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Phase II Trial of Adjuvant Chemotherapy with S-1 for Colorectal Liver Metastasis

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

This phase II trial was designed to evaluate the safety and efficacy of adjuvant chemotherapy with S-1 in patients with curatively resected liver metastasis from colorectal cancer. Results of an interim analysis of safety and short-term outcomes are reported.

Methods

Patients who underwent curative resection of liver metastasis from colorectal cancer received S-1 monotherapy (on days 1–28, followed by 14 days’ rest, 8 cycles) as adjuvant chemotherapy.

Results

Among 62 patients enrolled between October 2008 and August 2010, a total of 60 patients were eligible for analysis. The most frequent grade 3 or higher hematologic toxicity involved neutropenia in three patients (5.0 %). Nonhematologic toxicities of grade 3 or higher were fatigue in 6.7 % of patients. Grade 4 enteritis occurred in one patient, but resolved promptly after withdrawal of S-1 therapy. The completion rate of the eight scheduled cycles of chemotherapy was 58.3 %. The most common reasons for withdrawal of treatment was the detection of early relapse in 16 patients (64 %). When the 16 patients who had recurrence during adjuvant treatment were excluded from analysis, 79.5 % of the remaining 44 patients completed the scheduled treatment. Early recurrence within 1 year after curative liver resection occurred in 21 patients (35 %). The most common site was the remnant liver in 14 patients.

Conclusions

Orally administered S-1 after curative liver resection has an acceptable toxicity profile and a high rate of completion of the therapy. S-1 can be safely used and might be a viable treatment option in an adjuvant setting.

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References

  1. Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009;27:3677–83.

    Google Scholar 

  2. Nathan H, de Jong MC, Pulitano C, et al. Conditional survival after surgical resection of colorectal liver metastasis: an international multi-institutional analysis of 949 patients. J Am Coll Surg. 2010;210:755–64.

    Article  PubMed  Google Scholar 

  3. Haller DG, Catalano PJ, Macdonald JS, et al. Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089. J Clin Oncol. 2005;23:8671–8.

    Article  PubMed  Google Scholar 

  4. Wolmark N, Rockette H, Mamounas E, et al. Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes’ B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04. J Clin Oncol. 1999;17:3553–9.

    PubMed  CAS  Google Scholar 

  5. André T, Quinaux E, Louvet C, et al. Phase III study comparing a semimonthly with a monthly regimen of fluorouracil and leucovorin as adjuvant treatment for stage II and III colon cancer patients: final results of GERCOR C96.1. J Clin Oncol. 2007;25:3732–8.

    Article  PubMed  Google Scholar 

  6. Twelves C, Wong A, Nowacki MP, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005;352:2696–704.

    Article  PubMed  CAS  Google Scholar 

  7. Lembersky BC, Wieand HS, Petrelli NJ, et al. Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol. 2006;24:2059–64.

    Article  PubMed  CAS  Google Scholar 

  8. André T, Boni C, Mounedji-Boudiaf L, et al. Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350:2343–51.

    Article  PubMed  Google Scholar 

  9. Kuebler JP, Wieand HS, O’Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007;25:2198–204.

    Article  PubMed  CAS  Google Scholar 

  10. Haller DG, Tabernero J, Maroun J, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011;29:1465–71.

    Article  PubMed  CAS  Google Scholar 

  11. Watanabe T, Itabashi M, Shimada Y, et al. Japanese Society for Cancer of the Colon and Rectum. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer. Int J Clin Oncol. 2012;17:1–29.

    Article  PubMed  Google Scholar 

  12. Hamaguchi T, Shirao K, Moriya Y, Yoshida S, Kodaira S, Ohashi Y; NSAS-CC Group. Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC). Cancer Chemother Pharmacol. 2011;67:587–96.

    Article  PubMed  CAS  Google Scholar 

  13. Portier G, Elias D, Bouche O, et al. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol. 2006;24:4976–82.

    Article  PubMed  CAS  Google Scholar 

  14. Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008;371:1007–16.

    Article  PubMed  CAS  Google Scholar 

  15. Ychou M, Hohenberger W, Thezenas S, et al. A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. Ann Oncol. 2009;20:1964–70.

    Article  PubMed  CAS  Google Scholar 

  16. Ohtsu A, Baba H, Sakata Y, et al. Phase II study of S-1, a novel oral fluorophyrimidine derivative, in patients with metastatic colorectal carcinoma. S-1 Cooperative Colorectal Carcinoma Study Group. Br J Cancer. 2000;83:141–5.

    Article  PubMed  CAS  Google Scholar 

  17. Shirao K, Ohtsu A, Takada H, et al. Phase II study of oral S-1 for treatment of metastatic colorectal carcinoma. Cancer. 2004;100:2355–61.

    Article  PubMed  CAS  Google Scholar 

  18. Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20.

    Article  Google Scholar 

  19. Japanese Society for Cancer of the Colon and Rectum. Japanese classification of colorectal carcinoma. 2nd English edition. Tokyo: Kanehara; 2009.

    Google Scholar 

  20. Sobin LH, Wittekind C. TNM classification of malignant tumours 6th edition. New York: Wiley.

  21. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. Colon cancer v.2. 2012. http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed 29 Jan 2012.

  22. Mitry E, Fields AL, Bleiberg H, et al. Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol. 2008;26:4906–11.

    Article  PubMed  CAS  Google Scholar 

  23. Sakamoto J, Ohashi Y, Hamada C, et al. Efficacy of oral adjuvant therapy after resection of colorectal cancer:5-year results from three randomized trials. J Clin Oncol. 2004;22:484–92.

    PubMed  Google Scholar 

  24. Tsukuda M, Kida A, Fujii M, et al. Chemotherapy Study Group of Head and Neck Cancer. Randomized scheduling feasibility study of S-1 for adjuvant chemotherapy in advanced head and neck cancer. Br J Cancer. 2005;93:884–9.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

We are grateful to many other participants of the Nagoya Surgical Oncology Group during the study.

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Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Keisuke Uehara MD, PhD, Yu Takahashi MD, PhD, Tomoki Ebata MD, PhD & Masato Nagino MD, PhD

  2. Department of Surgery, Ogaki Municipal Hospital, Gifu, Japan

    Atsuyuki Maeda MD, PhD

  3. Department of Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan

    Eiji Sakamoto MD, PhD

  4. Department of Surgery, Toyohashi Municipal Hospital, Aichi, Japan

    Kazuhiro Hiramatsu MD, PhD

  5. Department of Surgery, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan

    Eiji Takeuchi MD, PhD

  6. Department of Surgery, Chubu Rosai Hospital, Nagoya, Japan

    Kenji Sakaguchi MD, PhD

  7. Department of Surgery, Chukyo Hospital, Nagoya, Japan

    Yuichiro Tojima MD, PhD

Authors
  1. Keisuke Uehara MD, PhD
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  2. Atsuyuki Maeda MD, PhD
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  3. Eiji Sakamoto MD, PhD
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  4. Kazuhiro Hiramatsu MD, PhD
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  5. Eiji Takeuchi MD, PhD
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  6. Kenji Sakaguchi MD, PhD
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  7. Yuichiro Tojima MD, PhD
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  8. Yu Takahashi MD, PhD
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  9. Tomoki Ebata MD, PhD
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  10. Masato Nagino MD, PhD
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Corresponding author

Correspondence to Keisuke Uehara MD, PhD.

Additional information

This study was conducted for the Nagoya Surgical Oncology Group.

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Uehara, K., Maeda, A., Sakamoto, E. et al. Phase II Trial of Adjuvant Chemotherapy with S-1 for Colorectal Liver Metastasis. Ann Surg Oncol 20, 475–481 (2013). https://doi.org/10.1245/s10434-012-2665-z

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  • DOI: https://doi.org/10.1245/s10434-012-2665-z

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