Top

Published in:

01-01-2017 | Original Article

Survival impact of neoadjuvant gemcitabine plus S-1 chemotherapy for patients with borderline resectable pancreatic carcinoma with arterial contact

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

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2017

Abstract

Purpose

The aim of this study was to evaluate the efficacy of neoadjuvant gemcitabine plus S-1 (GS) chemotherapy as measured by overall survival for patients with pancreatic carcinoma with arterial contact.

Methods

Medical records of 77 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection were analyzed retrospectively. These patients were divided into two groups: patients who underwent upfront surgery and patients who underwent tumor resection after neoadjuvant GS chemotherapy. Clinicopathological factors were compared between the two groups.

Results

Of the 77 patients, 25 patients underwent upfront surgery while the remaining 52 patients received neoadjuvant GS chemotherapy. Seven patients did not undergo tumor resection due to distant metastasis. No serious adverse effects associated with neoadjuvant GS chemotherapy were observed. The R0 resection rate of patients who received neoadjuvant GS chemotherapy was significantly higher than that of patients who did not (P < 0.001). Overall survival of patients who received neoadjuvant GS chemotherapy was significantly longer than that of patients who did not among all 77 patients (P = 0.003, median survival time, 27.1 vs. 11.6 months) as well as among the 70 patients who underwent tumor resection (P = 0.001, median survival time, 27.2 vs. 11.6 months). Multivariate analysis demonstrated that neoadjuvant GS chemotherapy was an independent prognostic factor of overall survival for patients who underwent tumor resection (P = 0.019).

Conclusions

Neoadjuvant GS chemotherapy may provide a survival benefit to patients with pancreatic carcinoma with arterial contact.

National Comprehensive Cancer Network (2016) NCCN clinical practice guidelines in oncology. Pancreatic adenocarcinoma, version 2, 2016 edn. http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed 2 Oct 2016

Kato H, Usui M, Isaji S, Nagakawa T, Wada K, Unno M, Nakao A, Miyakawa S, Ohta T (2013) Clinical features and treatment outcome of borderline resectable pancreatic head/body cancer: a multi-institutional survey by the Japanese Society of Pancreatic Surgery. J Hepatobiliary Pancreat Sci 20:601–610. doi:10.1007/s00534-013-0595-1 CrossRefPubMed

Murakami Y, Satoi S, Sho M, Motoi F, Matsumoto I, Kawai M, Honda G, Uemura K, Yanagimoto H, Shinzeki M, Kurata M, Kinoshita S, Yamaue H, Unno M (2015) National comprehensive cancer network resectability status for pancreatic carcinoma predicts overall survival. World J Surg 39:2306–2314. doi:10.1007/s00268-015-3096-3 CrossRefPubMed

Nakachi K, Furuse J, Kinoshita T, Kawashima M, Ishii H, Ikeda M, Mitsunaga S, Shimizu S (2010) A phase II study of induction chemotherapy with gemcitabine plus S-1 followed by chemoradiotherapy for locally advanced pancreatic cancer. Cancer Chemother Pharmacol 66:527–534. doi:10.1007/s00280-009-1193-4 CrossRefPubMed

Shinchi H, Maemura K, Mataki Y, Kurahara H, Sakoda M, Ueno S, Hiraki Y, Nakajo M, Natsugoe S, Takao S (2012) A phase II study of oral S-1 with concurrent radiotherapy followed by chemotherapy with S-1 alone for locally advanced pancreatic cancer. J Hepatobiliary Pancreat Sci 19:152–158. doi:10.1007/s00534-011-0400-y CrossRefPubMed

Sudo K, Yamaguchi T, Ishihara T, Nakamura K, Hara T, Denda T, Tawada K, Imagumbai T, Araki H, Sakai M, Hatano K, Kawakami H, Uno T, Ito H, Yokosuka O (2012) Phase II study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 80:119–125. doi:10.1016/j.ijrobp.2010.01.027 CrossRef

Ishii H, Furuse J, Boku N, Okusaka T, Ikeda M, Ohkawa S, Fukutomi A, Hamamoto Y, Nakamura K, Fukuda H, JCOG Gastrointestinal Oncology Study Group (2010) Phase II study of gemcitabine chemotherapy alone for locally advanced pancreatic carcinoma: JCOG0506. Jpn J Clin Oncol 40:573–579. doi:10.1093/jjco/hyq011 CrossRefPubMed

Katz MH, Fleming JB, Bhosale P, Varadhachary G, Lee JE, Wolff R, Wang H, Abbruzzese J, Pisters PW, Vauthey JN, Charnsangavej C, Tamm E, Crane CH, Balachandran A (2012) Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer 118:5749–5756. doi:10.1002/cncr.27636 CrossRefPubMed

Tzeng CW, Balachandran A, Ahmad M, Lee JE, Krishnan S, Wang H, Crane CH, Wolff RA, Varadhachary GR, Pisters PW, Aloia TA, Vauthey JN, Fleming JB, Katz MH (2014) Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer. HPB (Oxford) 16:430–438. doi:10.1111/hpb.12154 CrossRef

10.

Sho M, Akahori T, Tanaka T, Kinoshita S, Nagai M, Tamamoto T, Ohbayashi C, Hasegawa M, Kichikawa K, Nakajima Y (2015) Importance of resectability status in neoadjuvant treatment for pancreatic cancer. J Hepatobiliary Pancreat Sci 22:563–570. doi:10.1002/jhbp.258 CrossRefPubMed

11.

Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, Sabbatino F, Santos DD, Allen JN, Blaszkowsky LS, Clark JW, Faris JE, Goyal L, Kwak EL, Murphy JE, Ting DT, Wo JY, Zhu AX, Warshaw AL, Lillemoe KD, Fernández-del Castillo C (2015) Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg 261:12–17. doi:10.1097/SLA.0000000000000867 CrossRefPubMedPubMedCentral

12.

Blazer M, Wu C, Goldberg RM, Phillips G, Schmidt C, Muscarella P, Wuthrick E, Williams TM, Reardon J, Ellison EC, Bloomston M, Bekaii-Saab T (2015) Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Ann Surg Oncol 22:1153–1159. doi:10.1245/s10434-014-4225-1 CrossRefPubMed

13.

Fujii T, Yamada S, Murotani K, Kanda M, Sugimoto H, Nakao A, Kodera Y (2015) Inverse probability of treatment weighting analysis of upfront surgery versus neoadjuvant chemoradiotherapy followed by surgery for pancreatic adenocarcinoma with arterial abutment. Medicine (Baltimore) 94:e1647. doi:10.1097/MD.0000000000001647 CrossRef

14.

Yanagimoto H, Ishii H, Nakai Y, Ozaka M, Ikari T, Koike K, Ueno H, Ioka T, Satoi S, Sho M, Okusaka T, Tanaka M, Shimokawa T, Kwon AH, Isayama H (2014) Improved survival with combined gemcitabine and S-1 for locally advanced pancreatic cancer: pooled analysis of three randomized studies. J Hepatobiliary Pancreat Sci 21:761–766. doi:10.1002/jhbp.130 CrossRefPubMed

15.

Hirano S, Kondo S, Hara T, Ambo Y, Tanaka E, Shichinohe T, Suzuki O, Hazama K (2007) Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic body cancer: long-term results. Ann Surg 246:46–51. doi:10.1097/01.sla.0000258608.52615.5a CrossRefPubMedPubMedCentral

16.

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 31:1640–1648. doi:10.1200/JCO.2012.43.3680 CrossRefPubMed

17.

Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Nakagawa N, Ohge H, Sueda T (2008) Adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma. Am J Surg 195:757–762. doi:10.1016/j.amjsurg.2007.04.018 CrossRefPubMed

18.

Murakami Y, Uemura K, Hashimoto Y, Kondo N, Nakagawa N, Takahashi S, Shintakuya R, Sueda T (2016) Survival effects of adjuvant gemcitabine plus S-1 chemotherapy on pancreatic carcinoma stratified by preoperative resectablity status. J Surg Oncol 113:405–412. doi:10.1002/jso.24156 CrossRefPubMed

19.

Sobin LH, Gospodarowicz MK, Wittekind C (eds) (2010) Internatinal Union Against Cancer (UICC): TNM classification of malignant tumours, 7th edn. Wiley-Blackwell, New York

20.

Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (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 92:205–216CrossRefPubMed

21.

Bassi C, Dervenis C, Butturini G, Fingerhut A, Yeo C, Izbicki J, Neoptolemos J, Sarr M, Traverso W, Buchler M, International Study Group on Pancreatic Fistula Definition (2005) Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 138:8–13. doi:10.1016/j.surg.2005.05.001 CrossRefPubMed

22.

Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications. A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213CrossRefPubMedPubMedCentral

23.

Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M, Groupe Tumeurs Digestives of Unicancer, PRODIGE Intergroup (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825. doi:10.1056/NEJMoa1011923 CrossRefPubMed

24.

Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369:1691–1703. doi:10.1056/NEJMoa1304369 CrossRef

Title: Survival impact of neoadjuvant gemcitabine plus S-1 chemotherapy for patients with borderline resectable pancreatic carcinoma with arterial contact
Authors: Yoshiaki Murakami
Kenichiro Uemura
Takeshi Sudo
Yasushi Hashimoto
Naru Kondo
Naoya Nakagawa
Shinya Takahashi
Taijiro Sueda
Publication date: 01-01-2017
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2017
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-016-3199-z

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

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2017

Clinical outcome of high-dose bolus intravenous interleukin-2 with a modified administration schedule for Asian patients with metastatic renal cell carcinoma

Phase I clinical and pharmacokinetic study of S-1 plus oral leucovorin in patients with metastatic colorectal cancer

Rituximab to treat gemcitabine-induced hemolytic–uremic syndrome (HUS) in pancreatic adenocarcinoma: a case series and literature review

Synergistic disruption of ERα/HER2 crosstalk by endoxifen and lapatinib in breast cancer cells

Etirinotecan pegol administration is associated with lower incidences of neutropenia compared to irinotecan administration

Long noncoding RNA GAS5 inhibits malignant proliferation and chemotherapy resistance to doxorubicin in bladder transitional cell carcinoma

Keynote webinar | Spotlight on antibody–drug conjugates in cancer