A multicenter phase II study of gemcitabine and S-1 combination chemotherapy in patients with unresectable pancreatic cancer

  • Do-Youn Oh
  • Yongjun Cha
  • In-Sil Choi
  • So-Young Yoon
  • In Keun Choi
  • Jee Hyun Kim
  • Sang Cheul Oh
  • Chang Duck Kim
  • Jae Sun Kim
  • Yung-Jue Bang
  • Yeul Hong Kim
Original Article

Abstract

Purpose

To confirm the efficacy and toxicity of gemcitabine and S-1 combination chemotherapy when used as a first-line therapy in patients with unresectable pancreatic cancer.

Methods

Patients with locally advanced or metastatic or recurrent pancreatic adenocarcinoma, which was histologically or cytologically proven, with at least one measurable lesion were eligible for the study. Gemcitabine at a dose of 1,000 mg/m2 was intravenously given over 30 min on days 1 and 8, while S-1 at a dose of 40 mg/m2 was orally given twice daily from day 1 to 14, and the cycle was repeated every 3 weeks. The objective response rate, which was assessed according to RECIST criteria, was the primary end point.

Results

A total of 38 patients were enrolled between June 2006 and June 2007. The median number of treatment courses was 5.5 (range 1–22). Thirty-four patients were evaluable for response. Although no complete response was seen, partial responses were achieved in 11 patients, resulting in an overall response rate of 32% [95% confidence interval (CI) 17–48%]. The median response duration was 6.0 months (95% CI 4.6–8.3 months), the median time-to-progression was 5.4 months (95% CI 2.9–8.0 months), and the median overall survival was 8.4 months (95% CI 5.7–11.1 months). The major grade 3/4 hematologic toxicities were neutropenia (39.5%), leukopenia (15.8%), thrombocytopenia (2.6%), and anemia (7.9%). The major grade 3/4 non-hematologic toxicities included anorexia (10.5%), stomatitis (2.6%), rash (7.9%), fatigue (7.9%) and hyperbilirubinemia (5.3%).

Conclusions

Gemcitabine and S-1 combination chemotherapy was effective and tolerable in patients with unresectable pancreatic cancer.

Keywords

Gemcitabine S-1 Pancreatic cancer Palliative 

Notes

Acknowledgment

S-1 was kindly supplied by Jeil Pharm. Co., Ltd.

Conflict of interest statement

None declared.

References

  1. 1.
    Shin HR, Won YJ, Jung KW et al (2005) Nationwide cancer incidence in Korea, 1999–2001; first result using the National Cancer Incidence Database. Cancer Res Treat 37:325–331CrossRefPubMedGoogle Scholar
  2. 2.
    Burris HA 3rd, Moore MJ, Andersen J et al (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 15:2403–2413PubMedGoogle Scholar
  3. 3.
    Berlin JD, Catalano P, Thomas JP, Kugler JW, Haller DG, Benson AB 3rd (2002) Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 20:3270–3275CrossRefPubMedGoogle Scholar
  4. 4.
    Bramhall SR, Schulz J, Nemunaitis J, Brown PD, Baillet M, Buckels JA (2002) A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer. Br J Cancer 87:161–167CrossRefPubMedGoogle Scholar
  5. 5.
    Colucci G, Giuliani F, Gebbia V et al (2002) Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell’Italia Meridionale. Cancer 94:902–910CrossRefPubMedGoogle Scholar
  6. 6.
    Oettle H, Richards D, Ramanathan RK et al (2005) A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer. Ann Oncol 16:1639–1645CrossRefPubMedGoogle Scholar
  7. 7.
    Rocha Lima CM, Green MR, Rotche R et al (2004) Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol 22:3776–3783CrossRefPubMedGoogle Scholar
  8. 8.
    Heinemann V, Quietzsch D, Gieseler F 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
  9. 9.
    Louvet C, Labianca R, Hammel P 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
  10. 10.
    Moore MJ, Goldstein D, Hamm J et al (2007) Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25:1960–1966CrossRefPubMedGoogle Scholar
  11. 11.
    Miksad RA, Schnipper L, Goldstein M (2007) Does a statistically significant survival benefit of erlotinib plus gemcitabine for advanced pancreatic cancer translate into clinical significance and value? J Clin Oncol 25:4506–4507 (author reply 4508)CrossRefPubMedGoogle Scholar
  12. 12.
    Herrmann R, Bodoky G, Ruhstaller T et al (2007) Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol 25:2212–2217CrossRefPubMedGoogle Scholar
  13. 13.
    Bernhard J, Dietrich D, Scheithauer W et al (2008) Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial—SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol 26:3695–3701CrossRefPubMedGoogle Scholar
  14. 14.
    Cunningham D, Chau I, Stocken D et al (2005) Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. Eur J Cancer 4:Abstract PSIIGoogle Scholar
  15. 15.
    Shirasaka T, Shimamato Y, Ohshimo H et al (1996) Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs 7:548–557CrossRefPubMedGoogle Scholar
  16. 16.
    Takechi T, Nakano K, Uchida J et al (1997) Antitumor activity and low intestinal toxicity of S-1, a new formulation of oral tegafur, in experimental tumor models in rats. Cancer Chemother Pharmacol 39:205–211CrossRefPubMedGoogle Scholar
  17. 17.
    Ueno H, Okusaka T, Ikeda M, Takezako Y, Morizane C (2005) An early phase II study of S-1 in patients with metastatic pancreatic cancer. Oncology 68:171–178CrossRefPubMedGoogle Scholar
  18. 18.
    Okusaka T, Funakoshi A, Furuse J et al (2008) A late phase II study of S-1 for metastatic pancreatic cancer. Cancer Chemother Pharmacol 61:615–621CrossRefPubMedGoogle Scholar
  19. 19.
    Halloran CM, Ghaneh P, Shore S et al (2004) 5-Fluorouracil or gemcitabine combined with adenoviral-mediated reintroduction of p16INK4A greatly enhanced cytotoxicity in Panc-1 pancreatic adenocarcinoma cells. J Gene Med 6:514–525CrossRefPubMedGoogle Scholar
  20. 20.
    Ueno H, Okusaka T, Ikeda M 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
  21. 21.
    Longo DL, Duffey PL, DeVita VT Jr, Wesley MN, Hubbard SM, Young RC (1991) The calculation of actual or received dose intensity: a comparison of published methods. J Clin Oncol 9:2042–2051PubMedGoogle Scholar
  22. 22.
    Ueno H, Okusaka T, Furuse J 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. 2007 ASCO Annual Meeting Proceedings Part I. 25:Abstract No. 4550Google Scholar
  23. 23.
    Lee GW, Kim HJ, Ju JH et al (2009) Phase II trial of S-1 in combination with gemcitabine for chemo-naive patients with locally advanced or metastatic pancreatic cancer. Cancer Chemother Pharmacol (in press)Google Scholar
  24. 24.
    Nakamura K, Yamaguchi T, Ishihara T et al (2005) Phase I trial of oral S-1 combined with gemcitabine in metastatic pancreatic cancer. Br J Cancer 92:2134–2139CrossRefPubMedGoogle Scholar
  25. 25.
    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
  26. 26.
    Kim MK, Lee KH, Jang BI et al (2009) S-1 and gemcitabine as an outpatient-based regimen in patients with advanced or metastatic pancreatic cancer. Jpn J Clin Oncol 39:49–53CrossRefPubMedGoogle Scholar
  27. 27.
    Wong D, Ko AH, Hwang J, Venook AP, Bergsland EK, Tempero MA (2008) Serum CA19-9 decline compared to radiographic response as a surrogate for clinical outcomes in patients with metastatic pancreatic cancer receiving chemotherapy. Pancreas 37:269–274CrossRefPubMedGoogle Scholar
  28. 28.
    Murakami Y, Uemura K, Sudo T et al (2008) Adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma. Am J Surg 195:757–762CrossRefPubMedGoogle Scholar
  29. 29.
    Murakami Y, Uemura K, Sudo T et al (2009) Impact of adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for adenocarcinoma of the body or tail of the pancreas. J Gastrointest Surg 13:85–92Google Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Do-Youn Oh
    • 1
  • Yongjun Cha
    • 1
  • In-Sil Choi
    • 2
  • So-Young Yoon
    • 3
  • In Keun Choi
    • 4
  • Jee Hyun Kim
    • 5
  • Sang Cheul Oh
    • 4
  • Chang Duck Kim
    • 4
  • Jae Sun Kim
    • 4
  • Yung-Jue Bang
    • 1
  • Yeul Hong Kim
    • 4
  1. 1.Department of Internal MedicineSeoul National University College of MedicineSeoulKorea
  2. 2.Department of Internal MedicineSeoul Municipal Boramae HospitalSeoulKorea
  3. 3.Department of Internal MedicineKonkuk University HospitalSeoulKorea
  4. 4.Division of Oncology-Hematology, Department of Internal MedicineKorea University Anam Hospital, Korea University College of MedicineSeoulKorea
  5. 5.Department of Internal MedicineSeoul National University Bundang HospitalSeoulKorea

Personalised recommendations