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

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

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)911-915
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Issue number5
Publication statusPublished - Nov 2014
Externally publishedYes


  • Chemotherapy
  • Gemcitabine
  • Leucovorin
  • Pancreatic cancer
  • S-1


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