What are the chemotherapy options for colorectal (colon) cancer?

From the Guidelines

Chemotherapy for colon cancer should typically involve combinations of drugs administered in specific regimens based on cancer stage and patient factors, with FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin) being recommended for 3-6 months after surgery for stage III and high-risk stage II colon cancer. For stage III colon cancer, adjuvant chemotherapy with FOLFOX or CAPOX is recommended, as it has been shown to improve disease-free survival and overall survival compared to 5-FU/LV alone 1. The combination of 5-FU/LV plus oxaliplatin has been found to significantly improve disease-free survival in stage II and III colon cancer and overall survival in stage III colon cancer compared to 5-FU/LV 1.

Chemotherapy Regimens

• FOLFOX is typically given as oxaliplatin 85 mg/m² IV on day 1, leucovorin 400 mg/m² IV on day 1, followed by 5-FU 400 mg/m² IV bolus then 1200 mg/m² continuous infusion over 46-48 hours, repeated every 2 weeks.
• CAPOX is an alternative regimen that has been shown to be at least as effective as, and less toxic than, bolus 5-FU/LV 1.
• For patients who cannot tolerate oxaliplatin, 5-FU/leucovorin or capecitabine monotherapy are alternatives.
• Metastatic colon cancer may require more intensive regimens like FOLFIRI (5-FU, leucovorin, and irinotecan) or FOLFOXIRI (adding irinotecan to FOLFOX), often combined with targeted therapies such as bevacizumab or cetuximab depending on tumor biomarkers.

Treatment Duration and Monitoring

• Treatment duration and specific regimens are tailored based on disease stage, patient performance status, comorbidities, and molecular characteristics of the tumor.
• Regular monitoring of blood counts, liver function, and treatment response is essential.
• The duration of oxaliplatin-containing adjuvant therapy for stage III colon cancer is recommended to be 3-6 months, as shorter duration treatment may confer the same survival advantage as longer duration treatment while reducing the incidence of peripheral sensory neurotoxicity 1.

Side Effects and Considerations

• Common side effects include neuropathy (oxaliplatin), diarrhea (irinotecan), hand-foot syndrome (capecitabine), and myelosuppression.
• The risk of peripheral sensory neurotoxicity with oxaliplatin-based chemotherapy is a consideration, and the dose and duration of oxaliplatin should be adjusted accordingly 1.

From the FDA Drug Label

Avzivi, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first-or second-line treatment of patients with metastatic colorectal cancer (mCRC) Avzivi, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product-containing regimen.

The chemotherapy options for colorectal (colon) cancer include:

• Fluorouracil-based chemotherapy in combination with bevacizumab for first- or second-line treatment
• Fluoropyrimicide-irinotecan-based chemotherapy in combination with bevacizumab for second-line treatment
• Fluoropyrimidine-oxaliplatin-based chemotherapy in combination with bevacizumab for second-line treatment 2

From the Research

Chemotherapy Options for Colorectal Cancer

• The chemotherapy options for colorectal cancer include:
  • 5-fluorouracil (5-FU) with or without oxaliplatin 3
  • Gemcitabine, oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) (GOLF regimen) 4
  • Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer 5
  • Cetuximab, bevacizumab, and 5-fluorouracil/leucovorin vs. FOLFOX-bevacizumab 6
  • Infusional 5-fluorouracil (5-FU), leucovorin, and oxaliplatin, plus biweekly cetuximab as first-line treatment in patients with metastatic colorectal cancer 7

Efficacy of Chemotherapy Regimens

• The GOLF regimen has shown promising results in the treatment of advanced colorectal cancer, with a response rate of 41% and a median time to progression of 7.26 months 4
• The addition of oxaliplatin to 5-FU regimens has been shown to improve disease-free survival in patients with stage II or III colon cancer 5
• The combination of biweekly cetuximab with FOLFOX-6 has been shown to be well tolerated and have a manageable safety profile for the first-line treatment of KRAS wild-type metastatic colorectal cancer, with a response rate of 70% and a median progression-free survival of 13.8 months 7

Safety and Tolerability of Chemotherapy Regimens

• The most frequent side effect of the GOLF regimen was grade I-II haematological toxicity 4
• The addition of oxaliplatin to 5-FU regimens has been associated with an increased incidence of febrile neutropenia and grade 3 sensory neuropathy 5
• The combination of biweekly cetuximab with FOLFOX-6 has been shown to be well tolerated, with no increase in FOLFOX-6 toxicity 7