Cancer Chemotherapy and Pharmacology

, Volume 66, Issue 3, pp 527–534 | Cite as

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

  • Kohei Nakachi
  • Junji Furuse
  • Taira Kinoshita
  • Mitsuhiko Kawashima
  • Hiroshi Ishii
  • Masafumi Ikeda
  • Shuichi Mitsunaga
  • Satoshi Shimizu
Original Article

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.

Keywords

Chemotherapy Pancreatic neoplasms Radiotherapy Gemcitabine S-1 

Notes

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.

References

  1. 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 38:641–648CrossRefPubMedGoogle Scholar
  2. 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 2:865–867CrossRefPubMedGoogle Scholar
  3. 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 48:1705–1710CrossRefPubMedGoogle Scholar
  4. 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 80:751–755CrossRefGoogle Scholar
  5. 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 19:1592–1599CrossRefPubMedGoogle Scholar
  6. 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 4506Google Scholar
  7. 7.
    Liu RC, Traverso LW (2005) Diagnostic laparoscopy improves staging of pancreatic cancer deemed locally unresectable by computed tomography. Surg Endosc 19:638–642CrossRefPubMedGoogle Scholar
  8. 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 8:1068–1071CrossRefPubMedGoogle Scholar
  9. 9.
    Jimenez RE, Warshaw AL, Fernandez-Del Castillo C (2000) Laparoscopy and peritoneal cytology in the staging of pancreatic cancer. J Hepatobiliary Pancreat Surg 7:15–20CrossRefPubMedGoogle Scholar
  10. 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), LBA4513Google Scholar
  11. 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 4514Google Scholar
  12. 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 61:615–621CrossRefPubMedGoogle Scholar
  13. 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 94:1575–1579PubMedGoogle Scholar
  14. 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 4550Google Scholar
  15. 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 69:421–427CrossRefPubMedGoogle Scholar
  16. 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 86:1551–1554CrossRefPubMedGoogle Scholar
  17. 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 17:2208–2212PubMedGoogle Scholar
  18. 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 54:1575–1578PubMedGoogle Scholar
  19. 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 7:2246–2253PubMedGoogle Scholar
  20. 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 28:345–350CrossRefPubMedGoogle Scholar
  21. 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 68:809–816PubMedGoogle Scholar
  22. 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 26:1080–1085CrossRefPubMedGoogle Scholar
  23. 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 92:481–486PubMedGoogle Scholar
  24. 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 97:464–471CrossRefPubMedGoogle Scholar
  25. 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 25:326–331CrossRefPubMedGoogle Scholar
  26. 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 110:47–55CrossRefPubMedGoogle Scholar
  27. 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 24:3946–3952CrossRefPubMedGoogle Scholar
  28. 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 23:3509–3516CrossRefPubMedGoogle Scholar
  29. 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 68:801–808PubMedGoogle Scholar
  30. 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 26:942–947CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Kohei Nakachi
    • 1
  • Junji Furuse
    • 4
  • Taira Kinoshita
    • 2
  • Mitsuhiko Kawashima
    • 3
  • Hiroshi Ishii
    • 5
  • Masafumi Ikeda
    • 1
  • Shuichi Mitsunaga
    • 1
  • Satoshi Shimizu
    • 1
  1. 1.Divisions of Hepatobiliary and Pancreatic OncologyNational Cancer Center Hospital EastKashiwaJapan
  2. 2.Division of Upper Abdominal SurgeryNational Cancer Center Hospital EastKashiwaJapan
  3. 3.Division of Radiation OncologyNational Cancer Center Hospital EastKashiwaJapan
  4. 4.Department of Internal Medicine, Medical OncologyKyorin University School of MedicineTokyoJapan
  5. 5.Department of GastroenterologyCancer Institute HospitalTokyoJapan

Personalised recommendations