Table 6.
Metastatic colorectal cancer treatment: SIGN recommendations
| Quality of evidences(SIGN) | Recommendation | Strength 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 |
| A | The 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 |
| A | Capecitabine 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 |
| A | Capecitabine 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 |
| A | If no contraindications, bevacizumab can be used in combination with first-line chemotherapy.10–15 49 50 | Strong for |
| A | If 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 |
| B | Bevacizumab beyond progression in combination with chemotherapy can be a treatment option.28 29 | Conditional for |
| A | A 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 |
| A | Cetuximab 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 |
| B | Cetuximab 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 |
| A | Panitumumab (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 |
| A | In 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 |
| A | The 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 |
| B | A sequential and less toxic strategy can be considered in case of indolent disease.44 45 | Conditional for |
| B | FOLFOXIRI plus bevacizumab should be considered as first-line treatment in BRAF mutated and fit patients.58 | Strong for |
| B | To reduce treatment-related toxicity a ‘stop-and-go’ strategy or a less intensive treatment can be considered.59–61 | Conditional for |
| B | In 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.