) administered as 2-h infusions on d 1, followed by a loading dose of 5-FU (400 mg/m2) IV bolus administered on d 1, then 5-FU (2,400–3,000 mg/m2) administered via ambulatory pump over 46 h every 2 wk.|
|FOLFOX4||Oxaliplatin, LV, and 5-FU||Oxaliplatin (85 mg/m2) administered as a 2-h infusion on d 1, LV (200 mg/m2) administered as a 2-h infusion on d 1 and 2, followed by a loading dose of 5-FU (400 mg/m2) IV bolus, then 5-FU (600 mg/m2) administered via ambulatory pump over 22 h every 2 wk on d 1 and 2.|
|FOLFOX6||Oxaliplatin, LV, and 5-FU||Oxaliplatin (85–100 mg/m2) and LV (400 mg/m2) administered as 2-h infusions on d 1, followed by a loading dose of 5-FU (400 mg/m2) IV bolus on d 1, then 5-FU (2,400–3,000 mg/m2) administered via ambulatory pump over 46 h every 2 wk.|
|FOLFOXIRI||Irinotecan, oxaliplatin, LV, 5-FU||Irinotecan (165 mg/m2) administered as a 60-min infusion, then concomitant infusion of oxaliplatin (85 mg/m2) and LV (200 mg/m2) over 120 min, followed by 5-FU (3,200 mg/m2) administered as a 48-h continuous infusion.|
|FUFOX||5-FU, LV, and oxaliplatin||Oxaliplatin (50 mg/m2) plus LV (500 mg/m2) plus 5-FU (2,000 mg/m2) administered as a 22-h continuous infusion on d 1, 8, 22, and 29 every 36 d.|
|FUOX||5-FU plus oxaliplatin||5-FU (2,250 mg/m2) administered as a continuous infusion over 48 h on d 1, 8, 15, 22, 29, and 36 plus oxaliplatin (85 mg/m2) on d 1, 15, and 29 every 6 wk.|
|IFL (or Saltz)||Irinotecan, 5-FU, and LV||Irinotecan (125 mg/m2) plus 5-FU (500 mg/m2) IV bolus and LV (20 mg/m2) IV bolus administered weekly for 4 out of 6 wk.|
|XELOX||Capecitabine plus oxaliplatin||Oral capecitabine (1,000 mg/m2) administered bid for 14 d plus oxaliplatin (130 mg/m2) on d 1 every 3 wk.|
Adjuvant Radiation Therapy
While combined modality therapy with chemotherapy and radiation therapy has a significant role in the management of patients with rectal cancer (below the peritoneal reflection), the role of adjuvant radiation therapy for patients with colon cancer (above the peritoneal reflection) is not well defined. Patterns-of-care analyses and single-institution retrospective reviews suggest a role for radiation therapy in certain high-risk subsets of colon cancer patients (e.g., T4, tumor location in immobile sites, local perforation, obstruction, and residual disease postresection).[11-16]
Evidence (adjuvant radiation therapy):
- Such observations led to the development of a phase III randomized intergroup study designed to test the benefit of adding radiation therapy to surgery and chemotherapy with 5-FU-levamisole for selected high-risk colon cancer patients (e.g., T4; or T3, N1–N2 ascending and/or descending colon).
- This clinical trial closed early secondary to inadequate patient accrual, and analysis of 222 enrolled patients (the original goal was 700 patients) demonstrated no relapse or OS benefit for the group receiving radiation therapy, though the sample size and statistical power were inadequate to exclude benefit.
Adjuvant radiation therapy has no current standard role in the management of patients with colon cancer following curative resection, although it may have a role for patients with residual disease.
- Bokey EL, Moore JW, Chapuis PH, et al.: Morbidity and mortality following laparoscopic-assisted right hemicolectomy for cancer. Dis Colon Rectum 39 (10 Suppl): S24-8, 1996. [PUBMED Abstract]
- Franklin ME Jr, Rosenthal D, Abrego-Medina D, et al.: Prospective comparison of open vs. laparoscopic colon surgery for carcinoma. Five-year results. Dis Colon Rectum 39 (10 Suppl): S35-46, 1996. [PUBMED Abstract]
- Fleshman JW, Nelson H, Peters WR, et al.: Early results of laparoscopic surgery for colorectal cancer. Retrospective analysis of 372 patients treated by Clinical Outcomes of Surgical Therapy (COST) Study Group. Dis Colon Rectum 39 (10 Suppl): S53-8, 1996. [PUBMED Abstract]
- Schwenk W, Böhm B, Müller JM: Postoperative pain and fatigue after laparoscopic or conventional colorectal resections. A prospective randomized trial. Surg Endosc 12 (9): 1131-6, 1998. [PUBMED Abstract]
- Clinical Outcomes of Surgical Therapy Study Group: A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med 350 (20): 2050-9, 2004. [PUBMED Abstract]
- Weeks JC, Nelson H, Gelber S, et al.: Short-term quality-of-life outcomes following laparoscopic-assisted colectomy vs open colectomy for colon cancer: a randomized trial. JAMA 287 (3): 321-8, 2002. [PUBMED Abstract]
- Lacy AM, García-Valdecasas JC, Delgado S, et al.: Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial. Lancet 359 (9325): 2224-9, 2002. [PUBMED Abstract]
- Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. J Clin Oncol 17 (5): 1356-63, 1999. [PUBMED Abstract]
- Gill S, Loprinzi CL, Sargent DJ, et al.: Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J Clin Oncol 22 (10): 1797-806, 2004. [PUBMED Abstract]
- Mamounas E, Wieand S, Wolmark N, et al.: Comparative efficacy of adjuvant chemotherapy in patients with Dukes' B versus Dukes' C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04) J Clin Oncol 17 (5): 1349-55, 1999. [PUBMED Abstract]
- Willett C, Tepper JE, Cohen A, et al.: Local failure following curative resection of colonic adenocarcinoma. Int J Radiat Oncol Biol Phys 10 (5): 645-51, 1984. [PUBMED Abstract]
- Willett C, Tepper JE, Cohen A, et al.: Obstructive and perforative colonic carcinoma: patterns of failure. J Clin Oncol 3 (3): 379-84, 1985. [PUBMED Abstract]
- Gunderson LL, Sosin H, Levitt S: Extrapelvic colon--areas of failure in a reoperation series: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 11 (4): 731-41, 1985. [PUBMED Abstract]
- Willett CG, Fung CY, Kaufman DS, et al.: Postoperative radiation therapy for high-risk colon carcinoma. J Clin Oncol 11 (6): 1112-7, 1993. [PUBMED Abstract]
- Willett CG, Goldberg S, Shellito PC, et al.: Does postoperative irradiation play a role in the adjuvant therapy of stage T4 colon cancer? Cancer J Sci Am 5 (4): 242-7, 1999 Jul-Aug. [PUBMED Abstract]
- Schild SE, Gunderson LL, Haddock MG, et al.: The treatment of locally advanced colon cancer. Int J Radiat Oncol Biol Phys 37 (1): 51-8, 1997. [PUBMED Abstract]
- Martenson JA Jr, Willett CG, Sargent DJ, et al.: Phase III study of adjuvant chemotherapy and radiation therapy compared with chemotherapy alone in the surgical adjuvant treatment of colon cancer: results of intergroup protocol 0130. J Clin Oncol 22 (16): 3277-83, 2004. [PUBMED Abstract]