Abstract
Purpose
We aimed to present the clinical outcomes of adjuvant concurrent chemoradiotherapy (CCRT) with low-dose daily cisplatin regimen compared to the conventional 5-fluorouracil (5-FU)-based regimen for extrahepatic bile duct cancer (EHBDC).
Methods
From October 1994 to April 2013, 41 patients received adjuvant CCRT with low-dose daily regimen or 5-FU-based regimens. Nineteen patients received low-dose of cisplatin just before every delivery of radiation therapy, and 21 patients received two cycles of 5-FU-based regimen during radiotherapy. We compared the clinical outcomes between two adjuvant CCRT regimens.
Results
Adjuvant CCRT with low-dose daily cisplatin showed comparable toxicity profiles compared with that of a 5-FU-based regimen. The median follow-up time was 33 months (range, 5–205), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 34.2, 50.8, and 49.7%, respectively. Univariable analyses showed no significant differences in OS, LRRFS, and DMFS between the groups with two regimens. In multivariable analyses, chemotherapeutic regimen was a significant prognostic factor for OS, favoring the low-dose daily cisplatin regimen (HR = 2.491, p = 0.036) over 5-FU-based regimen, though not for LRRFS (p = 0.642) and DMFS (p = 0.756).
Conclusions
Adjuvant CCRT with low-dose daily cisplatin regimen showed acceptable toxicities and survivals compared to those of the 5-FU-based regimen. Low-dose daily cisplatin can be one of the feasible regimens for adjuvant CCRT for EHBDC.
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References
Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD (2005) Cholangiocarcinoma. Lancet 366(9493):1303–1314. doi:10.1016/S0140-6736(05)67530-7
Jarnagin WR, Ruo L, Little SA, Klimstra D, D’Angelica M, DeMatteo RP, Wagman R, Blumgart LH, Fong Y (2003) Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies. Cancer 98(8):1689–1700. doi:10.1002/cncr.11699
Jang JY, Kim SW, Park DJ, Ahn YJ, Yoon YS, Choi MG, Suh KS, Lee KU, Park YH (2005) Actual long-term outcome of extrahepatic bile duct cancer after surgical resection. Ann Surg 241(1):77–84. doi:10.1097/01.sla.0000150166.94732.88
Koo TR, Eom KY, Kim IA, Cho JY, Yoon YS, Hwang DW, Han HS, Kim JS (2014) Patterns of failure and prognostic factors in resected extrahepatic bile duct cancer: implication for adjuvant radiotherapy. Radiat Oncol J 32(2):63–69. doi:10.3857/roj.2014.32.2.63
Borghero Y, Crane CH, Szklaruk J, Oyarzo M, Curley S, Pisters PW, Evans D, Abdalla EK, Thomas MB, Das P, Wistuba II, Krishnan S, Vauthey JN (2008) Extrahepatic bile duct adenocarcinoma: patients at high-risk for local recurrence treated with surgery and adjuvant chemoradiation have an equivalent overall survival to patients with standard-risk treated with surgery alone. Ann Surg Oncol 15(11):3147–3156. doi:10.1245/s10434-008-9998-7
Nelson JW, Ghafoori AP, Willett CG, Tyler DS, Pappas TN, Clary BM, Hurwitz HI, Bendell JC, Morse MA, Clough RW, Czito BG (2009) Concurrent chemoradiotherapy in resected extrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys 73(1):148–153. doi:10.1016/j.ijrobp.2008.07.008
Kim TH, Han SS, Park SJ, Lee WJ, Woo SM, Moon SH, Yoo T, Kim SS, Kim SH, Hong EK, Kim DY, Park JW (2011) Role of adjuvant chemoradiotherapy for resected extrahepatic biliary tract cancer. Int J Radiat Oncol Biol Phys 81(5):e853–e859. doi:10.1016/j.ijrobp.2010.12.019
Park JH, Choi EK, Ahn SD, Lee SW, Song SY, Yoon SM, Kim YS, Lee YS, Lee SG, Hwang S, Lee YJ, Park KM, Kim TW, Chang HM, Lee JL, Kim JH (2011) Postoperative chemoradiotherapy for extrahepatic bile duct cancer. Int J Radiat Oncol Biol Phys 79(3):696–704. doi:10.1016/j.ijrobp.2009.12.031
Kim K, Chie EK, Jang JY, Kim SW, Han SW, Oh DY, Im SA, Kim TY, Bang YJ, Ha SW (2012) Adjuvant chemoradiotherapy after curative resection for extrahepatic bile duct cancer: a long-term single center experience. Am J Clin Oncol 35(2):136–140. doi:10.1097/COC.0b013e318209aa29
Ushijima K, Fujiyoshi K, Kawano K, Tsuda N, Nishio S, Eto H, Kamura T (2013) Concurrent chemoradiotherapy with low-dose daily cisplatin for high risk uterine cervical cancer: a long-term follow-up study. J Gynecol Oncol 24(2):108–113. doi:10.3802/jgo.2013.24.2.108
Jeremic B, Shibamoto Y, Milicic B, Nikolic N, Dagovic A, Aleksandrovic J, Vaskovic Z, Tadic L (2000) Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18(7):1458–1464
Uitterhoeve AL, Belderbos JS, Koolen MG, van der Vaart PJ, Rodrigus PT, Benraadt J, Koning CC, Gonzalez DG, Bartelink H (2000) Toxicity of high-dose radiotherapy combined with daily cisplatin in non-small cell lung cancer: results of the EORTC 08912 phase I/II study. Eur J Cancer 36(5):592–600. doi:10.1016/S0959-8049(99)00315-9
Kawakami H, Uno T, Isobe K, Ueno N, Aruga T, Sudo K, Yamaguchi T, Saisho H, Kawata T, Ito H (2005) Toxicities and effects of involved-field irradiation with concurrent cisplatin for unresectable carcinoma of the pancreas. Int J Radiat Oncol Biol Phys 62(5):1357–1362. doi:10.1016/j.ijrobp.2004.12.041
Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA (2004) New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol 57(12):1288–1294. doi:10.1016/j.jclinepi.2004.03.012
R Development Core Team (2016) R: A language and environment for the statistical computing, R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/
Im JH, Seong J, Lee IJ, Park JS, Yoon DS, Kim KS, Lee WJ, Park KR (2016) Surgery alone versus surgery followed by chemotherapy and radiotherapy in resected extrahepatic bile duct cancer: treatment outcome analysis of 336 patients. Cancer Res Treat 48(2):583–595. doi:10.4143/crt.2015.091
Hoehn RS, Wima K, Ertel AE, Meier A, Ahmad SA, Shah SA, Abbott DE (2015) Adjuvant chemotherapy and radiation therapy is associated with improved survival for patients with extrahepatic cholangiocarcinoma. Ann Surg Oncol 22(Suppl 3):S1133–S1139. doi:10.1245/s10434-015-4599-8
Hanawa S, Mitsuhashi A, Usui H, Yamamoto N, Watanabe-Nemoto M, Nishikimi K, Uehara T, Tate S, Uno T, Shozu M (2015) Daily low-dose Cisplatin-based concurrent chemoradiotherapy for the treatment of cervical cancer in patients 70 years or older. Int J Gynecol Cancer 25(5):891–896. doi:10.1097/IGC.0000000000000436
Lim KH, Oh DY, Chie EK, Jang JY, Im SA, Kim TY, Kim SW, Ha SW, Bang YJ (2009) Adjuvant concurrent chemoradiation therapy (CCRT) alone versus CCRT followed by adjuvant chemotherapy: which is better in patients with radically resected extrahepatic biliary tract cancer?: a non-randomized, single center study. BMC Cancer 9:345. doi:10.1186/1471-2407-9-345
Acknowledgements
This work was supported by the new faculty research fund of Ajou University School of Medicine. The authors thank Stephen Kim for assistance with manuscript editing.
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Kim, SW., Noh, O.K., Kim, J.H. et al. Adjuvant concurrent chemoradiotherapy with low-dose daily cisplatin for extrahepatic bile duct cancer. Cancer Chemother Pharmacol 79, 1161–1167 (2017). https://doi.org/10.1007/s00280-017-3312-y
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DOI: https://doi.org/10.1007/s00280-017-3312-y