Chemotherapy of metastatic XXXX .

@entity1 @entity901 @entity4181 @entity2600 @entity416 @entity5 @entity984 @entity470 @entity2359 @entity14 @entity1487
Without treatment, @entity1 with inoperable or metastatic @entity14 have a median life expectancy of about 8 months. The following article is an update of our 2005 review of chemotherapy regimens used in metastatic @entity14 , based on the standard Prescrire methodology. In 2005, the de Gramont protocol, based on @entity1487 (always combined with @entity4181 ) plus either @entity901 (Folfox protocol) or @entity2600 (Folfiri protocol), was the standard first-line chemotherapy in this setting. Four trials comparing monotherapy versus combination therapy in previously untreated @entity1 showed that initial @entity1487 (or @entity1487 precursor) monotherapy, followed by the Folfox or Folfiri protocol in case of failure, was not associated with shorter overall survival. Two trials compared first-line treatment with the Folfiri regimen versus the Folfoxiri regimen ( @entity1487 + @entity901 + @entity2600 ). One of these studies showed an increase in median survival with the Folfoxiri protocol (24 versus 17 months), but at a cost of greater @entity2359 . The only tangible advantage of @entity416 and tegafur, two oral @entity1487 precursors, is their convenience of use. Pemetrexed was less effective and more toxic than the Folfiri protocol in one trial. Bevacizumab and panitumumab have yielded disappointing results in previously untreated @entity1 . Neither of these monoclonal antibodies has yet been shown to improve overall survival. Three trials have assessed the addition of cetuximab to combinations consisting of @entity1487 or @entity416 plus @entity901 or @entity2600 . In two of these trials, the median survival time of @entity1 whose @entity5 carried the wild-type @entity984 gene was about 3 months longer in the cetuximab arms, although the increase was statistically significant in only one trial. Cetuximab had no impact on survival time in the third trial. In two trials, an anti- @entity470 antibody (panitumumab or cetuximab) reduced median survival when added to bevacizumab in previously untreated @entity1 . When progression occurs after treatment with the Folfiri protocol (or equivalent), a combination of the Folfox protocol and bevacizumab seems to increase median survival time by about 2 months versus Folfox alone, but it is also more toxic. In @entity1 who progress after receiving the @entity1487 + @entity901 combination (Folfox) or the @entity1487 + @entity2600 combination (Folfiri), neither panitumumab nor cetuximab has been shown to provide a clinically meaningful increase in overall survival. It remains to be shown whether these drugs are more effective in @entity1 with the wild-type @entity984 gene than in @entity1 with @entity984 mutations. In early 2010, the standard cytotoxic drugs for treatment of metastatic @entity14 are @entity1487 (combined with @entity4181 ), @entity901 and @entity2600 . Initial combination therapy may be beneficial when the metastases are borderline operable. When the metastases are inoperable and are unlikely to become operable after chemotherapy, it seems best to begin treatment with single-agent @entity1487 (+ @entity4181 ) or @entity416 . The use of monoclonal antibodies in first-line treatment of @entity1 with @entity14 is not justified. Further trials of these drugs are warranted as second-line treatment for @entity1 with @entity984 wild-type @entity5 .
