Skip to main content

Advertisement

SpringerLink
Log in

S-1 (Teysuno) and gemcitabine in Caucasian patients with unresectable pancreatic adenocarcinoma

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Gemcitabine has been standard of care in advanced pancreatic adenocarcinomas (PC) for almost two decades. Randomized, primarily Japanese, studies have shown promising efficacy when combined with S-1 (GemS-1); however, no data are published in Caucasian patients. We report the first study with a combination of GemS-1 in an unselected cohort of Caucasian PC patients.

Methods

In this observational cohort study, we analyzed efficacy and toxicity prospectively.

Results

From July 2012 to July 2014, 64 patients received at least one cycle of GemS-1. 16 patients started therapy with gemcitabine and capecitabine (GemCap) but switched to GemS-1 after median 3 cycles of GemCap due to toxicity (hand-foot syndrome). 48 patients received GemS-1 as initial therapy. For the complete cohort, median age was 68 years (range 44–80); 22 patients (34%) had locally advanced PC; 42 patients (66%) had metastatic disease. Five patients had received prior adjuvant therapy with gemcitabine and 9 pts had received prior first-line therapy. The most common adverse event was fatigue (86%), however, only grade 3 in 3%. Five patients (8%) developed febrile neutropenia. Median PFS was 8.1 (95% CI 6.9–9.0) months and median OS was 11.7 (95% CI 10.7–13.1) months in the whole GemS-1 population. In the 48 patients starting with GemS-1, median PFS was 7.7 (95% CI 6.7–8.9) months and median OS was 11.5 (95% CI 9.7–12.3) months.

Conclusions

The combination of gemcitabine and S-1 is safe and associated with promising efficacy in a Caucasian population; however, this needs to be confirmed in prospective clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D, Bray F (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49(6):1374–1403. https://doi.org/10.1016/j.ejca.2012.12.027

    Article  CAS  PubMed  Google Scholar 

  2. Bjerregaard JK, Mortensen MB, Pfeiffer P (2016) Trends in cancer of the liver, gall bladder, bile duct, and pancreas in elderly in Denmark, 1980–2012. Acta Oncol 55 (Suppl 1):40–45. https://doi.org/10.3109/0284186x.2015.1114675

    Article  PubMed  Google Scholar 

  3. Bjerregaard JK, Mortensen MB, Schonnemann KR, Pfeiffer P (2013) Characteristics, therapy and outcome in an unselected and prospectively registered cohort of pancreatic cancer patients. Eur J Cancer 49(1):98–105. https://doi.org/10.1016/j.ejca.2012.07.017

    Article  CAS  PubMed  Google Scholar 

  4. Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15(6):2403–2413. https://doi.org/10.1200/jco.1997.15.6.2403

    Article  CAS  PubMed  Google Scholar 

  5. Heinemann V, Boeck S, Hinke A, Labianca R, Louvet C (2008) Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer. BMC Cancer 8:82. https://doi.org/10.1186/1471-2407-8-82

    Article  PubMed  PubMed Central  Google Scholar 

  6. 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(18):1691–1703. https://doi.org/10.1056/NEJMoa1304369

    Article  Google Scholar 

  7. 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 (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364(19):1817–1825. https://doi.org/10.1056/NEJMoa1011923

    Article  CAS  PubMed  Google Scholar 

  8. Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S (2010) Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol 28(9):1547–1553. https://doi.org/10.1200/jco.2009.25.4706

    Article  CAS  PubMed  Google Scholar 

  9. Sanford M (2013) S-1 (Teysuno(R)): a review of its use in advanced gastric cancer in non-Asian populations. Drugs 73(8):845–855. https://doi.org/10.1007/s40265-013-0062-y

    Article  CAS  PubMed  Google Scholar 

  10. 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):1197–1204. https://doi.org/10.1007/s00280-012-1822-1

    Article  CAS  PubMed  Google Scholar 

  11. 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):1934–1939. https://doi.org/10.1038/bjc.2012.183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 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):1640–1648. https://doi.org/10.1200/jco.2012.43.3680

    Article  CAS  PubMed  Google Scholar 

  13. Sudo K, Ishihara T, Hirata N, Ozawa F, Ohshima T, Azemoto R, Shimura K, Nihei T, Nishino T, Nakagawa A, Nakamura K, Hara T, Tada M, Mikata R, Tawada K, Yokosuka O, Nakaji S, Yamaguchi T (2014) Randomized controlled study of gemcitabine plus S-1 combination chemotherapy versus gemcitabine for unresectable pancreatic cancer. Cancer Chemother Pharmacol 73(2):389–396. https://doi.org/10.1007/s00280-013-2368-6

    Article  CAS  PubMed  Google Scholar 

  14. Liu Y, Huang QK, Hong WD, Wu JM, Sun XC (2015) The addition of S-1 to gemcitabine-based chemotherapy improves survival with increased toxicity for patients with advanced pancreatic cancer: combined meta-analysis of efficacy and safety profile. Clin Res Hepatol Gastroenterol 39(2):254–260. https://doi.org/10.1016/j.clinre.2014.08.012

    Article  CAS  PubMed  Google Scholar 

  15. Winther SB, Zubcevic K, Qvortrup C, Vestermark LW, Jensen HA, Krogh M, Sorbye H, Pfeiffer P (2016) Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): findings from an observational chart review. Acta Oncol. https://doi.org/10.3109/0284186x.2016.1161825

    Google Scholar 

  16. Kwakman JJ, Baars A, Boot H, Pruijt JF, Winther SB, Pfeiffer P, Punt CJ (2017) Tolerability of the oral fluoropyrimidine S-1 after hand-foot syndrome-related discontinuation of capecitabine in western cancer patients. Acta Oncol. https://doi.org/10.1080/0284186x.2016.1278459

    Google Scholar 

  17. Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP (2009) Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 27(33):5513–5518. https://doi.org/10.1200/jco.2009.24.2446

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Stine Braendegaard Winther and Jon Kroll Bjerregaard shared first authorship.

Authors and Affiliations

  1. Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark

    Stine Braendegaard Winther, Jon Kroll Bjerregaard, Katrine Rahbek Schonnemann, Mathilde Weisz Ejlsmark, Merete Krogh, Helle Anita Jensen & Per Pfeiffer

  2. Department of Clinical Research, University of Southern Denmark, Winsløwparken 19, 3. Sal, 5000, Odense C, Denmark

    Stine Braendegaard Winther & Per Pfeiffer

  3. Odense Pancreas Center (OPAC), Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark

    Per Pfeiffer

Authors
  1. Stine Braendegaard Winther
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jon Kroll Bjerregaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katrine Rahbek Schonnemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mathilde Weisz Ejlsmark
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Merete Krogh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Helle Anita Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Per Pfeiffer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stine Braendegaard Winther.

Ethics declarations

Conflict of interest

Per Pfeiffer: Symposia or lectures for Amgen, Bayer, Celgene, Merck-Serono, MSD, Nordic Drugs, Roche, Sanofi, Taiho. Stine Winther: Lectures for Nordic Drugs. Jon Kroll Bjerregaard: no conflict of interest. Katrine Rahbek Schonnemann: no conflict of interest. Mathilde Weisz Ejlsmark: no conflict of interest. Merete Krogh: no conflict of interest. Helle Anita Jensen: no conflict of interest.

Ethical approval

The registry setup is according to Danish Law for Clinical Research. It is approved by the Danish Data Protection Agency (j. no. 13/41743) and it complies with the 1964 Helsinki declaration and its later amendments.

Informed consent

For this type of study formal consent is not required.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Winther, S.B., Bjerregaard, J.K., Schonnemann, K.R. et al. S-1 (Teysuno) and gemcitabine in Caucasian patients with unresectable pancreatic adenocarcinoma. Cancer Chemother Pharmacol 81, 573–578 (2018). https://doi.org/10.1007/s00280-018-3528-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-018-3528-5

Keywords

Search

Navigation