FDA Approves a Combination Chemotherapy for Advanced Colorectal Cancer

The U.S. Food and Drug Administration approval provides a new option for patients whose disease is no longer responding to other treatments.

A new combination of drugs was approved by the U.S. Food and Drug Administration (FDA) for treating certain patients with colorectal cancer.

The drug combination, which is formulated together in a single pill called Lonsurf, is intended for patients with advanced colorectal cancer whose disease has worsened despite treatment with chemotherapy and a biological therapy. The combination of drugs was shown to extend overall survival for patients in a double-blind, placebo-controlled, phase III clinical trial.

Advances against colorectal cancer are urgently needed because even though screening has helped dramatically reduce incidence and mortality rates, the disease remains the second-leading cause of cancer-related death in the United States.

The new pill, which was called TAS-102 before being renamed Lonsurf, contains two drugs – called trifluridine and tipiracil that work together to exert an anticancer effect. Trifluridine is the cytotoxic chemotherapy component of TAS-102, while tipiracil prevents rapid breakdown of trifluridine, thereby keeping trifluridine at high enough levels in the body for it to have an effect.

Trifluridine is a chemotherapy drug that works by causing damage to DNA, which can ultimately trigger the death of cells. Researchers believe that the main way in which the trifluridine component of TAS-102 damages DNA is through its similarity to the basic building blocks of DNA. As a result of this similarity, it can be incorporated into DNA after it has been modified by a natural cellular process called phosphorylation. However, because it is not a true DNA building block, its incorporation results in abnormal, or damaged, DNA.

Other drugs with similarity to DNA building block, such as fluorouracil, have been a mainstay of cancer chemotherapy for decades. In the phase III clinical trial that led to the FDA approval of TAS-102, the new combination chemotherapy pill extended survival even for those patients who had colorectal cancer that was no longer responding to treatment with fluorouracil-containing treatments.

With several ongoing clinical trials evaluating TAS-102 as a treatment for other types of cancer, we will likely learn more about the potential for this agent to benefit a wider group of patients in the near future.

The FDA approval was rendered on September 22, 2015.