Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 4/2017

01-04-2017 | Original Article

A phase 1 study of gemcitabine/nab-paclitaxel/S-1 (GAS) combination neoadjuvant chemotherapy for patients with locally advanced pancreatic adenocarcinoma

Authors: Naru Kondo, Yoshiaki Murakami, Kenichiro Uemura, Takeshi Sudo, Yasushi Hashimoto, Naoya Nakagawa, Shinya Takahashi, Hiroki Ohge, Taijiro Sueda

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2017

Login to get access

Abstract

Purpose

To determine a recommended dose for a biweekly combination neoadjuvant chemotherapy including gemcitabine, nab-paclitaxel, and S-1 (GAS) for patients with locally advanced pancreatic ductal adenocarcinoma (LAPC).

Methods

Patients with borderline resectable or unresectable LAPC without distant metastasis were eligible for this study. The planned dosages of gemcitabine (mg/m2, day 1), nab-paclitaxel (mg/m2, day 1), and S-1 (mg/day, days 1–7) were 800/100/60–100 at level 1, and 1000/125/60–100 at level 2. The treatment cycle was repeated every 2 weeks, and patients were assessed for resectability and response to the treatment after 6 cycles. This study was registered with UMIN Clinical Trial Registry (UMIN000016630).

Results

We enrolled 16 patients with LAPC in this study. At dose level 1, one of 8 patients experienced dose-limiting toxicity (DLT). One of the next 8 patients also experienced DLT at dose level 2. Based on these results, level 2 was considered the recommended dose for this regimen. Pancreatectomy with curative intent could be performed in 13 of the 16 patients. R0 resection was performed in 12 of 13 patients.

Conclusion

In conclusion, recommended doses for a biweekly GAS chemotherapy regimen were determined as nab-paclitaxel: 125 mg/m2, gemcitabine: 1000 mg/m2 on day 1, S-1: <1.25 m2, 60 mg; 1.25–1.5 m2, 80 mg; >1.5 m2, 100 mg twice a day on days 1–7. GAS chemotherapy showed good preliminary efficacy with mild toxicity in this study, and warrants a further phase 2 trial to investigate the efficacy of the GAS regimen for LAPC.
Literature
1.
2.
3.
Li D, Xie K, Wolff R, Abbruzzese JL (2004) Pancreatic cancer. The Lancet 363:1049–1057CrossRef
4.
5.
Oettle H, Post S, Neuhaus P et al (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. Jama 297:267–277CrossRefPubMed
6.
Uesaka K, Boku N, Fukutomi A et al (2016) Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). The Lancet 388:248–257CrossRef
7.
Matsuno S, Egawa S, Fukuyama S et al (2004) Pancreatic Cancer Registry in Japan: 20 years of experience. Pancreas 28:219–230CrossRefPubMed
8.
Stathis A, Moore MJ (2010) Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev Clin Oncol 7:163–172CrossRefPubMed
9.
Sherman WH, Chu K, Chabot J et al (2015) Neoadjuvant gemcitabine, docetaxel, and capecitabine followed by gemcitabine and capecitabine/radiation therapy and surgery in locally advanced, unresectable pancreatic adenocarcinoma. Cancer 121:673–680CrossRefPubMed
10.
Sahora K, Kuehrer I, Eisenhut A et al (2011) NeoGemOx: Gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer. Surgery 149:311–320CrossRefPubMed
11.
Motoi F, Ishida K, Fujishima F et al (2013) Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: results from a prospective multi-institutional phase 2 trial. Ann Surg Oncol 20:3794–3801CrossRefPubMed
12.
Reni M, Cereda S, Balzano G et al (2009) Outcome of upfront combination chemotherapy followed by chemoradiation for locally advanced pancreatic adenocarcinoma. Cancer Chemother Pharmacol 64:1253–1259CrossRefPubMed
13.
Murakami Y, Uemura K, Sudo T et al (2016) Survival impact of neoadjuvant gemcitabine plus S-1 chemotherapy for patients with borderline resectable pancreatic carcinoma with arterial contact. Cancer Chemother Pharmacol 79(1):37–47
14.
Von Hoff DD, Ervin T, Arena FP et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369:1691–1703CrossRef
15.
Ueno H, Ioka T, Ikeda M et al (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 31:1640–1648CrossRefPubMed
16.
Yanagimoto H, Ishii H, Nakai Y et al (2014) Improved survival with combined gemcitabine and S-1 for locally advanced pancreatic cancer: pooled analysis of three randomized studies. J Hepatobiliary Pancreat Sci 21:761–766CrossRefPubMed
17.
18.
Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216CrossRef
19.
Padhani AR, Ollivier L (2001) The RECIST (response evaluation criteria in solid tumors) criteria: implications for diagnostic radiologists. Br J Radiol 74:983–986CrossRefPubMed
20.
James D., Brierley MKG, Christian Wittekind (2009) TNM Classification of Malignant Tumours, 7th Edition. Wiley-Blackwell, New York
21.
Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17:1471–1474CrossRefPubMed
22.
Hirano S, Kondo S, Hara T et al (2007) Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic body cancer: long-term results. Ann Surg 246:46–51CrossRefPubMedPubMedCentral
23.
Evans DB, Rich TA, Byrd DR et al (1992) Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg 127:1335–1339CrossRefPubMed
24.
Ueno H, Ikeda M, Ueno M et al (2016) Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. Cancer Chemother Pharmacol 77:595–603CrossRefPubMed
25.
Suker M, Beumer BR, Sadot E et al (2016) FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol 17:801–810CrossRefPubMed
26.
Allendorf JD, Lauerman M, Bill A et al (2008) Neoadjuvant chemotherapy and radiation for patients with locally unresectable pancreatic adenocarcinoma: feasibility, efficacy, and survival. J Gastrointest Surg 12:91–100CrossRefPubMed
27.
Golcher H, Brunner T, Grabenbauer G et al (2008) Preoperative chemoradiation in adenocarcinoma of the pancreas. A single centre experience advocating a new treatment strategy. Eur J Surg Oncol 34:756–764CrossRefPubMed
28.
Wilkowski R, Thoma M, Bruns C et al (2006) Chemoradiotherapy with gemcitabine and continuous 5-FU in patients with primary inoperable pancreatic cancer. JOP 7:349–360PubMed
29.
Conroy T, Desseigne F, Ychou M et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825CrossRefPubMed
30.
Petrelli F, Coinu A, Borgonovo K et al (2015) FOLFIRINOX-based neoadjuvant therapy in borderline resectable or unresectable pancreatic cancer: a meta-analytical review of published studies. Pancreas 44:515–521CrossRefPubMed
Metadata
Title
A phase 1 study of gemcitabine/nab-paclitaxel/S-1 (GAS) combination neoadjuvant chemotherapy for patients with locally advanced pancreatic adenocarcinoma
Authors
Naru Kondo
Yoshiaki Murakami
Kenichiro Uemura
Takeshi Sudo
Yasushi Hashimoto
Naoya Nakagawa
Shinya Takahashi
Hiroki Ohge
Taijiro Sueda
Publication date
01-04-2017
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2017
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-017-3274-0

Other articles of this Issue 4/2017

Cancer Chemotherapy and Pharmacology 4/2017 Go to the issue

Original Article

Correlation between clinical response to sorafenib in hepatocellular carcinoma treatment and polymorphisms of P-glycoprotein (ABCB1) and of breast cancer resistance protein (ABCG2): monocentric study

Original Article

An apparent clinical pharmacokinetic drug–drug interaction between bevacizumab and the anti-placental growth factor monoclonal antibody RO5323441 via a target-trapping mechanism

Original Article

XPG genetic polymorphisms and clinical outcome of patients with advanced non-small cell lung cancer under platinum-based treatment: a meta-analysis of 12 studies

Review Article

Polymeric micelles as mighty nanocarriers for cancer gene therapy: a review

Letter to the Editor

Reply: Methotrexate neurotoxicity due to drug interactions: an inadequate folinic acid effect

Original Article

Synthesis of short retinoidal amides related to fenretinide: antioxidant activities and differentiation-inducing ability
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits