Four-Drug Regimen Not Beneficial in Colorectal Cancer

Adding cetuximab to capecitabine, oxaliplatin and bevacizumab leads to poorer outcomes

WEDNESDAY, Feb. 4 (HealthDay News) -- In patients with metastatic colorectal cancer, the addition of cetuximab to capecitabine, oxaliplatin and bevacizumab is associated with significantly reduced progression-free survival and a lower quality of life, according to a report published in the Feb. 5 issue of the New England Journal of Medicine.

Jolien Tol, M.D., of the Radboud University Nijmegen Medical Center in Nijmegen, the Netherlands, and colleagues randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin and bevacizumab, or the same regimen plus weekly cetuximab.

After a median follow-up of 23 months, the researchers found that the four-drug group had a significantly reduced progression-free survival time (9.4 months versus 10.7 months), a trend toward reduced median overall survival (19.4 months versus 20.3 months), and lower quality-of-life scores compared to the three-drug group. They also found that the addition of cetuximab was associated with a decreased progression-free survival for tumors with a mutated KRAS gene.

"The findings…serve as a reminder that antitumor activity observed in preclinical and also uncontrolled clinical contexts may not be validated when examined in randomized trials," states the author of an accompanying editorial. "Furthermore, the data suggest that combining multiple forms of targeted therapies may not be analogous to combining different types of cytotoxic chemotherapy, presumably because of subtle interactions in intracellular signaling. Finally, these results underscore the fundamental importance of subjecting hypotheses to carefully conducted clinical trials. As was observed in this situation, more is not always better."

Several authors of the study and editorial disclosed financial support from pharmaceutical companies.

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