First-line chemotherapy in metastatic colorectal cancer: new approaches and therapeutic algorithms. Always hit hard first?

Abstract

Management of advanced colorectal cancer has been revolutionized in recent years by the introduction of new drugs and expanded surgical indications. This review focuses on what should be considered to define the optimal approach to each patient, in particular with regard to the intensiveness of first-line chemotherapy. Final results of clinical trials exploring different ways of facing metastatic colorectal cancer have been recently published. On the one hand, the possibility of improving the outcome intensifying first-line chemotherapy by the concomitant use of three cytotoxics has been demonstrated. On the other hand, although in differently selected populations, 'staged strategies' provided similar survival results to up-front combinations. As it is no longer possible to define a standard treatment for all patients, we discuss the principles that should guide our decision-making process. In particular, we distinguish five categories of patients: with immediately resectable metastases; with 'marginally' or 'potentially' resectable metastases; with either never resectable widespread aggressive disease or tumour-related performance status deterioration or both; with never resectable widespread indolent disease and without tumour-related performance status deterioration; at high-risk of toxicity either because of comorbidities or age or both.For each group, the intensity of the first-line chemotherapy is discussed, considering recent data from randomized trials.