Skip to main content

Advertisement

Log in

A phase II study of induction chemotherapy with gemcitabine plus S-1 followed by chemoradiotherapy for locally advanced pancreatic cancer

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

Abstract

Purpose

The aim of this study was to investigate the feasibility and efficacy of induction chemotherapy with gemcitabine and S-1 followed by chemoradiotherapy for locally advanced pancreatic cancer.

Methods

Patients with locally advanced unresectable pancreatic cancer received four cycles of induction chemotherapy consisting of 30-min intravenous infusions of gemcitabine 1,000 mg/m2 on days 1 and 8 and oral S-1 40 mg/m2 twice daily on days 1–14 of a 21-day cycle. Those without disease progression received chemoradiotherapy of 30 Gy in ten fractions with 250 mg/m2 of gemcitabine on days 1 and 8.

Results

A total of 20 patients were treated. Median follow-up time was 431 days (range 133–1,014 days). Four cycles of induction chemotherapy were completed in 18 patients, and 16 patients received chemoradiotherapy, which was completed without delay in all. Grade 3–4 toxicities associated with induction chemotherapy were neutropenia (50%); anemia (20%); thrombocytopenia (10%); febrile neutropenia (5%); nausea (10%); anorexia (10%); and vomiting, fatigue, dehydration, stomatitis, and rash (5%). Grade 3–4 toxicities among those receiving chemoradiotherapy were neutropenia (13%) and anemia (6%). Median progression-free survival was 8.1 months. Median overall survival was 14.4 months, with a 1-year survival rate of 54.2%.

Conclusions

The regimen of induction chemotherapy with gemcitabine and S-1 followed by chemoradiotherapy used in the present study demonstrated promising activity in locally advanced pancreatic cancer. Further consideration of radiation schedule and duration of induction chemotherapy is required to enhance the efficacy of this strategy.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Matsuda T, Marugame T, Kamo K, Katanoda K, Ajiki W, Sobue T, Japan Cancer Surveillance Research Group (2008) Cancer incidence and incidence rates in Japan in 2002: based on data from 11 population-based cancer registries. Jpn J Clin Oncol 38:641–648

    Article  PubMed  Google Scholar 

  2. Moertel CG, Childs DS Jr, Reitemeier RJ, Colby MY Jr, Holbrook MA (1969) Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet 2:865–867

    Article  CAS  PubMed  Google Scholar 

  3. Moertel CG, Frytak S, Hahn RG, O’Connell MJ, Reitemeier RJ, Rubin J et al (1981) Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer 48:1705–1710

    Article  CAS  PubMed  Google Scholar 

  4. Gastrointestinal Tumor Study Group (1988) Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Natl Cancer Inst 80:751–755

    Article  Google Scholar 

  5. Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouché O et al (2008) Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol 19:1592–1599

    Article  CAS  PubMed  Google Scholar 

  6. Loehrer PJ, Powell ME, Cardenes HR, Wagner L, Brell JM, Ramanathan RK et al. (2008) A randomized phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer. J Clin Oncol ASCO Annual Meeting Proceedings 26, Abstract 4506

  7. Liu RC, Traverso LW (2005) Diagnostic laparoscopy improves staging of pancreatic cancer deemed locally unresectable by computed tomography. Surg Endosc 19:638–642

    Article  CAS  PubMed  Google Scholar 

  8. Shoup M, Winston C, Brennan MF, Bassman D, Conlon KC (2004) Is there a role for staging laparoscopy in patients with locally advanced, unresectable pancreatic adenocarcinoma? J Gastrointest Surg 8:1068–1071

    Article  PubMed  Google Scholar 

  9. Jimenez RE, Warshaw AL, Fernandez-Del Castillo C (2000) Laparoscopy and peritoneal cytology in the staging of pancreatic cancer. J Hepatobiliary Pancreat Surg 7:15–20

    Article  CAS  PubMed  Google Scholar 

  10. Boku N, Yamamoto S, Shirao K, Doi T, Sawaki A, Koizumi W et al. (2007) Randomized phase III study of 5-fluorouracil (5-FU) alone versus combination of irinotecan and cisplatin (CP) versus S-1 alone in advanced gastric cancer (JCOG9912). J Clin Oncol ASCO Annual Meeting Proceedings, Part I. 25(18S), LBA4513

  11. Narahara H, Koizumi W, Hara T, Takagane A, Akiya T, Takagi M et al. (2007) Randomized phase III study of S-1 alone versus S-1 + cisplatin in the treatment for advanced gastric cancer (The SPIRITS trial) SPIRITS: S-1 plus cisplatin vs S-1 in RCT in the treatment for stomach cancer. J Clin Oncol ASCO Annual Meeting Proceedings, Part I; 25(18S), pp 4514

    Google Scholar 

  12. Okusaka T, Funakoshi A, Furuse J, Boku N, Yamao K, Ohkawa S, Saito H (2008) A late phase II study of S-1 for metastatic pancreatic cancer. Cancer Chemother Pharmacol 61:615–621

    Article  CAS  PubMed  Google Scholar 

  13. Nakamura K, Yamaguchi T, Ishihara T, Sudo K, Kato H, Saisho H (2006) Phase II trial of oral S-1 combined with gemcitabine in metastatic pancreatic cancer. Br J Cancer 94:1575–1579

    CAS  PubMed  Google Scholar 

  14. Ueno H, Okusaka T, Furuse J, Yamao K, Funakoshi A, Boku N et al. (2007) A multicenter phase II study of gemcitabine and S-1 combination therapy (GS therapy) in patients with metastatic pancreatic cancer. J Clin Oncol ASCO Annual Meeting Proceedings Part I, 25(18S), pp 4550

    Google Scholar 

  15. Ueno H, Okusaka T, Ikeda M, Ishiguro Y, Morizane C, Matsubara J et al (2005) A phase I study of combination chemotherapy with gemcitabine and oral S-1 for advanced pancreatic cancer. Oncology 69:421–427

    Article  CAS  PubMed  Google Scholar 

  16. Ikeda M, Okada S, Tokuuye K, Ueno H, Okusaka T (2002) A phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer. Br J Cancer 86:1551–1554

    Article  CAS  PubMed  Google Scholar 

  17. Blackstock AW, Bernard SA, Richards F, Eagle KS, Case LD, Poole ME et al (1999) Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer. J Clin Oncol 17:2208–2212

    CAS  PubMed  Google Scholar 

  18. Furuse J, Ishii H, Kawashima M, Nagase M, Nihei K, Nakachi K et al (2007) A phase I study of hypofractionated radiotherapy followed by systemic chemotherapy with full-dose gemcitabine in patients with unresectable locally advanced pancreatic cancer. Hepatogastroenterology 54:1575–1578

    PubMed  Google Scholar 

  19. Wolff RA, Evans DB, Gravel DM, Lenzi R, Pisters PW, Lee JE et al (2001) Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma. Clin Cancer Res 7:2246–2253

    CAS  PubMed  Google Scholar 

  20. Mishra G, Butler J, Ho C, Melin S, Case LD, Ennever PR et al (2005) Phase II trial of induction gemcitabine/CPT-11 followed by a twice-weekly infusion of gemcitabine and concurrent external beam radiation for the treatment of locally advanced pancreatic cancer. Am J Clin Oncol 28:345–350

    Article  CAS  PubMed  Google Scholar 

  21. Ko AH, Quivey JM, Venook AP, Bergsland EK, Dito E, Schillinger B et al (2007) A phase II study of fixed-dose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 68:809–816

    CAS  PubMed  Google Scholar 

  22. Moureau-Zabotto L, Phélip JM, Afchain P, Mineur L, André T, Vendrely V et al (2008) Concomitant administration of weekly oxaliplatin, fluorouracil continuous infusion, and radiotherapy after 2 months of gemcitabine and oxaliplatin induction in patients with locally advanced pancreatic cancer: a Groupe Coordinateur Multidisciplinaire en Oncologie phase II study. J Clin Oncol 26:1080–1085

    Article  CAS  PubMed  Google Scholar 

  23. Kurt E, Kurt M, Kanat O, Cetintas SK, Aygun S, Palazoglu T et al (2006) Phase II study of induction chemotherapy with gemcitabine plus 5-fluorouracil followed by gemcitabine-based concurrent chemoradiotherapy for unresectable locally advanced pancreatic cancer. Tumori 92:481–486

    CAS  PubMed  Google Scholar 

  24. Goldstein D, Van Hazel G, Walpole E, Underhill C, Kotasek D, Michael M et al (2007) Gemcitabine with a specific conformal 3D 5FU radiochemotherapy technique is safe and effective in the definitive management of locally advanced pancreatic cancer. Br J Cancer 97:464–471

    Article  CAS  PubMed  Google Scholar 

  25. Huguet F, André T, Hammel P, Artru P, Balosso J, Selle F et al (2007) Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol 25:326–331

    Article  CAS  PubMed  Google Scholar 

  26. Krishnan S, Rana V, Janjan NA, Varadhachary GR, Abbruzzese JL, Das P et al (2007) Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy. Cancer 110:47–55

    Article  PubMed  Google Scholar 

  27. Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schönekäs H, Rost A et al (2006) Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol 24:3946–3952

    Article  CAS  PubMed  Google Scholar 

  28. Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, GERCOR; GISCAD et al (2005) Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 23:3509–3516

    Article  CAS  PubMed  Google Scholar 

  29. Murphy JD, Adusumilli S, Griffith KA, Ray ME, Zalupski MM, Lawrence TS et al (2007) Full-dose gemcitabine and concurrent radiotherapy for unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 68:801–808

    CAS  PubMed  Google Scholar 

  30. Small W Jr, Berlin J, Freedman GM, Lawrence T, Talamonti MS, Mulcahy MF et al (2008) Full-dose gemcitabine with concurrent radiation therapy in patients with nonmetastatic pancreatic cancer: a multicenter phase II trial. J Clin Oncol 26:942–947

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank our patients and their families for their participation in this study. We appreciate our secretary, Ms Kayo Takei, for her devotion to the study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kohei Nakachi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nakachi, K., Furuse, J., Kinoshita, T. et al. 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 (2010). https://doi.org/10.1007/s00280-009-1193-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-009-1193-4

Keywords

Navigation