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01.11.2014 | Original Article

A phase I trial of gemcitabine, S-1 and LV combination (GSL) therapy in advanced pancreatic cancer

verfasst von: Yousuke Nakai, Hiroyuki Isayama, Kei Saito, Takashi Sasaki, Naminatsu Takahara, Tsuyoshi Hamada, Suguru Mizuno, Koji Miyabayashi, Keisuke Yamamoto, Dai Mohri, Hirofumi Kogure, Natsuyo Yamamoto, Kenji Hirano, Hideaki Ijichi, Keisuke Tateishi, Minoru Tada, Kazuhiko Koike

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2014

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Abstract

Purpose

In our previous randomized controlled trial, the addition of S-1 to gemcitabine for advanced pancreatic cancer did not prolong overall survival (OS) significantly, despite its higher response rate and longer progression-free survival (PFS). Leucovorin is known to enhance efficacy of S-1, and we conducted this phase I trial of combination therapy of gemcitabine, S-1 and leucovorin (GSL).

Methods

Patients with advanced pancreatic cancer who had received no prior chemotherapy were eligible for this study. Gemcitabine was administered at an escalating dose of 600, 800 and 1,000 mg/m² over 30 min on day 1, and oral S-1 at a dose of 40 mg/m² twice daily and oral leucovorin at a dose of 25 mg twice daily on days 1–7, every 2 weeks. A standard “3 + 3” phase I dose escalation design was utilized.

Results

Fifteen patients were enrolled across three dose levels. Three patients developed DLTs: two patients in level 1 (grade 3 anorexia in 1 and grade 3 anorexia, stomatitis and diarrhea in 1) and one patient in level 2 (grade 3 deep vein thrombosis). No DLT was observed in level 3. Response rate and the disease control rate were 33 and 93 %, respectively. The median PFS and OS were 5.4 and 16.6 months. Ten of 12 patients (83 %) with elevated CA19-9 at baseline had a ≥50 % decline.

Conclusions

RD of gemcitabine in GSL was determined as 1,000 mg/m². GSL was well tolerable and showed promising results in advanced pancreatic cancer.

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Titel: A phase I trial of gemcitabine, S-1 and LV combination (GSL) therapy in advanced pancreatic cancer
verfasst von: Yousuke Nakai
Hiroyuki Isayama
Kei Saito
Takashi Sasaki
Naminatsu Takahara
Tsuyoshi Hamada
Suguru Mizuno
Koji Miyabayashi
Keisuke Yamamoto
Dai Mohri
Hirofumi Kogure
Natsuyo Yamamoto
Kenji Hirano
Hideaki Ijichi
Keisuke Tateishi
Minoru Tada
Kazuhiko Koike
Publikationsdatum: 01.11.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2014
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-014-2563-0

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A phase I trial of gemcitabine, S-1 and LV combination (GSL) therapy in advanced pancreatic cancer