Skip to main content

Advertisement

SpringerLink
Log in

Conversion surgery after combination chemotherapy of docetaxel, cisplatin and S-1 (DCS) for far-advanced gastric cancer

  • Original Article
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Purpose

A triplet regimen of docetaxel, cisplatin, and S-1(DCS) is highly effective against metastatic gastric cancer. We performed this study to clarify the safety and efficacy of surgical resection in patients with initially unresectable gastric cancer, after down-staging or disease control was achieved by DCS chemotherapy.

Methods

The subjects of this retrospective study were 31 consecutive patients with initially unresectable gastric cancer, who underwent surgical resection between October, 2006 and December, 2012, after down-staging or disease control was achieved by DCS chemotherapy. We evaluated the clinicopathological factors and clinical outcomes and assessed radiographic response based on the RECIST criteria, not by central review.

Result

Before DCS chemotherapy, 18 patients had extra-regional lymph node metastasis, 5 had liver metastasis, 8 had macroscopic peritoneal metastasis, and 8 had pancreatic head invasion. Twenty-three (74.2%) of the 31 patients underwent R0 resection. Postoperative morbidity and mortality rates were 16.1 and 0%. During chemotherapy, grade 3/4 toxicities included neutropenia (54.8%), leukopenia (32.3%), and anemia (16.1%). Median progression-free survival and median overall survival (OS) were 42.1 and 56.1 months, respectively. These results were similar for all patients, except those with locally advanced disease alone. In the multivariate analysis for OS, ypN remained an independent negative prognostic factor (p = 0.018).

Conclusion

Surgical resection after DCS chemotherapy for initially unresectable gastric cancer was safe and provided a reasonable R0 resection rate and good mid-term survival.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–E86.

    Article  CAS  PubMed  Google Scholar 

  2. Nashimoto A, Akazawa K, Isobe Y, Miyashiro I, Katai H, Kodera Y, et al. Gastric cancer treated in 2002 in Japan: 2009 annual report of the JGCA nationwide registry. Gastric Cancer. 2013;16:1–27.

    Article  PubMed  Google Scholar 

  3. Fujitani K. Overview of adjuvant and neoadjuvant therapy for resectable gastric cancer in the East. Dig Surg. 2013;30:119–29.

    Article  CAS  PubMed  Google Scholar 

  4. Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29:4387–93.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008;9:215–21.

    Article  CAS  PubMed  Google Scholar 

  7. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006;24:4991–7.

    Article  PubMed  Google Scholar 

  8. Bissery MC, Vrignaud P, Lavelle F. Preclinical profile of docetaxel (taxotere): efficacy as a single agent and in combination. Semin Oncol. 1995;22:3–16.

    CAS  Google Scholar 

  9. Shirasaka T, Shimamato Y, Ohshimo H, Yamaguchi M, Kato T, Yonekura K, et al. 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. 1996;7:548–57.

    Article  CAS  PubMed  Google Scholar 

  10. Takechi T, Fujioka A, Matsushima E, Fukushima M. Enhancement of the antitumour activity of 5-fluorouracil (5-FU) by inhibiting dihydropyrimidine dehydrogenase activity (DPD) using 5-chloro-2,4-dihydroxypyridine (CDHP) in human tumour cells. Eur J Cancer. 2002;38:1271–7.

    Article  CAS  PubMed  Google Scholar 

  11. Shirasaka T, Shimamoto Y, Fukushima M. Inhibition by oxonic acid of gastrointestinal toxicity of 5-fluorouracil without loss of its antitumor activity in rats. Cancer Res. 1993;53:4004–9.

    CAS  PubMed  Google Scholar 

  12. Koizumi W, Nakayama N, Tanabe S, Sasaki T, Higuchi K, Nishimura K, et al. A multicenter phase II study of combined chemotherapy with docetaxel, cisplatin, and S-1 in patients with unresectable or recurrent gastric cancer (KDOG 0601). Cancer Chemother Pharmacol. 2012;69:407–13.

    Article  CAS  PubMed  Google Scholar 

  13. Sym SJ, Chang HM, Ryu MH, Lee JL, Kim TW, Yook JH, et al. Neoadjuvant docetaxel, capecitabine and cisplatin (DXP) in patients with unresectable locally advanced or metastatic gastric cancer. Ann Surg Oncol. 2010;17:1024–32.

    Article  PubMed  Google Scholar 

  14. Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13:176–81.

    Article  PubMed  Google Scholar 

  15. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  PubMed  Google Scholar 

  16. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–96.

    Article  PubMed  Google Scholar 

  17. Katayama H, Kurokawa Y, Nakamura K, Ito H, Kanemitsu Y, Masuda N, et al. Extended Clavien-Dindo classification of surgical complications: Japan Clinical Oncology Group postoperative complications criteria. Surg Today. 2016;46:668–85.

    Article  PubMed  Google Scholar 

  18. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma. 3rd English edition. Gastric Cancer. 2011;14:101–12.

  19. Kurokawa Y, Shibata T, Sasako M, Sano T, Tsuburaya A, Iwasaki Y, et al. Validity of response assessment criteria in neoadjuvant chemotherapy for gastric cancer (JCOG0507-A). Gastric Cancer. 2014;17:514–21.

    Article  CAS  PubMed  Google Scholar 

  20. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.

    Article  CAS  PubMed  Google Scholar 

  21. Hirakawa M, Sato Y, Ohnuma H, Takayama T, Sagawa T, Nobuoka T, et al. A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker. Cancer Chemother Pharmacol. 2013;71:789–97.

    Article  CAS  PubMed  Google Scholar 

  22. Lowy AM, Mansfield PF, Leach SD, Pazdur R, Dumas P, Ajani JA. Response to neoadjuvant chemotherapy best predicts survival after curative resection of gastric cancer. Ann Surg. 1999;229:303–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Oki E, Emi Y, Kusumoto T, Sakaguchi Y, Yamamoto M, Sadanaga N, et al. Phase II Study of Docetaxel and S-1 (DS) as Neoadjuvant Chemotherapy for Clinical Stage III Resectable Gastric Cancer. Ann Surg Oncol 2014;21:2340–6.

    Article  PubMed  Google Scholar 

  24. Tsuburaya A, Mizusawa J, Tanaka Y, Fukushima N, Nashimoto A, Sasako M, et al. Neoadjuvant chemotherapy with S-1 and cisplatin followed by D2 gastrectomy with para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis. Br J Surg. 2014;101:653–60.

    Article  CAS  PubMed  Google Scholar 

  25. Ito S, Sano T, Mizusawa J, Takahari D, Katayama H, Katai H, et al. A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002. Gastric Cancer. 2017;20:322–31.

    Article  CAS  PubMed  Google Scholar 

  26. Yoshikawa T, Sasako M, Yamamoto S, Sano T, Imamura H, Fujitani K, et al. Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer. Br J Surg. 2009;96:1015–22.

    Article  CAS  PubMed  Google Scholar 

  27. Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, et al. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009;10:1063–9.

    Article  CAS  PubMed  Google Scholar 

  28. Han DS, Suh YS, Kong SH, Lee HJ, Im SA, Bang YJ, et al. Outcomes of surgery aiming at curative resection in good responder to induction chemotherapy for gastric cancer with distant metastases. J Surg Oncol. 2013;107:511–6.

    Article  PubMed  Google Scholar 

  29. Ishigami S, Natsugoe S, Nakajo A, Matsumoto M, Uenosono Y, Arigami T, et al. Salvage gastrectomy following a combination of biweekly paclitaxel and S-1 for stage IV gastric cancer. J Gastrointest Surg. 2008;12:1370–5.

    Article  PubMed  Google Scholar 

  30. Yabusaki H, Nashimoto A, Matsuki A, Aizawa M. Significance of surgical treatment in multimodal therapy for stage IV highly advanced gastric cancer. Hepatogastroenterology. 2013;60:377–81.

    PubMed  Google Scholar 

  31. Yano M, Shiozaki H, Inoue M, Tamura S, Doki Y, Yasuda T, et al. Neoadjuvant chemotherapy followed by salvage surgery: effect on survival of patients with primary noncurative gastric cancer. World J Surg. 2002;26:1155–9.

    Article  PubMed  Google Scholar 

  32. Terashima M. Conversion therapy for gastric cancer: who can make conversion as successful as Goromaru? Gastric Cancer. 2016;19:685–6.

    Article  PubMed  Google Scholar 

  33. Yoshida K, Yamaguchi K, Okumura N, Osada S, Takahashi T, Tanaka Y, et al. The roles of surgical oncologists in the new era: minimally invasive surgery for early gastric cancer and adjuvant surgery for metastatic gastric cancer. Pathobiology. 2011;78:343–52.

    Article  CAS  PubMed  Google Scholar 

  34. Yoshida K, Yamaguchi K, Okumura N, Tanahashi T, Kodera Y. Is conversion therapy possible in stage IV gastric cancer: the proposal of new biological categories of classification. Gastric Cancer. 2016;19:329–38.

    Article  PubMed  Google Scholar 

  35. Mansour JC, Tang L, Shah M, Bentrem D, Klimstra DS, Gonen M, et al. Does graded histologic response after neoadjuvant chemotherapy predict survival for completely resected gastric cancer? Ann Surg Oncol. 2007;14:3412–8.

    Article  PubMed  Google Scholar 

  36. Koh YW, Park YS, Ryu MH, Ryoo BY, Park HJ, Yook JH, et al. Postoperative nodal status and diffuse-type histology are independent prognostic factors in resectable advanced gastric carcinomas after preoperative chemotherapy. Am J Surg Pathol. 2013;37:1022–9.

    Article  PubMed  Google Scholar 

  37. Ojima T, Nakamori M, Nakamura M, Katsuda M, Hayata K, Nakamura Y, et al. Expression of BRCA1, a factor closely associated with relapse-free survival, in patients who underwent neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil for squamous cell carcinoma of the esophagus. Surg Today. 2017;47:65–73.

    Article  CAS  PubMed  Google Scholar 

  38. Wada N, Kurokawa Y, Miyazaki Y, Makino T, Takahashi T, Yamasaki M, et al. The characteristics of the serum carcinoembryonic antigen and carbohydrate antigen 19–9 levels in gastric cancer cases. Surg Today. 2017;47:227–32.

    Article  CAS  PubMed  Google Scholar 

  39. Fields RC, Strong VE, Gonen M, Goodman KA, Rizk NP, Kelsen DP, et al. Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma. Br J Cancer. 2011;104:1840–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Cho H, Nakamura J, Asaumi Y, Yabusaki H, Sakon M, Takasu N, et al. Long-term survival outcomes of advanced gastric cancer patients who achieved a pathological complete response with neoadjuvant chemotherapy: a systematic review of the literature. Ann Surg Oncol. 2015;22:787–92.

    Article  PubMed  Google Scholar 

  41. Yoshikawa T, Tanabe K, Nishikawa K, Ito Y, Matsui T, Kimura Y, et al. Induction of a pathological complete response by four courses of neoadjuvant chemotherapy for gastric cancer: early results of the randomized phase II COMPASS trial. Ann Surg Oncol. 2014;21:213–9.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan

    Hiroaki Mieno, Keishi Yamashita, Kei Hosoda, Hiromitsu Moriya, Natsuya Katada & Masahiko Watanabe

  2. Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan

    Katsuhiko Higuchi, Mizutomo Azuma, Satoshi Tanabe & Wasaburo Koizumi

  3. Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Japan

    Shouko Komori

  4. Department of Pathology, Kitasato University School of Medicine, Sagamihara, Japan

    Tsutomu Yoshida

Authors
  1. Hiroaki Mieno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keishi Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kei Hosoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiromitsu Moriya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Katsuhiko Higuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mizutomo Azuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shouko Komori
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tsutomu Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Satoshi Tanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wasaburo Koizumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Natsuya Katada
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Masahiko Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroaki Mieno.

Ethics declarations

Conflict of interest

We have no conflicts of interest to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mieno, H., Yamashita, K., Hosoda, K. et al. Conversion surgery after combination chemotherapy of docetaxel, cisplatin and S-1 (DCS) for far-advanced gastric cancer. Surg Today 47, 1249–1258 (2017). https://doi.org/10.1007/s00595-017-1512-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-017-1512-z

Keywords

Search

Navigation