Advertisement

Cancer Chemotherapy and Pharmacology

, Volume 73, Issue 4, pp 665–671 | Cite as

A prospective phase II trial of S-1 and cisplatin-based chemoradiotherapy for locoregionally advanced esophageal cancer

  • Hyun Chang
  • Sung Kwan Shin
  • Byoung Chul Cho
  • Chang-Geol Lee
  • Choong Bai Kim
  • Dae Joon Kim
  • Jin Gu Lee
  • Jin Hur
  • Chang Young Lee
  • Mi Kyung Bae
  • Hye Ryun Kim
  • Sang Kil Lee
  • Jun Chul Park
  • Hyuk Lee
  • Hyoung-Il Kim
  • Hyunsoo Chung
  • Jihye Cha
  • Yong Chan LeeEmail author
  • Joo-Hang KimEmail author
Original Article

Abstract

Purpose

S-1 is a novel oral fluoropyrimidine anticancer agent designed to enhance clinical efficacy, reduce gastrointestinal toxicity, and enhance radiotherapy effectiveness. A phase II trial was conducted to evaluate the efficacy and safety of preoperative chemoradiation with S-1 and cisplatin in locoregionally advanced esophageal cancer.

Methods

Eligible patients had stage IIA-IVA esophageal cancer. Patients received two cycles of S-1 (days 1–14 and days 22–35) and cisplatin (days 1 and 22) with concurrent radiotherapy (50.4 Gy total; 1.8 Gy/fraction). Esophagectomy was performed between weeks 12 and 18 as determined by the specialist multidisciplinary team.

Results

Sixty patients were enrolled in this study between March 2008 and August 2011, and 59 were eligible. The clinical stage was ≥T3 in 28 patients (47 %) and N1 in 43 patients (72 %), with squamous cell carcinoma histology in 58 patients (97 %). Fifty-four patients (90 %) completed the planned chemoradiation. After chemoradiation, the clinical tumor response rate was 64.4 %. The primary toxicities included neutropenia (24 %) and esophagitis (8.5 %). Three treatment-related deaths were noted. Twenty-five patients (42 %) underwent esophagectomy following chemoradiation, and 15 achieved complete pathologic regression. The estimated overall survival and progression-free survival rates after 2 years were 65 and 48 %, respectively.

Conclusions

Concurrent chemoradiation with S-1 and cisplatin exhibited encouraging results with complete pathologic regression. The survival data were promising compared with the historical data of 5FU/cisplatin and should be confirmed in a randomized phase III trial. Toxicities were significant but clinically manageable.

Keywords

S-1 Cisplatin Esophageal cancer Chemoradiotherapy Preoperative 

Notes

Acknowledgments

We are grateful to Miss. Suji Shin for administrative help for this study.

Conflict of interest

The authors made no disclosures.

References

  1. 1.
    Tepper J, Krasna MJ, Niedzwiecki D et al (2008) Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol 26:1086–1092PubMedCrossRefGoogle Scholar
  2. 2.
    Burmeister BH, Smithers BM, Gebski V et al (2005) Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol 6:659–668PubMedCrossRefGoogle Scholar
  3. 3.
    Lv J, Cao XF, Zhu B, Ji L, Tao L, Wang DD (2009) Effect of neoadjuvant chemoradiotherapy on prognosis and surgery for esophageal carcinoma. World J Gastroenterol 15:4962–4968PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Lee SJ, Ahn BM, Kim JG et al (2009) Definitive chemoradiotherapy with capecitabine and cisplatin in patients with esophageal cancer: a pilot study. J Korean Med Sci 24:120–125PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Harada K, Kawaguchi S, Supriatno H, Kawashima Y, Yoshida H, Sato M (2005) S-1, an oral fluoropyrimidine anti-cancer agent, enhanced radiosensitivity in a human oral cancer cell line in vivo and in vitro: involvement possibility of inhibition of survival signal, Akt/PKB. Cancer Lett 226:161–168PubMedCrossRefGoogle Scholar
  6. 6.
    Nakata E, Fukushima M, Takai Y et al (2006) S-1, an oral fluoropyrimidine, enhances radiation response of DLD-1/FU human colon cancer xenografts resistant to 5-FU. Oncol Rep 16:465–471PubMedGoogle Scholar
  7. 7.
    Yokota T, Onozawa Y, Boku N et al (2011) S-1 monotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck after progression on platinum-based chemotherapy. Jpn J Clin Oncol 41:1351–1357PubMedCrossRefGoogle Scholar
  8. 8.
    Cho SH, Shim HJ, Lee SR et al (2008) Concurrent chemoradiotherapy with S-1 and cisplatin in advanced esophageal cancer. Dis Esophagus 21:697–703PubMedCrossRefGoogle Scholar
  9. 9.
    Bedenne L, Michel P, Bouche O et al (2007) Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 25:1160–1168PubMedCrossRefGoogle Scholar
  10. 10.
    Koo DH, Park SI, Kim YH et al (2012) Phase II study of use of a single cycle of induction chemotherapy and concurrent chemoradiotherapy containing capecitabine/cisplatin followed by surgery for patients with resectable esophageal squamous cell carcinoma: long-term follow-up data. Cancer Chemother Pharmacol 69:655–663PubMedCrossRefGoogle Scholar
  11. 11.
    van Hagen P, Hulshof MC, van Lanschot JJ et al (2012) Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366:2074–2084PubMedCrossRefGoogle Scholar
  12. 12.
    Herskovic A, Martz K, Al-Sarraf M et al (1992) Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 326:1593–1598PubMedCrossRefGoogle Scholar
  13. 13.
    Forastiere AA, Orringer MB, Perez-Tamayo C, Urba SG, Zahurak M (1993) Preoperative chemoradiation followed by transhiatal esophagectomy for carcinoma of the esophagus: final report. J Clin Oncol 11:1118–1123PubMedGoogle Scholar
  14. 14.
    Donahue JM, Nichols FC, Li Z et al (2009) Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg 87:392–398 discussion 8–9PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Courrech Staal EF, Aleman BM, Boot H, van Velthuysen ML, van Tinteren H, van Sandick JW (2010) Systematic review of the benefits and risks of neoadjuvant chemoradiation for oesophageal cancer. Br J Surg 97:1482–1496PubMedCrossRefGoogle Scholar
  16. 16.
    Kim MK, Cho KJ, Park SI et al (2009) Initial stage affects survival even after complete pathologic remission is achieved in locally advanced esophageal cancer: analysis of 70 patients with pathologic major response after preoperative chemoradiotherapy. Int J Radiat Oncol Biol Phys 75:115–121PubMedCrossRefGoogle Scholar
  17. 17.
    Reynolds JV, Muldoon C, Hollywood D et al (2007) Long-term outcomes following neoadjuvant chemoradiotherapy for esophageal cancer. Ann Surg 245:707–716PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Stahl M, Walz MK, Stuschke M et al (2009) Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol 27:851–856PubMedCrossRefGoogle Scholar
  19. 19.
    Medical Research Council Oesophageal Cancer Working G (2002) Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 359:1727–1733CrossRefGoogle Scholar
  20. 20.
    Lee JL, Park SI, Kim SB et al (2004) A single institutional phase III trial of preoperative chemotherapy with hyperfractionation radiotherapy plus surgery versus surgery alone for resectable esophageal squamous cell carcinoma. Ann Oncol 15:947–954PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Hyun Chang
    • 1
    • 7
    • 8
  • Sung Kwan Shin
    • 2
    • 8
  • Byoung Chul Cho
    • 1
    • 8
  • Chang-Geol Lee
    • 3
    • 8
  • Choong Bai Kim
    • 4
    • 8
  • Dae Joon Kim
    • 5
    • 8
  • Jin Gu Lee
    • 5
    • 8
  • Jin Hur
    • 6
    • 8
  • Chang Young Lee
    • 5
    • 8
  • Mi Kyung Bae
    • 5
    • 8
  • Hye Ryun Kim
    • 1
    • 8
  • Sang Kil Lee
    • 2
    • 8
  • Jun Chul Park
    • 2
    • 8
  • Hyuk Lee
    • 2
    • 8
  • Hyoung-Il Kim
    • 4
    • 8
  • Hyunsoo Chung
    • 2
    • 8
  • Jihye Cha
    • 6
    • 8
  • Yong Chan Lee
    • 2
    • 8
    Email author
  • Joo-Hang Kim
    • 1
    • 8
    Email author
  1. 1.Yonsei Cancer CenterYonsei University Health SystemSeoulRepublic of Korea
  2. 2.Division of Gastroenterology, Department of Internal MedicineYonsei University College of MedicineSeoulRepublic of Korea
  3. 3.Department of Radiation OncologyYonsei University College of MedicineSeoulRepublic of Korea
  4. 4.Department of SurgeryYonsei University College of MedicineSeoulRepublic of Korea
  5. 5.Department of Thoracic and Cardiovascular SurgeryYonsei University College of MedicineSeoulRepublic of Korea
  6. 6.Department of RadiologyYonsei University College of MedicineSeoulRepublic of Korea
  7. 7.Department of Internal MedicineSeoul National University Bundang HospitalSeongnam-siRepublic of Korea
  8. 8.Esophageal Cancer Special ClinicYonsei University College of MedicineSeoulRepublic of Korea

Personalised recommendations