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01.04.2013 | Original Article

Phase I and pharmacokinetic study of gefitinib and S-1 combination therapy for advanced adenocarcinoma of the lung

verfasst von: Hidemi Kiyota, Isamu Okamoto, Masayuki Takeda, Haruko Daga, Tateaki Naito, Masaki Miyazaki, Hideaki Okada, Hidetoshi Hayashi, Kaoru Tanaka, Masaaki Terashima, Koichi Azuma, Haruyasu Murakami, Koji Takeda, Nobuyuki Yamamoto, Kazuhiko Nakagawa

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2013

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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/m² (level 1) and escalating to 80 mg/m² (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.

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Titel: Phase I and pharmacokinetic study of gefitinib and S-1 combination therapy for advanced adenocarcinoma of the lung
verfasst von: Hidemi Kiyota
Isamu Okamoto
Masayuki Takeda
Haruko Daga
Tateaki Naito
Masaki Miyazaki
Hideaki Okada
Hidetoshi Hayashi
Kaoru Tanaka
Masaaki Terashima
Koichi Azuma
Haruyasu Murakami
Koji Takeda
Nobuyuki Yamamoto
Kazuhiko Nakagawa
Publikationsdatum: 01.04.2013
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2013
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-013-2077-1

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Phase I and pharmacokinetic study of gefitinib and S-1 combination therapy for advanced adenocarcinoma of the lung