title: Phase I study of docetaxel plus S-1 combination chemotherapy for recurrent non-small cell lung cancer.
abstract: S-1 is a novel oral fluorouracil prodrug that plays a role in non-small cell lung cancer (NSCLC). Docetaxel (DTX) is one of the standard agents for relapsed NSCLC. We performed a phase I study of DTX plus S-1 combination therapy as second-line treatment for NSCLC to determine the maximum tolerated dose (MTD) and recommended dose (RD). Patients with recurrent NSCLC, aged 20-74 years with an Eastern Cooperative Oncology Group performance status of 0-1 and measurable lesions, were enrolled. The treatment consisted of four dose levels. The patients received DTX (40-60 mg/m(2) intravenously on day 1) and S-1 (65-80 mg/m(2) orally, daily on days 1-14) for each 21-day cycle. Three to six patients were treated at each dose level with the two drugs, with MTD defined as the dose level at which dose-limiting toxicity (DLT) occurred in 33% of the patients. A total of 17 patients were enrolled. At dose level 4 (DTX, 60 mg/m(2); S-1, 80 mg/m(2)) 3 of 5 patients experienced DLT and this level was regarded as the MTD. Therefore, dose level 3 (DTX, 60 mg/m(2); S-1, 65 mg/m(2)) was selected as the RD for subsequent studies. The DLTs were neutropenia (grade 4) and mucositis (grade 3). The response rate was 5.9% (1 of 17 patients achieved a partial response) and 14 of 17 patients achieved stable disease. This combination regimen showed a tolerable and manageable profile in recurrent NSCLC and therefore warrants further evaluation.
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima 734-8551, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Fujitaka
authors.forename: Noboru
authors.initials: N
authors.lastname: Hattori
authors.forename: Tadashi
authors.initials: T
authors.lastname: Senoo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwamoto
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ohshimo
authors.forename: Masashi
authors.initials: M
authors.lastname: Kanehara
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Haruta
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murai
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno