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The Benefits of Docetaxel Plus Cisplatin and 5-Fluorouracil Induction Therapy in Conversion to Curative Treatment for Locally Advanced Esophageal Squamous Cell Carcinoma

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Abstract

Background

Definitive chemoradiotherapy (CRT), used for treatment of patients with an initial diagnosis of unresectable locally advanced esophageal cancer, has led to unsatisfactory long-term prognosis. Moreover, CRT can lead to esophageal fistula, perforation, and strictures. Therefore, strong induction chemotherapeutic treatments are necessary to reduce the tumor volume for subsequent radical esophagectomy. This study aimed to determine the oncological utility of docetaxel plus cisplatin and 5-fluorouracil (DCF) and the technical feasibility of subsequent esophagectomy for locally advanced esophageal cancer.

Methods

Eighty-seven patients with clinical borderline unresectable T3 and T4 esophageal squamous cell carcinoma without distant metastases were included in this study. There were 44 patients in primary DCF group and 43 patients in definitive CRT group, and perioperative and long-term oncological outcomes were compared between the two groups.

Results

Twenty-two patients (50%) achieved R0 resection in the DCF group. Albeit not significant, the rate of curative treatment was higher in the DCF group than the definitive CRT group (p = 0.099). The overall survival (OS) and progression-free survival (PFS) were better with DCF than with definitive CRT (median OS, 29 vs. 17 months, p = 0.206; median PFS, 10 vs. 6 months, p = 0.020). Specifically, the OS of patients with a Charlson score of less than 3 among the DCF-treated patients tended to be better than those among the definitive CRT-treated patients.

Conclusion

DCF and subsequent esophagectomy achieved R0 resection in 50% of the patients and was associated with better long-term oncological outcomes in patients with initially unresectable esophageal cancer if their systemic status is acceptable.

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References

  1. Rustgi AK, El-Serag HB (2014) Esophageal carcinoma. N Engl J Med 371:2499–2509

    Article  CAS  PubMed  Google Scholar 

  2. Gamliel Z, Krasna MJ (2005) Multimodality treatment of esophageal cancer. Surg Clin North Am 85:621–630

    Article  PubMed  Google Scholar 

  3. Ohtsu A, Boku N, Muro K et al (1999) Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus. J Clin Oncol 17:2915–2921

    Article  CAS  PubMed  Google Scholar 

  4. Matsubara T, Ueda M, Kokudo N et al (2001) Role of esophagectomy in treatment of esophageal carcinoma with clinical evidence of adjacent organ invasion. World J Surg 25:279–284. https://doi.org/10.1007/s002680020060

    Article  CAS  PubMed  Google Scholar 

  5. Markar SR, Karthikesalingam A, Penna M et al (2013) Assessment of short-term clinical outcomes following salvage esophagectomy for the treatment of esophageal malignancy: systematic review and pooled analysis. Ann Surg Oncol 21:922–931

    Article  PubMed  Google Scholar 

  6. Tachimori Y, Kanamori N, Uemura N et al (2009) Salvage esophagectomy after high-dose chemoradiotherapy for esophageal squamous cell carcinoma. J Thorac Cardiovasc Surg 137:49–54

    Article  PubMed  Google Scholar 

  7. Tsushima T, Mizusawa J, Sudo K et al (2016) Risk factors for esophageal fistula associated with chemoradiotherapy for locally advanced unresectable esophageal cancer. Medicine 95:e3699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Okuno T, Wakabayashi M, Kato K et al (2017) Esophageal stenosis and the Glasgow Prognostic Score as independent factors of poor prognosis for patients with locally advanced unresectable esophageal cancer treated with chemoradiotherapy (exploratory analysis of JCOG0303). Int J Clin Oncol 22:1042–1049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ishikura S, Nihei K, Ohtsu A et al (2003) Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus. J Clin Oncol 21:2697–2702

    Article  CAS  PubMed  Google Scholar 

  10. Shimoji H, Karimata H, Nagahama M et al (2013) Induction chemotherapy or chemoradiotherapy followed by radical esophagectomy for T4 esophageal cancer: results of a prospective cohort study. World J Surg 37:2180–2188. https://doi.org/10.1007/s00268-013-2074-x

    Article  PubMed  Google Scholar 

  11. Miyata H, Yamasaki M, Kurokawa Y et al (2012) Clinical relevance of induction triplet chemotherapy for esophageal cancer invading adjacent organs. J Surg Oncol 106:441–447

    Article  PubMed  Google Scholar 

  12. Yokota T, Kato K, Hamamoto Y et al (2016) Phase II study of chemoselection with docetaxel plus cisplatin and 5-fluorouracil induction chemotherapy and subsequent conversion surgery for locally advanced unresectable oesophageal cancer. Br J Cancer 115:1328–1334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Japanese Classification of Esophageal Cancer (2016) 11th Edition: part I. Esophagus 14:1–36

    Google Scholar 

  14. Quan H, Li B, Couris CM et al (2011) Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol 173:676–682

    Article  PubMed  Google Scholar 

  15. Sobin L, Gospodarowicz MWC (eds) (2009) TNM classification of malignant tumours, 7th edn. Wiley-Liss, New York

    Google Scholar 

  16. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247

    Article  CAS  PubMed  Google Scholar 

  17. Thompson WM, Halvorsen RA, Foster WL Jr et al (1983) Computed tomography for staging esophageal and gastroesophageal cancer: reevaluation. AJR Am J Roentgenol 141:951–958

    Article  CAS  PubMed  Google Scholar 

  18. Picus D, Balfe DM, Koehler RE et al (1983) Computed tomography in the staging of esophageal carcinoma. Radiology 146:433–438

    Article  CAS  PubMed  Google Scholar 

  19. Yokota T, Hatooka S, Ura T et al (2011) Docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy for locally advanced borderline-resectable T4 esophageal cancer. Anticancer Res 31:3535–3541

    CAS  PubMed  Google Scholar 

  20. Kaburagi T, Takeuchi H, Kawakubo H et al (2013) Clinical utility of a novel hybrid position combining the left lateral decubitus and prone positions during thoracoscopic esophagectomy. World J Surg 38:410–418. https://doi.org/10.1007/s00268-013-2258-4

    Article  Google Scholar 

  21. Matsuda S, Takeuchi H, Kawakubo H et al (2016) Clinical outcome of transthoracic esophagectomy with thoracic duct resection. Medicine 95:e3839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dindo D, Demartines N, Clavien P-A (2004) Classification of surgical complications. Ann Surg 240:205–213

    Article  PubMed  PubMed Central  Google Scholar 

  23. Takeuchi H, Saikawa Y, Oyama T et al (2009) Factors influencing the long-term survival in patients with esophageal cancer who underwent esophagectomy after chemoradiotherapy. World J Surg 34:277–284. https://doi.org/10.1007/s00268-009-0331-9

    Article  Google Scholar 

  24. Poon LC, Wright D, Rolnik DL et al (2017) Aspirin for evidence-based preeclampsia prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history. Am J Obstet Gynecol 217:585e1–585e5

    Article  CAS  Google Scholar 

  25. Satake H, Tahara M, Mochizuki S et al (2016) A prospective, multicenter phase I/II study of induction chemotherapy with docetaxel, cisplatin and fluorouracil (DCF) followed by chemoradiotherapy in patients with unresectable locally advanced esophageal carcinoma. Cancer Chemother Pharmacol 78:91–99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hara H, Tahara M, Daiko H et al (2013) Phase II feasibility study of preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for esophageal squamous cell carcinoma. Cancer Science 104:1455–1460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Makino T, Yamasaki M, Miyazaki Y et al (2017) Utility of initial induction chemotherapy with 5-fluorouracil, cisplatin, and docetaxel (DCF) for T4 esophageal cancer: a propensity score-matched analysis. Dis Esophagus 31:dox130

    Google Scholar 

  28. Takeuchi H, Miyata H, Gotoh M et al (2014) A risk model for esophagectomy using data of 5354 patients included in a Japanese nationwide web-based database. Ann Surg 260:259–266

    Article  PubMed  Google Scholar 

  29. Takeuchi M, Takeuchi H, Kawakubo H et al (2018) Perioperative risk calculator predicts long-term oncologic outcome for patients with esophageal carcinoma. Ann Surg Oncol 25:837–843

    Article  PubMed  Google Scholar 

  30. Takeuchi M, Kawakubo H, Mayanagi S et al (2018) Postoperative pneumonia is associated with long-term oncologic outcomes of definitive chemoradiotherapy followed by salvage esophagectomy for esophageal cancer. J Gastrointest Surg 22:1881–1889

    Article  PubMed  Google Scholar 

  31. Kataoka K, Takeuchi H, Mizusawa J et al (2017) Prognostic impact of postoperative morbidity after esophagectomy for esophageal cancer. Ann Surg 265:1152–1157

    Article  PubMed  Google Scholar 

  32. Yokota T, Yasuda T, Kato H et al (2018) Concordance of clinical diagnosis of T classification among physicians for locally advanced unresectable thoracic esophageal cancer. Int J Clin Oncol 23:73–80

    Article  PubMed  Google Scholar 

  33. Hamamoto Y, Nojima M, Aoki Y et al (2017) Inter-evaluator heterogeneity of clinical diagnosis for locally advanced esophageal squamous cell carcinoma. Esophagus 14:324–332

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank Kumiko Motooka in the Department of Surgery at Keio University School of Medicine for her help in the preparation of the manuscript.

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Correspondence to Hirofumi Kawakubo.

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Conflict of interest

Yuko Kitagawa have personal fees from sanofi K.K, personal fees from ETHICON PART OF JOHNSON AND JOHNSON FAMILY OF COMPANIES, personal fees from Medtronic Japan Co., Ltd., grants from KYOWA HAKKO KIRIN CO., LTD, outside the submitted work.

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Supplemental Figure 1

(a) Kaplan–Meier curves for overall survival in patients who underwent R1/R2 resection. (b) Kaplan–Meier curves for progression-free survival in patients who underwent R1/R2 resection. (c) Kaplan–Meier curves for overall survival in patients who underwent palliative treatment. (d) Kaplan–Meier curves for progressive-free survival in patients who underwent palliative treatment. Red and blue lines indicate the DCF and definitive CRT groups, respectively. (EPS 377 kb)

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Takeuchi, M., Kawakubo, H., Mayanagi, S. et al. The Benefits of Docetaxel Plus Cisplatin and 5-Fluorouracil Induction Therapy in Conversion to Curative Treatment for Locally Advanced Esophageal Squamous Cell Carcinoma. World J Surg 43, 2006–2015 (2019). https://doi.org/10.1007/s00268-019-05000-3

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  • DOI: https://doi.org/10.1007/s00268-019-05000-3

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