A phase I trial of gemcitabine, S-1 and LV combination (GSL) therapy in advanced pancreatic cancer
详细信息 查看全文
- 作者：Yousuke Nakai (1)
Hiroyuki Isayama (1)
Kei Saito (1)
Takashi Sasaki (1)
Naminatsu Takahara (1)
Tsuyoshi Hamada (1)
Suguru Mizuno (1)
Koji Miyabayashi (1)
Keisuke Yamamoto (1)
Dai Mohri (1)
Hirofumi Kogure (1)
Natsuyo Yamamoto (1)
Kenji Hirano (1)
Hideaki Ijichi (1)
Keisuke Tateishi (1)
Minoru Tada (1)
Kazuhiko Koike (1) - 关键词：Pancreatic cancer ; Chemotherapy ; Gemcitabine ; S ; 1 ; Leucovorin
- 刊名：Cancer Chemotherapy and Pharmacology
- 出版年：2014
- 出版时间：November 2014
- 年：2014
- 卷：74
- 期：5
- 页码：911-915
- 全文大小：185 KB
- 参考文献：1. Nakai Y, Isayama H, Sasaki T, Sasahira N, Ito Y, Kogure H, Togawa O, Matsubara S, Arizumi T, Yagioka H, Yashima Y, Kawakubo K, Mizuno S, Yamamoto K, Hirano K, Tsujino T, Ijichi H, Tateishi K, Toda N, Tada M, Omata M, Koike K (2010) Impact of S-1 on the survival of patients with advanced pancreatic cancer. Pancreas 39(7):989-93. doi:10.1097/MPA.0b013e3181d91936 CrossRef
2. Nakai Y, Isayama H, Sasaki T, Sasahira N, Kogure H, Hirano K, Tsujino T, Ijichi H, Tateishi K, Tada M, Omata M, Koike K (2010) Impact of S-1 in patients with gemcitabine-refractory pancreatic cancer in Japan. Jpn J Clin Oncol 40(8):774-80. doi:10.1093/jjco/hyq059 CrossRef
3. Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M (2013) Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol 31(13):1640-648. doi:10.1200/jco.2012.43.3680 CrossRef
4. Uesaka K, Fukutomi A, Boku N, Kanemoto H, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Nakamura T, Kanai M, Hirano S, Yoshikawa Y, Ohashi Y (2013) Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer (JASPAC-01 study). ASCO Meeting Abstracts 31 (4_suppl):145
5. Ueno H, Okusaka T, Ikeda M, Ishiguro Y, Morizane C, Matsubara J, Furuse J, Ishii H, Nagase M, Nakachi K (2005) A phase I study of combination chemotherapy with gemcitabine and oral S-1 for advanced pancreatic cancer. Oncology 69(5):421-27. doi:10.1159/000089997 CrossRef
6. Ueno H, Okusaka T, Furuse J, Yamao K, Funakoshi A, Boku N, Ohkawa S, Yokosuka O, Tanaka K, Moriyasu F, Nakamori S, Sato T (2011) Multicenter phase II study of gemcitabine and S-1 combination therapy (GS Therapy) in patients with metastatic pancreatic cancer. Jpn J Clin Oncol 41(8):953-58. doi:10.1093/jjco/hyr090 CrossRef
7. Nakai Y, Isayama H, Sasaki T, Sasahira N, Tsujino T, Toda N, Kogure H, Matsubara S, Ito Y, Togawa O, Arizumi T, Hirano K, Tada M, Omata M, Koike K (2012) A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study. Br J Cancer 106(12):1934-939. doi:10.1038/bjc.2012.183 CrossRef
8. Ozaka M, Matsumura Y, Ishii H, Omuro Y, Itoi T, Mouri H, Hanada K, Kimura Y, Maetani I, Okabe Y, Tani M, Ikeda T, Hijioka S, Watanabe R, Ohoka S, Hirose Y, Suyama M, Egawa N, Sofuni A, Ikari T, Nakajima T (2012) Randomized phase II study of gemcitabine and S-1 combination versus gemcitabine alone in the treatment of unresectable advanced pancreatic cancer (Japan Clinical Cancer Research Organization PC-01 study). Cancer Chemother Pharmacol 69(5):1197-204. doi:10.1007/s00280-012-1822-1 CrossRef
9. Okusaka T, Ikari T, Isayama H, Furuse J, Ishii H, Nakai Y, Imai S, Okamura S, Hamada C (2013) Efficacy and safety of gemcitabine plus S-1 treatment in locally advanced and metastatic pancreatic cancer: A pooled analysis of three randomized trials using updated individual patient data. Eur J Cancer 49(Suppl 2):S618
10. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M, Groupe Tumeurs Digestives of U, Intergroup P (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. New Engl J Med 364(19):1817-825. doi:10.1056/NEJMoa1011923- 作者单位：Yousuke Nakai (1)
Hiroyuki Isayama (1)
Kei Saito (1)
Takashi Sasaki (1)
Naminatsu Takahara (1)
Tsuyoshi Hamada (1)
Suguru Mizuno (1)
Koji Miyabayashi (1)
Keisuke Yamamoto (1)
Dai Mohri (1)
Hirofumi Kogure (1)
Natsuyo Yamamoto (1)
Kenji Hirano (1)
Hideaki Ijichi (1)
Keisuke Tateishi (1)
Minoru Tada (1)
Kazuhiko Koike (1)
1. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan- ISSN：1432-0843
- 作者单位：Yousuke Nakai (1)
文摘
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-, every 2?weeks. A standard -?+?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 ?0?% 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.