Phase I clinical and pharmacokinetic study of S-1 plus oral leucovorin in patients with metastatic colorectal cancer
| Autor: | Hiroyuki Narahara, Ichinosuke Hyodo, Tomohiro Nishina, Naotoshi Sugimoto, Takayuki Yoshino, Narikazu Boku, Kunihiro Yoshisue |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Oncology
Adult Male Cancer Research medicine.medical_specialty Colorectal cancer Leucovorin Administration Oral Toxicology Tegafur 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Oral administration Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Pharmacology (medical) 030212 general & internal medicine Adverse effect Stomatitis Aged Pharmacology business.industry Middle Aged medicine.disease digestive system diseases Confidence interval stomatognathic diseases Diarrhea Drug Combinations Oxonic Acid 030220 oncology & carcinogenesis Female medicine.symptom business Colorectal Neoplasms medicine.drug |
| Zdroj: | Cancer chemotherapy and pharmacology. 79(1) |
| ISSN: | 1432-0843 |
| Popis: | S-1 has shown a response rate of 35% in chemonaive patients with metastatic colorectal cancer (mCRC). Leucovorin enhances the antitumor activity of 5-fluorouracil, and concurrent oral administration of S-1 and leucovorin may represent a more active treatment option for mCRC. S-1 (35 mg/m2) and leucovorin (25 mg/body) were orally administered twice daily to chemonaive patients with mCRC. Predefined dose (schedule)-limiting toxicities (DLTs) during the first course and treatment continuity during the first two courses were evaluated during three periods of treatment with S-1 plus leucovorin (level 0, 2 weeks; level 1, 3 weeks; and level 2, 4 weeks), each followed by a 2-week rest. The pharmacokinetics (PK) of S-1 and leucovorin were studied on days 1 and 14 of the first course. Fifteen patients were enrolled. All three patients had DLTs at level 2, and this level was considered the maximum tolerated schedule. Level 0 was designated as the recommended schedule based on the incidences of DLTs and treatment continuity. The main toxic effects were gastrointestinal, such as diarrhea and stomatitis. There was no grade 4 adverse event or treatment-related death. The overall response rate was 67% (95% confidence interval, 38–88%). The PK profiles of S-1 plus leucovorin were similar to those in previous studies. The recommended schedule was 2 weeks of S-1 plus leucovorin followed by a 2-week rest. The increased response and gastrointestinal toxicities of S-1 plus leucovorin as compared with S-1 monotherapy suggest that co-administration of leucovorin enhanced the activity of S-1. |
| Databáze: | OpenAIRE |
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