Skip to main content
Erschienen in: Cancer Chemotherapy and Pharmacology 3/2019

08.01.2019 | Original Article

Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for locally advanced esophageal squamous cell carcinoma

verfasst von: Ken Sasaki, Yasuto Uchikado, Itaru Omoto, Takaaki Arigami, Yusaku Osako, Masahiro Noda, Hiroshi Okumura, Kosei Maemura, Ryutaro Higashi, Takashi Yoshiura, Shoji Natsugoe

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To further improve the prognosis of esophageal cancer patients, it is necessary to investigate new treatment strategies. The purposes of this study were to retrospectively assess the safety and efficacy of neoadjuvant chemoradiotherapy (CRT) with docetaxel/cisplatin/5-fluorouracil (DCF) (DCF-RT) in patients with thoracic esophageal squamous cell carcinoma (ESCC).

Methods

We reviewed 30 thoracic ESCC patients who underwent neoadjuvant DCF-RT followed by esophagectomy, and evaluated the safety and efficacy of DCF-RT. DCF-RT consisted of 40 Gy radiation with two courses of intravenous DCF (docetaxel, 30 mg/m2/day, day 1; cisplatin, 7 mg/m2/day, day 1; 5-FU, 350 mg/m2/day, days 1–5 and days 8–12) repeated every 2 weeks. Esophagectomy was scheduled 8–10 weeks after completion of DCF-RT.

Results

Twenty-nine of thirty patients completed radiotherapy; however, 27 of 30 patients required dose reduction of the second cycle of DCF. Complete response (CR), partial response, and stable disease were observed in 7, 11, and 10 patients, respectively. The number of lymph node metastases after DCF-RT was significantly lower than that before DCF-RT (P < 0.0001). Among the 30 patients, pathological CR (pCR) in the primary tumor was observed in 17 patients, and pCRs in both the primary tumor and lymph nodes were observed in 14 patients. The 3-year overall survival rate was 62.2%, and that of patients who experienced pCR was 84%.

Conclusions

Neoadjuvant DCF-RT was tolerable and yielded a high pCR rate in ESCC. Therefore, neoadjuvant DCF-RT may confer a survival benefit and may be a candidate neoadjuvant therapy regimen for patients with locally advanced thoracic ESCC.
Literatur
1.
Zurück zum Zitat Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, Nakamura T, Yabusaki H, Aoyama N, Kurita A (2012) A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol 19(1):68–74CrossRefPubMed Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, Nakamura T, Yabusaki H, Aoyama N, Kurita A (2012) A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol 19(1):68–74CrossRefPubMed
2.
Zurück zum Zitat Hara H, Tahara M, Daiko H, Kato K, Igaki H, Kadowaki S, Tanaka Y, Hamamoto Y, Matsushita H, Nagase M (2013) Phase II feasibility study of preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for esophageal squamous cell carcinoma. Cancer Sci 104(11):1455–1460CrossRefPubMed Hara H, Tahara M, Daiko H, Kato K, Igaki H, Kadowaki S, Tanaka Y, Hamamoto Y, Matsushita H, Nagase M (2013) Phase II feasibility study of preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for esophageal squamous cell carcinoma. Cancer Sci 104(11):1455–1460CrossRefPubMed
3.
Zurück zum Zitat Yamasaki M, Yasuda T, Yano M, Hirao M, Kobayashi K, Fujitani K, Tamura S, Kimura Y, Miyata H, Motoori M (2017) Multicenter randomized phase II study of cisplatin and fluorouracil plus docetaxel (DCF) compared with cisplatin and fluorouracil plus Adriamycin (ACF) as preoperative chemotherapy for resectable esophageal squamous cell carcinoma (OGSG1003). Ann Oncol 28(1):116–120PubMed Yamasaki M, Yasuda T, Yano M, Hirao M, Kobayashi K, Fujitani K, Tamura S, Kimura Y, Miyata H, Motoori M (2017) Multicenter randomized phase II study of cisplatin and fluorouracil plus docetaxel (DCF) compared with cisplatin and fluorouracil plus Adriamycin (ACF) as preoperative chemotherapy for resectable esophageal squamous cell carcinoma (OGSG1003). Ann Oncol 28(1):116–120PubMed
4.
Zurück zum Zitat Higuchi K, Komori S, Tanabe S, Katada C, Azuma M, Ishiyama H, Sasaki T, Ishido K, Katada N, Hayakawa K (2014) Definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) in advanced esophageal cancer: a phase 2 trial (KDOG 0501-P2). Int J Radiat Oncol Biol Phys 89(4):872–879CrossRefPubMed Higuchi K, Komori S, Tanabe S, Katada C, Azuma M, Ishiyama H, Sasaki T, Ishido K, Katada N, Hayakawa K (2014) Definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) in advanced esophageal cancer: a phase 2 trial (KDOG 0501-P2). Int J Radiat Oncol Biol Phys 89(4):872–879CrossRefPubMed
5.
Zurück zum Zitat Okamoto H, Taniyama Y, Sakurai T, Heishi T, Teshima J, Sato C, Maruyama S, Ito K, Onodera Y, Konno-Kumagai T (2018) Definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) for advanced cervical esophageal cancer. Esophagus 15(4):1–5CrossRef Okamoto H, Taniyama Y, Sakurai T, Heishi T, Teshima J, Sato C, Maruyama S, Ito K, Onodera Y, Konno-Kumagai T (2018) Definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) for advanced cervical esophageal cancer. Esophagus 15(4):1–5CrossRef
6.
Zurück zum Zitat van Hagen P, Hulshof M, Van Lanschot J, Steyerberg E, Henegouwen MvB, Wijnhoven B, Richel D, Nieuwenhuijzen G, Hospers G, Bonenkamp J (2012) Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366(22):2074–2084CrossRef van Hagen P, Hulshof M, Van Lanschot J, Steyerberg E, Henegouwen MvB, Wijnhoven B, Richel D, Nieuwenhuijzen G, Hospers G, Bonenkamp J (2012) Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366(22):2074–2084CrossRef
7.
Zurück zum Zitat Nakamura K, Kato K, Igaki H, Ito Y, Mizusawa J, Ando N, Udagawa H, Tsubosa Y, Daiko H, Hironaka S (2013) Three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel, cisplatin plus 5-FU (DCF) versus radiotherapy with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer (JCOG1109, NExT study). Jpn J Clin Oncol 43(7):752–755CrossRefPubMed Nakamura K, Kato K, Igaki H, Ito Y, Mizusawa J, Ando N, Udagawa H, Tsubosa Y, Daiko H, Hironaka S (2013) Three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel, cisplatin plus 5-FU (DCF) versus radiotherapy with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer (JCOG1109, NExT study). Jpn J Clin Oncol 43(7):752–755CrossRefPubMed
8.
Zurück zum Zitat Health UDo, Services H (2009) Common terminology criteria for adverse events (CTCAE) version 4.0. National Institutes of Health, National Cancer Institute 4 (03) Health UDo, Services H (2009) Common terminology criteria for adverse events (CTCAE) version 4.0. National Institutes of Health, National Cancer Institute 4 (03)
10.
Zurück zum Zitat Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibañes E, Pekolj J, Slankamenac K, Bassi C (2009) The Clavien–Dindo classification of surgical complications: five-year experience. Ann Surg 250(2):187–196CrossRef Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibañes E, Pekolj J, Slankamenac K, Bassi C (2009) The Clavien–Dindo classification of surgical complications: five-year experience. Ann Surg 250(2):187–196CrossRef
11.
Zurück zum Zitat Shapiro J, Van Lanschot JJB, Hulshof MC, van Hagen P, van Berge Henegouwen MI, Wijnhoven BP, van Laarhoven HW, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ (2015) Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 16(9):1090–1098CrossRefPubMed Shapiro J, Van Lanschot JJB, Hulshof MC, van Hagen P, van Berge Henegouwen MI, Wijnhoven BP, van Laarhoven HW, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ (2015) Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 16(9):1090–1098CrossRefPubMed
12.
Zurück zum Zitat Klevebro F, Alexandersson von Döbeln G, Wang N, Johnsen G, Jacobsen A-B, Friesland S, Hatlevoll I, Glenjen N, Lind P, Tsai J (2016) A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol 27(4):660–667CrossRefPubMed Klevebro F, Alexandersson von Döbeln G, Wang N, Johnsen G, Jacobsen A-B, Friesland S, Hatlevoll I, Glenjen N, Lind P, Tsai J (2016) A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol 27(4):660–667CrossRefPubMed
13.
Zurück zum Zitat Pasini F, de Manzoni G, Zanoni A, Grandinetti A, Capirci C, Pavarana M, Tomezzoli A, Rubello D, Cordiano C (2013) Neoadjuvant therapy with weekly docetaxel and cisplatin, 5-fluorouracil continuous infusion, and concurrent radiotherapy in patients with locally advanced esophageal cancer produced a high percentage of long-lasting pathological complete response. Cancer 119(5):939–945CrossRefPubMed Pasini F, de Manzoni G, Zanoni A, Grandinetti A, Capirci C, Pavarana M, Tomezzoli A, Rubello D, Cordiano C (2013) Neoadjuvant therapy with weekly docetaxel and cisplatin, 5-fluorouracil continuous infusion, and concurrent radiotherapy in patients with locally advanced esophageal cancer produced a high percentage of long-lasting pathological complete response. Cancer 119(5):939–945CrossRefPubMed
14.
Zurück zum Zitat Spigel DR, Greco FA, Meluch AA, Lane CM, Farley C, Gray JR, Clark BL, Burris HA III, Hainsworth JD (2010) Phase I/II trial of preoperative oxaliplatin, docetaxel, and capecitabine with concurrent radiation therapy in localized carcinoma of the esophagus or gastroesophageal junction. J Clin Oncol 28(13):2213–2219CrossRefPubMed Spigel DR, Greco FA, Meluch AA, Lane CM, Farley C, Gray JR, Clark BL, Burris HA III, Hainsworth JD (2010) Phase I/II trial of preoperative oxaliplatin, docetaxel, and capecitabine with concurrent radiation therapy in localized carcinoma of the esophagus or gastroesophageal junction. J Clin Oncol 28(13):2213–2219CrossRefPubMed
15.
Zurück zum Zitat Meredith KL, Weber JM, Turaga KK, Siegel EM, McLoughlin J, Hoffe S, Marcovalerio M, Shah N, Kelley S, Karl R (2010) Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer. Ann Surg Oncol 17(4):1159–1167CrossRefPubMed Meredith KL, Weber JM, Turaga KK, Siegel EM, McLoughlin J, Hoffe S, Marcovalerio M, Shah N, Kelley S, Karl R (2010) Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer. Ann Surg Oncol 17(4):1159–1167CrossRefPubMed
16.
Zurück zum Zitat Donahue JM, Nichols FC, Li Z, Schomas DA, Allen MS, Cassivi SD, Jatoi A, Miller RC, Wigle DA, Shen KR (2009) Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg 87(2):392–399CrossRefPubMedPubMedCentral Donahue JM, Nichols FC, Li Z, Schomas DA, Allen MS, Cassivi SD, Jatoi A, Miller RC, Wigle DA, Shen KR (2009) Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg 87(2):392–399CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Tsang J, Tong D, Lam K, Law B, Wong I, Chan D, Chan F, Kwong D, Law S (2017) Appropriate timing for surgery after neoadjuvant chemoradiation for esophageal cancer. Dis Esophagus 30(9):1–8CrossRefPubMed Tsang J, Tong D, Lam K, Law B, Wong I, Chan D, Chan F, Kwong D, Law S (2017) Appropriate timing for surgery after neoadjuvant chemoradiation for esophageal cancer. Dis Esophagus 30(9):1–8CrossRefPubMed
18.
Zurück zum Zitat van der Werf L, Dikken J, van der Willik E, van Berge Henegouwen M, Nieuwenhuijzen G, Wijnhoven B, Bosscha K, van Grieken N, Hartgrink H, van Hillegersberg R (2018) Time interval between neoadjuvant chemoradiotherapy and surgery for oesophageal or junctional cancer: a nationwide study. Eur J Cancer 91:76–85CrossRefPubMed van der Werf L, Dikken J, van der Willik E, van Berge Henegouwen M, Nieuwenhuijzen G, Wijnhoven B, Bosscha K, van Grieken N, Hartgrink H, van Hillegersberg R (2018) Time interval between neoadjuvant chemoradiotherapy and surgery for oesophageal or junctional cancer: a nationwide study. Eur J Cancer 91:76–85CrossRefPubMed
19.
Zurück zum Zitat Shapiro J, van Hagen P, Lingsma HF, Wijnhoven BP, Biermann K, ten Kate FJ, Steyerberg EW, van der Gaast A, van Lanschot JJB, Group CS (2014) Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer. Ann Surg 260(5):807–814CrossRefPubMed Shapiro J, van Hagen P, Lingsma HF, Wijnhoven BP, Biermann K, ten Kate FJ, Steyerberg EW, van der Gaast A, van Lanschot JJB, Group CS (2014) Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer. Ann Surg 260(5):807–814CrossRefPubMed
20.
Zurück zum Zitat Shaikh T, Ruth K, Scott WJ, Burtness BA, Cohen SJ, Konski AA, Cooper HS, Astsaturov I, Meyer JE (2015) Increased time from neoadjuvant chemoradiation to surgery is associated with higher pathologic complete response rates in esophageal cancer. Ann Thorac Surg 99(1):270–276CrossRefPubMed Shaikh T, Ruth K, Scott WJ, Burtness BA, Cohen SJ, Konski AA, Cooper HS, Astsaturov I, Meyer JE (2015) Increased time from neoadjuvant chemoradiation to surgery is associated with higher pathologic complete response rates in esophageal cancer. Ann Thorac Surg 99(1):270–276CrossRefPubMed
21.
Zurück zum Zitat Tessier W, Gronnier C, Messager M, Hec F, Mirabel X, Robb WB, Piessen G, Mariette C (2014) Does timing of surgical procedure after neoadjuvant chemoradiation affect outcomes in esophageal cancer? Ann Thorac Surg 97(4):1181–1189CrossRefPubMed Tessier W, Gronnier C, Messager M, Hec F, Mirabel X, Robb WB, Piessen G, Mariette C (2014) Does timing of surgical procedure after neoadjuvant chemoradiation affect outcomes in esophageal cancer? Ann Thorac Surg 97(4):1181–1189CrossRefPubMed
22.
Zurück zum Zitat Lin G, Han S-Y, Xu Y-P, Mao W-M (2017) Increasing the interval between neoadjuvant chemoradiotherapy and surgery in esophageal cancer: a meta-analysis of published studies. Dis Esophagus 30(7):1–8PubMed Lin G, Han S-Y, Xu Y-P, Mao W-M (2017) Increasing the interval between neoadjuvant chemoradiotherapy and surgery in esophageal cancer: a meta-analysis of published studies. Dis Esophagus 30(7):1–8PubMed
23.
Zurück zum Zitat Kataoka K, Takeuchi H, Mizusawa J, Igaki H, Ozawa S, Abe T, Nakamura K, Kato K, Ando N, Kitagawa Y (2017) Prognostic impact of postoperative morbidity after esophagectomy for esophageal cancer: exploratory analysis of JCOG9907. Ann Surg 265(6):1152–1157CrossRefPubMed Kataoka K, Takeuchi H, Mizusawa J, Igaki H, Ozawa S, Abe T, Nakamura K, Kato K, Ando N, Kitagawa Y (2017) Prognostic impact of postoperative morbidity after esophagectomy for esophageal cancer: exploratory analysis of JCOG9907. Ann Surg 265(6):1152–1157CrossRefPubMed
24.
Zurück zum Zitat Shridhar R, Takahashi C, Huston J, Doepker MP, Meredith KL (2018) Anastomotic leak and neoadjuvant chemoradiotherapy in esophageal cancer. J Gastrointest Oncol 9:894CrossRefPubMedPubMedCentral Shridhar R, Takahashi C, Huston J, Doepker MP, Meredith KL (2018) Anastomotic leak and neoadjuvant chemoradiotherapy in esophageal cancer. J Gastrointest Oncol 9:894CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R (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(7):1086CrossRefPubMedPubMedCentral Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R (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(7):1086CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Markar SR, Arya S, Karthikesalingam A, Hanna GB (2013) Technical factors that affect anastomotic integrity following esophagectomy: systematic review and meta-analysis. Ann Surg Oncol 20(13):4274–4281CrossRefPubMed Markar SR, Arya S, Karthikesalingam A, Hanna GB (2013) Technical factors that affect anastomotic integrity following esophagectomy: systematic review and meta-analysis. Ann Surg Oncol 20(13):4274–4281CrossRefPubMed
27.
Zurück zum Zitat Kassis ES, Kosinski AS, Ross P Jr, Koppes KE, Donahue JM, Daniel VC (2013) Predictors of anastomotic leak after esophagectomy: an analysis of the society of thoracic surgeons general thoracic database. Ann Thorac Surg 96(6):1919–1926CrossRefPubMed Kassis ES, Kosinski AS, Ross P Jr, Koppes KE, Donahue JM, Daniel VC (2013) Predictors of anastomotic leak after esophagectomy: an analysis of the society of thoracic surgeons general thoracic database. Ann Thorac Surg 96(6):1919–1926CrossRefPubMed
28.
Zurück zum Zitat Hironaka S, Tsubosa Y, Mizusawa J, Kii T, Kato K, Tsushima T, Chin K, Tomori A, Okuno T, Taniki T (2014) Phase I/II trial of 2-weekly docetaxel combined with cisplatin plus fluorouracil in metastatic esophageal cancer (JCOG 0807). Cancer Sci 105(9):1189–1195CrossRefPubMedPubMedCentral Hironaka S, Tsubosa Y, Mizusawa J, Kii T, Kato K, Tsushima T, Chin K, Tomori A, Okuno T, Taniki T (2014) Phase I/II trial of 2-weekly docetaxel combined with cisplatin plus fluorouracil in metastatic esophageal cancer (JCOG 0807). Cancer Sci 105(9):1189–1195CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Natsugoe S, Okumura H, Matsumoto M, Uchikado Y, Setoyama T, Yokomakura N, Ishigami S, Owaki T, Aikou T (2006) Randomized controlled study on preoperative chemoradiotherapy followed by surgery versus surgery alone for esophageal squamous cell cancer in a single institution. Dis Esophagus 19(6):468–472CrossRefPubMed Natsugoe S, Okumura H, Matsumoto M, Uchikado Y, Setoyama T, Yokomakura N, Ishigami S, Owaki T, Aikou T (2006) Randomized controlled study on preoperative chemoradiotherapy followed by surgery versus surgery alone for esophageal squamous cell cancer in a single institution. Dis Esophagus 19(6):468–472CrossRefPubMed
Metadaten
Titel
Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for locally advanced esophageal squamous cell carcinoma
verfasst von
Ken Sasaki
Yasuto Uchikado
Itaru Omoto
Takaaki Arigami
Yusaku Osako
Masahiro Noda
Hiroshi Okumura
Kosei Maemura
Ryutaro Higashi
Takashi Yoshiura
Shoji Natsugoe
Publikationsdatum
08.01.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 3/2019
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-018-03764-4

Weitere Artikel der Ausgabe 3/2019

Cancer Chemotherapy and Pharmacology 3/2019 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.