Pharmacokinetic Study of Weekly (Days 1-5) Low-dose S-1 in Patients with Non-Small-Cell Lung Cancer

Author(s): Tsuyoshi Shoji, Makoto Sonobe, Hiroaki Sakai, Takuji Fujinaga, Toshihiko Sato, Fengshi Chen, Ryo Miyahara, Toru Bando, Hiromi Wada, Hiroshi Date.

Journal Name: Reviews on Recent Clinical Trials

Volume 7 , Issue 2 , 2012

Abstract:

Background: S-1, an oral fluoropyrimidine, is usually given for 4 weeks (80 mg/m2/day) followed by a 2-week rest. However, compliance with this regimen is unsatisfactory because of adverse events such as leukopenia, anorexia, and nausea. To reduce adverse effects and improve compliance, we studied a “5-day on/2-day off” low-dose regimen of S-1 and evaluated pharmacokinetics in patients with non-small-cell lung cancer (NSCLC).

Methods: Twelve patients with NSCLC were divided into 2 groups and received S-1 in a dose of 25 mg twice daily (level 1, n = 6) or 40 mg twice daily (level 2, n = 6) for 5 consecutive days followed by a 2-day rest (5 days on/2 days off) every week. Plasma 5-fluorouracil (5-FU) concentrations were measured.

Results: The maximum concentration in plasma and the area under the plasma concentration-time curve from 0 to 9 h were respectively 55.3 ± 21.1 ng/ml and 290.2 ± 95.7 ng·hr/ml for level 1, as compared with 104.2 ± 33.5 ng/ml and 541.9 ± 232.3 ng·hr/ml for level 2. These values were similar to those previously reported for a continuous intravenous infusion of 5-FU. Adverse events were grade 1 fatigue (n = 1 in each group) and anorexia (n = 1 in each group).

Conclusions: A “5-day on/2-day off” low-dose (40 mg twice daily) regimen of S-1 is feasible for the treatment of NSCLC, with acceptable plasma 5-FU concentrations and minimal adverse effects. A phase II or III trial of this regimen in an adjuvant setting is warranted in patients with NSCLC.

Keywords: Chemotherapy, low-dose administration, non-small-cell lung cancer, oral anticancer fluoropyrimidine agent, pharmacokinetic study, S-1

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Article Details

VOLUME: 7
ISSUE: 2
Year: 2012
Page: [167 - 172]
Pages: 6
DOI: 10.2174/157488712800100260
Price: $58

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