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Drug therapy of cancer in the colon and rectum

Drug therapy is under updating.

Operable colon cancer

After surgery for stage II colon cancer, adjuvant chemotherapy is not recommended  as standard treatment. It is recommended to consider chemotherapy in cases of tumor perforation before or after surgery, or when there was too few (≤ 8) examined lymph nodes in the resected specimen. 

After surgery for colon cancer with lymph node metastases in the resected specimen (stage III), adjuvant chemotherapy is recommended  starting 4-6 weeks after surgery. 

  • For patients < 70 years, standard treatment is chemotherapy (5-FU and calcium folinate combined with oxaliplatin (FLOX regimens)). Twelve cycles are given every 14 days for 6 months. 
  • 5-FU with calcium folinate (FLV cycles) is often given to patients 70-75 years, or to patients with low tolerance for chemotherapy. Twelve cycles are given for 6 months.  Another possible alternative is oral capecitabine for 8 cycles in 3 week intervals. 
  • Individual treatment is considered for patients 75-80 years of age.   

Operable rectal cancer

In locally advanced rectal cancer, which is about 10-15% of rectal cancer patients, who based on MRI have short margins (≤ 3 mm) to the surgical dissection plane (mesorectal fascia), chemoradiation therapy is recommended before surgery.  

  • Radiation therapy 50 Gy over 5 weeks.
  • Radiation therapy combined with concomitant radiation sensitizing chemotherapy, either oral capecetabine 5 out of 7 days of the week or Nordic FLV 3 courses intravenously, during the period of radiation therapy.

Preoperative radiation therapy reduces the risk for local recurrence by half, and this risk is reduced additionally by addition of concomitant 5-FU. Combination regimens during radiation therapy are currently not known to have an additional positive effect. The benefit of adjuvant chemotherapy after surgery for rectal cancer is not as strongly documented as for colon cancer, and is not recommended as standard treatment in Norway

Primary resectable and potentially resectable liver metastases

In patients without other disease than liver metastases from colon or rectal cancer, there is still discussion regarding the benefit of chemotherapy in association with surgery for liver metastases. In  some selected patients, there appears to be benefit from perioperative chemotherapy (FLOX/FOLFOX) in 6 cycles before and 6 cycles after liver surgery. The indication for this should be evaluated by a multidisciplinary team.

Primary inoperable liver metastases that may be potentially operable after chemotherapy, are recommended to consider combination chemotherapy, possibly with the addition of antibodies  to achieve the highest possible response rate.

Palliative drug therapy

For inoperable disease or distant metastases, chemotherapy may have a palliative effect and prolong survival. The purpose of treatment is then not to cure the disease, but rather to hinder growth and progression. 

As first line treatment, 5-FU/calcium folinate combined with oxaliplatin or irinotecan are considered equivalent regimens based on response and survival data. Different variants of these regimens are available, but the most common in Norway is FLV with oxaliplatin (FLOX) or irinotecan (FLIRI). The general health status of the patient and symptoms may influence the choice of chemotherapy due to differing side effect profiles. In elderly patients with comorbidity, Nordic FLV may be considered.  

If the disease progresses, it is often neccessary to change the chemotherapy regimen.

Bevacizumab is an angiogenesis inhibitor antibody that binds to vascular endothelial growth factor (VEGF) and may be used as first-line treatment of metastatic colon and rectal cancer in patients expected to tolerate this treatment. It is important to be aware of potential side effects such as thromboembolistic conditions, hypertension, and delayed wound healing.

Cetuximab or panitumumab are antibodies against growth factor receptor EGFR. It is shown that these drugs are effective only in KRAS wild-type tumors. This may be appropriate to consider in palliative third-line drug therapy.

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