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Safety and pharmacokinetics of S-1 in a recurrent colon cancer patient with chronic myeloid leukemia treated with dasatinib: a case report
Authors:Toshinori Sueda  Toshihiro Kudo  Daisuke Sakai  Mamoru Uemura  Junichi Nishimura  Taishi Hata  Ichiro Takemasa  Tsunekazu Mizushima  Hirofumi Yamamoto  Sachiko Ezoe  Kana Matsumoto  Yuichiro Doki  Masaki Mori  Taroh Satoh
Institution:1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
2. Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, 2-2 YamadaOka, Suita, Osaka, 565-0871, Japan
3. Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan
4. Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Woman’s College of Liberal Arts, Kyoto, Japan
Abstract:

Purpose

The safety of S-1 in recurrent colorectal cancer patients with chronic myeloid leukemia (CML) treated with dasatinib has not been established. We evaluated the safety and pharmacokinetics of S-1 in a recurrent colon cancer patient with CML treated with dasatinib.

Patient

A 70-year-old man had undergone surgery three times for sigmoid colon cancer and recurrence. Systemic chemotherapy with S-1 plus oxaliplatin plus bevacizumab as a clinical trial had already been administered because of metastatic colon cancer. The patient’s medical history was CML, and he had been receiving dasatinib treatment (100 mg once daily). Based on the diagnosis of unresectable and multiple metastases, S-1 monotherapy was started. S-1 (120 mg/day) was taken for 28 consecutive days, followed by a 14-day rest. Blood samples were obtained before and after the first administration of S-1. The plasma pharmacokinetics of S-1 were comparable to a pharmacokinetics study of S-1.

Results

The area under the plasma concentration–time curve (AUC0–8) of tegafur (FT), 5-chloro-2, 4-dihydroxypyridine (CDHP), oxonate (Oxo), and 5-fluorouracil (5-FU) was 4,309.2, 716.3, 86.8, and 492.75 ng h/mL, respectively, after S-1 administration. The pharmacokinetics of FT, CDHP, Oxo, and 5-FU after treatment with S-1 were not significantly different from a phase I pharmacokinetics study of S-1. During treatment with S-1 and dasatinib, CML relapse and serious myelosuppression were not observed.

Conclusions

Our report suggests that S-1 is an important treatment option for recurrent colorectal cancer in patients with CML treated with dasatinib.
Keywords:
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