title: Phase I and pharmacokinetic study of gefitinib and S-1 combination therapy for advanced adenocarcinoma of the lung.
abstract: BACKGROUND
  A phase I dose-escalation study was performed to investigate the safety and pharmacokinetics of the combination of S-1 and gefitinib in patients with pulmonary adenocarcinoma who had failed previous chemotherapy.
  
  
  METHODS
  Patients received gefitinib at a fixed daily oral dose of 250 mg, and S-1 was administered on days 1-14 every 21 days at doses starting at 60 mg/m(2) (level 1) and escalating to 80 mg/m(2) (level 2). The primary end point of the study was determination of the recommended dose for S-1 given in combination with a fixed dose of gefitinib.
  
  
  RESULTS
  Twenty patients were enrolled in the study. Two of the first six patients at dose level 2 experienced a dose-limiting toxicity (elevation of alkaline phosphatase of grade 3 in one patient; elevations of aspartate and alanine aminotransferases of grade 3 in the other). The recommended dose was thus determined as level 2, and an additional 11 patients were assigned to this level. All observed adverse events were well managed. The response rate was 50 % (10 of 20 patients), and the median progression-free survival (PFS) and overall survival times were 10.5 and 21.2 months, respectively. In EGFR mutation-positive patients (n = 9), seven patients achieved an objective response and the median PFS was 12.4 months, whereas none with wild-type EGFR (n = 6) responded. No pharmacokinetic interaction between S-1 and gefitinib was detected.
  
  
  CONCLUSIONS
  The combination of S-1 and gefitinib is well tolerated and appears to possess activity against EGFR mutation-positive NSCLC.
authors: Department of Medical Oncology, Faculty of Medicine, Kinki University, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan.
authors: Hidemi
authors: H
authors: Kiyota
authors: Isamu
authors: I
authors: Okamoto
authors: Masayuki
authors: M
authors: Takeda
authors: Haruko
authors: H
authors: Daga
authors: Tateaki
authors: T
authors: Naito
authors: Masaki
authors: M
authors: Miyazaki
authors: Hideaki
authors: H
authors: Okada
authors: Hidetoshi
authors: H
authors: Hayashi
authors: Kaoru
authors: K
authors: Tanaka
authors: Masaaki
authors: M
authors: Terashima
authors: Koichi
authors: K
authors: Azuma
authors: Haruyasu
authors: H
authors: Murakami
authors: Koji
authors: K
authors: Takeda
authors: Nobuyuki
authors: N
authors: Yamamoto
authors: Kazuhiko
authors: K
authors: Nakagawa
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D004338:Drug Combinations; D011799:Quinazolines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077156:Gefitinib