Table 6

Metastatic colorectal cancer treatment: SIGN recommendations

Quality of evidences(SIGN)RecommendationStrength of recommendation
C RAS status must be evaluated for the decision of treatment strategy for metastatic disease.18 Strong for
D* BRAF status should be evaluated for the decision of treatment strategy for metastatic disease.Conditional for
AThe combination of 5-fluorouracil (continuous infusion is preferable) and oxaliplatin and/or irinotecan must be used in patients deemed fit for a combination treatment (the combination with anti-VEGF or anti-EGFR monoclonal antibodies is preferable). For unfit patients the option is fluoropyrimidine±bevacizumab.10–15 19–22 44–50 Strong for
ACapecitabine can substitute for monotherapy with 5-fluorouracil+folinic acid. When a monotherapy is indicated, capecitabine is the first option, preferably with bevacizumab.10 50 Strong for
ACapecitabine can be used in combination with oxaliplatin.51–53 Capecitabine plus irinotecan, due to increased toxicity, should be used only if there are contraindications to infusional 5-fluorouracil.54 55 Strong for
AIf no contraindications, bevacizumab can be used in combination with first-line chemotherapy.10–15 49 50 Strong for
AIf no contraindications, bevacizumab can be used in combination with second-line chemotherapy in patients not treated with bevacizumab as first-line treatment.30 Strong for
BBevacizumab beyond progression in combination with chemotherapy can be a treatment option.28 29 Conditional for
AA second-line treatment must be always considered in fit patients.
A third- and fourth-line treatment can be considered in several cases.56 57
Strong for
ACetuximab can be used in RAS wild-type patients in combination with irinotecan-based regimens (irrespective of treatment line) or as monotherapy in advanced lines.19 36 Strong for
BCetuximab can be associated with first-line oxaliplatin-based treatment. In this case, continuous infusion of 5-fluorouracil without bolus is preferable.21 23 24 Strong for
APanitumumab (anti-EGFR) can be used as monotherapy in advanced lines, in RAS wild-type patients not previously treated with cetuximab or after a severe infusion reaction to cetuximab.37 Strong for
AIn RAS wild-type patients, panitumumab can be used in combination with first-line FOLFOX or FOLFIRI,20 22 and with second-line FOLFIRI.33 Strong for
AThe combination of aflibercept with second-line FOLFIRI in patients previously treated with an oxaliplatin-based treatment (with or without a biological drug) can be an option.31 Conditional for
BA sequential and less toxic strategy can be considered in case of indolent disease.44 45 Conditional for
BFOLFOXIRI plus bevacizumab should be considered as first-line treatment in BRAF mutated and fit patients.58 Strong for
BTo reduce treatment-related toxicity a ‘stop-and-go’ strategy or a less intensive treatment can be considered.59–61 Conditional for
BIn patients pretreated or not considered candidates for all the available drugs, regorafenib can be an option.38 TAS-102 could be a further option in this setting. 39 Conditional for
  • *Panel opinion.

  • ‡At the moment authorised but not refundable in Italy.

  • EGFR, epidermal growth factor receptor; FOLFIRI, folinic acid, 5-fluorouracil and irinotecan; FOLFOX, folinic acid, 5-fluorouracil and oxaliplatin; SIGN, Scottish Intercollegiate Guidelines Network; VEGF, vascular endothelial growth factor.