A case in which TAS-102 produced disease control without severe adverse events in a patient with recurrent colorectal cancer and dihydropyrimidine dehydrogenase deficiency
Author(s):
Ryo Nakanishi*, Atsuko Tsutsui, Hiroto Tanaka, Kohei Mishima, Chie Hagiwara, Takahiro Ozaki, Kazuharu Igarashi, Satoru Ishii, Nobuhiko Okamoto, Kenji Omura, Go Wakabayashi
Fluoropyrimidine is commonly used to treat unresectable cases of metastatic colorectal cancer or as an adjuvant therapy for colorectal cancer. Dihydropyrimidine dehydrogenase (DPD) is an enzyme encoded by the DPYD gene, which is responsible for the rate-limiting step in pyrimidine catabolism and breaks down >80% of standard doses of 5-fluorouracil (5-FU). Reductions in DPD activity increase the half-life of 5-FU, resulting in excess 5-FU accumulation and toxicity, which can lead to life-threatening side effects. There have been several published case reports about DPD deficiency in colorectal cancer patients from Western countries. However, case reports of DPD deficiency in Japanese colorectal cancer patients are rare because the measurement of DPD activity is not covered by the public medical insurance system in Japan, and DPD activity is not currently measured in daily clinical practice. Furthermore, there have not been any reports about anticancer drug therapy for Japanese patients with DPD deficiency. In this report, we describe a case in which a Japanese patient with colorectal cancer was diagnosed with DPD deficiency. The DPD deficiency arose as a severe adverse effect of mFOLFOX6/CapOX treatment for recurrent colorectal cancer, and the patient was subsequently treated with TAS-102, without experiencing any severe adverse effects. We report this case along with a review of the literature.