FDA Approves New Oral Medication for the Treatment of Refractory Metastatic Colorectal Cancer

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Richard Pazdur, MD

[Approval of trifluridine/tipiracil (Lonsurf)] is a testament to the FDA’s commitment to work with companies to develop new drugs in disease areas where unmet needs remain.

—Richard Pazdur, MD

The U.S. Food and Drug Administration (FDA) has approved trifluridine/tipiracil (Lonsurf) for patients with metastatic colorectal cancer who have been previously treated with chemotherapy and biologic therapy and are no longer responding to treatment.

Mechanism of Action

The new oral agent is a combination of trifluridine and tipiracil hydrochloride. Trifluridine is the active component of the combination and is directly incorporated into DNA, leading to DNA dysfunction. However, when trifluridine is taken orally it is largely degraded to an inactive form. Tipiracil hydrochloride prevents the degradation of trifluridine.

“The past decade has brought a new understanding around colorectal cancer, in how we can both detect and treat this often devastating disease,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “But there are many patients who still need additional options, and [this recent] approval is a testament to the FDA’s commitment to work with companies to develop new drugs in disease areas where unmet needs remain.”

Study Details

The efficacy and safety of trifluridine/tipiracil were evaluated in an international, randomized, double-blind study involving 800 patients with previously treated metastatic colorectal cancer.1

Study participants received trifluridine/tipiracil plus best supportive care, or placebo plus best supportive care until their disease worsened or side effects became intolerable. The primary endpoint of the study was overall survival and the secondary endpoint was progression-free survival. Patients treated with trifluridine/tipiracil lived an average of 7.1 months compared to 5.3 months for those treated with placebo. On average, the time to disease progression was 2 months for patients on trifluridine/tipiracil compared to 1.7 months for patients receiving placebo.

Safety and Toxicity

The most common side effects of treatment with trifluridine/tipiracil are anemia, neutropenia or thrombocytopenia, physical weakness, fatigue, nausea, decreased appetite, diarrhea, vomiting, abdominal pain, and fever.

The FDA recommends that health-care providers obtain complete blood counts prior to starting each treatment cycle of trifluridine/tipiracil and monitor patients throughout treatment, as the drug may cause a severe decrease in blood cell and platelet production.

Health-care providers are also encouraged to advise women of potential risks to developing fetuses when taking trifluridine/tipiracil. Women who are taking trifluridine/tipiracil should not breastfeed.

Colorectal cancer is the third most common nonskin cancer in men and women in the United States, according to the National Cancer Institute. While it is still the second leading cause of cancer-related death in the United States, over the past 10 years the number of colorectal cancer cases and related deaths have decreased, due in part to screenings, such as colonoscopies. ■


Yoshino T, Mayer R, Falcone A, et al: Results of a multicenter, randomized, double-blind, phase III study of TAS-102 vs placebo, with best supportive care, in patients with metastatic colorectal cancer refractory to standard therapies (RECOURSE). Ann Oncol 25(suppl 2):ii114, 2014.  Presented at ESMO 16th World Congress on Gastrointestinal Cancer, June 25–28, 2014, Barcelona.