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

doi:10.1007/s00280-014-2563-0

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

The University of Tokyo

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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.

Original language	English
Pages (from-to)	911-915
Number of pages	5
Journal	Cancer Chemotherapy and Pharmacology
Volume	74
Issue number	5
DOIs	https://doi.org/10.1007/s00280-014-2563-0
Publication status	Published - Nov 2014
Externally published	Yes

Keywords

Chemotherapy
Gemcitabine
Leucovorin
Pancreatic cancer
S-1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00280-014-2563-0

Cite this

Nakai, Y., Isayama, H., Saito, K., Sasaki, T., Takahara, N., Hamada, T., Mizuno, S., Miyabayashi, K., Yamamoto, K., Mohri, D., Kogure, H., Yamamoto, N., Hirano, K., Ijichi, H., Tateishi, K., Tada, M., & Koike, K. (2014). A phase I trial of gemcitabine, S-1 and LV combination (GSL) therapy in advanced pancreatic cancer. Cancer Chemotherapy and Pharmacology, 74(5), 911-915. https://doi.org/10.1007/s00280-014-2563-0

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

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.",

keywords = "Chemotherapy, Gemcitabine, Leucovorin, Pancreatic cancer, S-1",

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

note = "Publisher Copyright: {\textcopyright} Springer-Verlag 2014.",

year = "2014",

month = nov,

doi = "10.1007/s00280-014-2563-0",

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Nakai, Y, Isayama, H, Saito, K, Sasaki, T, Takahara, N, Hamada, T, Mizuno, S, Miyabayashi, K, Yamamoto, K, Mohri, D, Kogure, H, Yamamoto, N, Hirano, K, Ijichi, H, Tateishi, K, Tada, M & Koike, K 2014, 'A phase I trial of gemcitabine, S-1 and LV combination (GSL) therapy in advanced pancreatic cancer', Cancer Chemotherapy and Pharmacology, vol. 74, no. 5, pp. 911-915. https://doi.org/10.1007/s00280-014-2563-0

TY - JOUR

T1 - A phase I trial of gemcitabine, S-1 and LV combination (GSL) therapy in advanced pancreatic cancer

AU - Nakai, Yousuke

AU - Isayama, Hiroyuki

AU - Saito, Kei

AU - Sasaki, Takashi

AU - Takahara, Naminatsu

AU - Hamada, Tsuyoshi

AU - Mizuno, Suguru

AU - Miyabayashi, Koji

AU - Yamamoto, Keisuke

AU - Mohri, Dai

AU - Kogure, Hirofumi

AU - Yamamoto, Natsuyo

AU - Hirano, Kenji

AU - Ijichi, Hideaki

AU - Tateishi, Keisuke

AU - Tada, Minoru

AU - Koike, Kazuhiko

PY - 2014/11

Y1 - 2014/11

N2 - 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.

AB - 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.

KW - Chemotherapy

KW - Gemcitabine

KW - Leucovorin

KW - Pancreatic cancer

KW - S-1

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U2 - 10.1007/s00280-014-2563-0

DO - 10.1007/s00280-014-2563-0

M3 - Article

C2 - 25143299

AN - SCOPUS:84919730381

SN - 0344-5704

VL - 74

SP - 911

EP - 915

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

IS - 5

ER -

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

Abstract

Keywords

UN SDGs

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