~ Elizabeth Jones, CRNP

On September 22, 2015 the U.S. Food and Drug Administration approved Lonsurf, a combination of two drugs, trifluridine and tipiracil, for patients with advanced (metastatic) colorectal cancer whose disease has progressed after treatment with standard therapies or have had limited therapeutic options to treat their disease. Trifluridine is a nucleoside metabolic inhibitor, and tipiracil is a thymididine phosphorylase inhibitor. Following uptake into cancer cells, the drug is incorporated into DNA, interferes with DNA synthesis, and inhibits cell proliferation.

Lonsurf is a new therapeutic option for patients with advanced (metastatic) colorectal cancer previously treated chemotherapy and biologic therapy with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy regimens, an anti-VEGF biologic therapy, and if RAS wild-type, an anti-EGFR therapy.

The approval is based on an international, randomized, double-blind, placebo-controlled study conducted in patients with previously treated metastatic colorectal cancer. A total of 800 patients were randomized 2:1 to receive Lonsurf (N=534) pluS best supportive care (BSC) or matching placebo (N=266) plus BSC. Randomization was stratified by KRAS status (wild-type vs. mutant), time since diagnosis of first metastasis (<18 months vs. ≥ 18 months), and region (Japan vs. US, Europe and Australia). Patients received 35 mg/m2 Lonsurf or matching placebo orally twice daily after meals on Days 1 - 5 and 8 – 12 of each 28-day cycle until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall survival (OS) and an additional efficacy outcome measure was progression-free survival (PFS). A statistically significant improvement in overall survival and progression-free survival were demonstrated in patients in the Lonsurf plus BSC arm compared to those who received placebo plus BSC. Median OS (months) was 7.1 versus 5.3 (p<0.001). PFS was 88% versus 94%, respectively (p<0.001).

The most common side effects of treatment with Lonsurf are low blood counts, which can sometimes be severe, including: anemia (low red blood cell count), neutropenia (low white blood cell count), and thrombocytopenia (low platelet count). Other common side effects are weakness, fatigue, nausea, decreased appetite, diarrhea, vomiting, abdominal pain, and fever.

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