The Appraisal Committee has prepared a Final Appraisal Determination on the use of Avastin and Erbitux in metastatic colorectal cancer and submitted it to the Institute.

The main recommendations made are as follows:


Avastin ( Bevacizumab ) in combination with 5-FluoroUracil plus Folinic Acid, with or without Irinotecan, is not recommended for the first-line treatment of metastatic colorectal cancer.

Erbitux ( Cetuximab ) in combination with Irinotecan is not recommended for the second-line or subsequent treatment of metastatic colorectal cancer.

People currently receiving Bevacizumab or Cetuximab should have the option to continue therapy until they and their consultants consider it appropriate to stop.


The management of metastatic colorectal cancer is mainly palliative and involves a combination of treatments ( such as palliative surgery, chemotherapy and radiation ), symptom control and psychosocial support.
The aim is to improve both the duration and quality of the individual’s remaining life.
Clinical outcomes such as overall survival, response and toxicity are important, but alternative outcomes such as progression-free survival, quality of life, convenience, acceptability and patient choice are also important.

The most frequent site of metastatic disease is the liver. In up to 50% of patients with metastatic disease, the liver may be the only site of spread.
For these patients surgery provides the only chance of longer-term survival.
Approximately 10% of patients with metastatic colorectal cancer present with potentially resectable liver metastases and for approximately 14% chemotherapy may render unresectable liver metastases operable.

Individuals with metastatic disease who are sufficiently fit ( normally those with World Health Organization performance status 2 or better ) are usually treated with active chemotherapy as first- or second-line therapy.

First-line active chemotherapy options include infusional 5-FluoroUracil plus Folinic Acid or Leucovorin ( Calcium Folinate ) ( 5-FU/FA, 5-FU/LV ), Oxaliplatin plus infusional 5-FU/FA ( FOLFOX ), and Irinotecan plus infusional 5-FU/FA ( FOLFIRI ).
Oral analogues of 5-FU ( Capecitabine and Tegafur with Uracil ) may also be used instead of infusional 5-FU.
For those patients first receiving FOLFOX, Irinotecan may be a second-line treatment option, whereas for patients first receiving FOLFIRI, FOLFOX may be a second-line treatment option.
Patients receiving 5-FU/FA or oral therapy as first-line treatment may receive treatment with FOLFOX and Irinotecan as second-line and subsequent therapies.

Survival estimates for patients with metastatic colorectal cancer receiving best supportive care are approximately 6 months.
The use of infusional 5-FU/FA can increase survival to approximately 10 -12 months, whereas combinations of FOLFIRI followed by FOLFOX, or FOLFOX followed by Irinotecan, have been reported to increase survival to 20 -21 months.

Source: NICE, 2006


XagenaMedicine2006