FOLFIRI treatment response not related to colorectal cancer classification by gene expression

The current classification system for colorectal cancer, which is based on genetic expression profiles, cannot be used to predict drug responses to FOLFIRI. This conclusion, published as correspondence in Nature Medicine (2014; doi:10.1038/nm.3701), will assist oncologists in making better-informed decisions regarding how to treat their colorectal cancer patients in the clinic.

This analysis was conducted by a team from the Spanish National Cancer Research Centre (CNIO), formed by members from the Gastrointestinal Cancer Clinical Research Unit and the Structural Computational Biology Group. The study was led by Manuel Hidalgo, MD, PhD, Director of the Clinical Research Programme at CNIO, and it is in response to previous work published in the same journal in March (2014; doi:10.1038/nm.3175).

The previous work had analyzed gene expression profiles and designed a classification for colon cancer based on five subtypes. One subtype, known as the stemlike subtype, was associated with a better drug response to FOLFIRI, which is the standard treatment for this tumor type. Specifically, in a 21-patient group, seven were classified as this subtype, of whom five (70%) exhibited a positive response to FOLFIRI. The authors therefore concluded that the classification based on gene expression profiles is directly related to the drug response.

To confirm their conclusion, CNIO researchers, following their protocol, classified 10 patients who had previously been treated at the clinic with this therapy. Three of these patients belonged to the stemlike subtype but none of them responded to treatment with FOLFIRI. Patients belonging to the other subtypes, on the other hand, showed a response to the treatment.

"We have analyzed the data from the original work and we see that it is not statistically significant, even when we increase the sample size to ours. The number of patients included in the original study is insufficient to establish a positive correlation between classification of the tumor based on gene expression profiles and sensitivity to FOLFIRI," warned researcher Raquel Martínez, MD, the article's first author.

"Genetic classification of tumors is key to enhancing our understanding of cancer mechanisms and to make personalized therapeutic decisions," explained Hidalgo. "In this case, however, the data must be confirmed by further research studies to keep an erroneous correlation from leading doctors to prescribe inadequate treatments in the clinic."

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