Safety and pharmacokinetics of S-1 in a recurrent colon cancer patient with chronic myeloid leukemia treated with dasatinib: a case report.
OBJECTIVE
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.


METHODS
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.
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Toshinori
T
Sueda
Toshihiro
T
Kudo
Daisuke
D
Sakai
Mamoru
M
Uemura
Junichi
J
Nishimura
Taishi
T
Hata
Ichiro
I
Takemasa
Tsunekazu
T
Mizushima
Hirofumi
H
Yamamoto
Sachiko
S
Ezoe
Kana
K
Matsumoto
Yuichiro
Y
Doki
Masaki
M
Mori
Taroh
T
Satoh
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069439:Dasatinib; D004338:Drug Combinations; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D010094:Oxonic Acid / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D005641:Tegafur / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000069439:Dasatinib