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Published in: Radiation Oncology 1/2018

Open Access 01-12-2018 | Research

Comparison of definite chemoradiation therapy with carboplatin/paclitaxel or cisplatin/5-fluoruracil in patients with squamous cell carcinoma of the esophagus

Authors: Stefan Münch, Steffi U. Pigorsch, Michal Devečka, Hendrik Dapper, Wilko Weichert, Helmut Friess, Rickmer Braren, Stephanie E. Combs, Daniel Habermehl

Published in: Radiation Oncology | Issue 1/2018

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Abstract

Background

While neoadjuvant chemoradiation therapy (nCRT) with subsequent surgery is the treatment of choice for patients with locally advanced or node-positive squamous cell carcinoma of the esophagus (SCC) suitable for surgery, patients who are unsuitable for surgery or who refuse surgery should be treated with definite chemoradiation therapy (dCRT). Purpose of this study was to compare toxicity and oncologic outcome of dCRT with either cisplatin and 5-fluoruracil (CDDP/5FU) or carboplatin and paclitaxel (Carb/TAX) in patients with SCC.

Methods

Twenty-two patients who received dCRT with carboplatin (AUC2, weekly) and paclitaxel (50 mg per square meter of body-surface area, weekly) were retrospectively compared to 25 patients who were scheduled for dCRT with cisplatin (20 mg/m2/d) and 5-fluoruracil (500 mg/m2/d) on day 1–5 and day 29–33. For the per-protocol (PP) analysis, PP treatment was defined as complete radiation therapy with at least 54Gy and at least three complete cycles of Carb/TAX or complete radiation therapy with at least 54Gy and at least one complete cycle of CDDP/5FU. While patients who were scheduled for dCRT with Carb/TAX received a significantly higher total radiation dose (median dose 59.4Gy vs. 54Gy, p < 0.001) than patients who were scheduled for dCRT with CDDP/5FU, no significant differences were seen for other parameters (age, sex, TNM-stage, grading and tumor extension).

Results

Forty-seven patients (25 patients treated with CDDP/5FU and 22 patients treated with Carb/TAX) were evaluated for the intention-to-treat (ITT) analysis and 41 of 47 patients (23 patients treated with CDDP/5FU and 18 patients treated with Carb/TAX) were evaluated for the PP analysis. Severe myelotoxicity (≥ III°) was seen in 52% (CDDP/5FU) and 55% of patients (Carb/TAX), respectively (p = 1.000). In the univariate binary logistic regression analysis, patients age was the only factor associated with an increased risk of ≥ III° myelotoxicity (hazard ratio 1.145, 95% CI 1.035; 1.266; p = 0.009). Regarding treatment efficiency, no significant differences were seen for overall survival (OS) and freedom from relapse (FFR) between both treatment groups.

Conclusion

Myelotoxicity and oncologic outcome under dCRT were not different for patients with SCC of the esophagus treated with either CDDP/5FU or Carb/TAX. The putative equivalence of dCRT with Carb/TAX in this setting should be further investigated in prospective trials. However, our data reveal that the risk of significant myelotoxicity increases with patient age and therefore other chemotherapy regimens might be evaluated in elderly patients.
Literature
1.
go back to reference Howlader N N.A. Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2014, based on November 2016 SEER data submission, posted to the SEER web site,Bethesda, MD, National Cancer Institute 2017https://seer.cancer.gov/csr/1975_2014/ . Howlader N N.A. Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2014, based on November 2016 SEER data submission, posted to the SEER web site,Bethesda, MD, National Cancer Institute 2017https://​seer.​cancer.​gov/​csr/​1975_​2014/​ .
2.
go back to reference Ferlay JSI, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase no. 11. International Agency for Research on Cancer: Lyon; 2013. Available from: http://globocan.iarc.fr. Ferlay JSI, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase no. 11. International Agency for Research on Cancer: Lyon; 2013. Available from: http://​globocan.​iarc.​fr.
3.
4.
go back to reference Porschen R, et al. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus (Langversion 1.0 - September 2015, AWMF-Registernummer: 021/023OL). Z Gastroenterol. 2015;53(11):1288–347. Z Gastroenterol, 2015 53(11): p. 1288–347CrossRefPubMed Porschen R, et al. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus (Langversion 1.0 - September 2015, AWMF-Registernummer: 021/023OL). Z Gastroenterol. 2015;53(11):1288–347. Z Gastroenterol, 2015 53(11): p. 1288–347CrossRefPubMed
5.
go back to reference van Hagen P, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84.CrossRefPubMed van Hagen P, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84.CrossRefPubMed
6.
go back to reference Tepper J, et al. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008;26(7):1086–92.CrossRefPubMedPubMedCentral Tepper J, et al. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008;26(7):1086–92.CrossRefPubMedPubMedCentral
7.
go back to reference Kranzfelder M, et al. Meta-analysis of neoadjuvant treatment modalities and definitive non-surgical therapy for oesophageal squamous cell cancer. Br J Surg. 2011;98(6):768–83.CrossRefPubMed Kranzfelder M, et al. Meta-analysis of neoadjuvant treatment modalities and definitive non-surgical therapy for oesophageal squamous cell cancer. Br J Surg. 2011;98(6):768–83.CrossRefPubMed
9.
go back to reference Blom RL, et al. Comparison of two neoadjuvant chemoradiotherapy regimens in patients with potentially curable esophageal carcinoma. Dis Esophagus. 2014;27(4):380–7.CrossRefPubMed Blom RL, et al. Comparison of two neoadjuvant chemoradiotherapy regimens in patients with potentially curable esophageal carcinoma. Dis Esophagus. 2014;27(4):380–7.CrossRefPubMed
10.
go back to reference Munch S, et al. Comparison of neoadjuvant chemoradiation with carboplatin/ paclitaxel or cisplatin/ 5-fluoruracil in patients with squamous cell carcinoma of the esophagus. Radiat Oncol. 2017;12(1):182.CrossRefPubMedPubMedCentral Munch S, et al. Comparison of neoadjuvant chemoradiation with carboplatin/ paclitaxel or cisplatin/ 5-fluoruracil in patients with squamous cell carcinoma of the esophagus. Radiat Oncol. 2017;12(1):182.CrossRefPubMedPubMedCentral
11.
go back to reference Ruppert BN, et al. Cisplatin/Irinotecan versus carboplatin/paclitaxel as definitive chemoradiotherapy for locoregionally advanced esophageal cancer. Am J Clin Oncol. 2010;33(4):346–52.CrossRefPubMed Ruppert BN, et al. Cisplatin/Irinotecan versus carboplatin/paclitaxel as definitive chemoradiotherapy for locoregionally advanced esophageal cancer. Am J Clin Oncol. 2010;33(4):346–52.CrossRefPubMed
12.
go back to reference Haj Mohammad N, et al. Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma. BMC Cancer. 2014;14:56.CrossRefPubMedPubMedCentral Haj Mohammad N, et al. Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma. BMC Cancer. 2014;14:56.CrossRefPubMedPubMedCentral
13.
go back to reference Noronha V, et al. Clinical outcome in definitive concurrent Chemoradiation with weekly paclitaxel and carboplatin for locally advanced esophageal and Junctional Cancer. Oncol Res. 2016;23(4):183–95.CrossRefPubMed Noronha V, et al. Clinical outcome in definitive concurrent Chemoradiation with weekly paclitaxel and carboplatin for locally advanced esophageal and Junctional Cancer. Oncol Res. 2016;23(4):183–95.CrossRefPubMed
14.
go back to reference Honing J, et al. A comparison of carboplatin and paclitaxel with cisplatinum and 5-fluorouracil in definitive chemoradiation in esophageal cancer patients. Ann Oncol. 2014;25(3):638–43.CrossRefPubMedPubMedCentral Honing J, et al. A comparison of carboplatin and paclitaxel with cisplatinum and 5-fluorouracil in definitive chemoradiation in esophageal cancer patients. Ann Oncol. 2014;25(3):638–43.CrossRefPubMedPubMedCentral
15.
go back to reference Herskovic A, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992;326(24):1593–8.CrossRefPubMed Herskovic A, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992;326(24):1593–8.CrossRefPubMed
16.
go back to reference Cooper JS, et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01) Radiation Therapy Oncology Group. JAMA. 1999;281(17):1623–7.CrossRefPubMed Cooper JS, et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01) Radiation Therapy Oncology Group. JAMA. 1999;281(17):1623–7.CrossRefPubMed
17.
go back to reference Minsky BD, et al. INT 0123 (radiation therapy oncology group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002;20(5):1167–74.CrossRefPubMed Minsky BD, et al. INT 0123 (radiation therapy oncology group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002;20(5):1167–74.CrossRefPubMed
18.
go back to reference Kim HJ, et al. Dose-response relationship between radiation dose and loco-regional control in patients with stage II-III esophageal Cancer treated with definitive Chemoradiotherapy. Cancer Res Treat. 2017;49(3):669–77.CrossRefPubMed Kim HJ, et al. Dose-response relationship between radiation dose and loco-regional control in patients with stage II-III esophageal Cancer treated with definitive Chemoradiotherapy. Cancer Res Treat. 2017;49(3):669–77.CrossRefPubMed
19.
go back to reference Munch S, et al. Comparison of dosimetric parameters and toxicity in esophageal cancer patients undergoing 3D conformal radiotherapy or VMAT. Strahlenther Onkol. 2016;192(10):722–9.CrossRefPubMed Munch S, et al. Comparison of dosimetric parameters and toxicity in esophageal cancer patients undergoing 3D conformal radiotherapy or VMAT. Strahlenther Onkol. 2016;192(10):722–9.CrossRefPubMed
20.
go back to reference Haefner MF, et al. Intensity-modulated versus 3-dimensional conformal radiotherapy in the definitive treatment of esophageal cancer: comparison of outcomes and acute toxicity. Radiat Oncol. 2017;12(1):131.CrossRefPubMedPubMedCentral Haefner MF, et al. Intensity-modulated versus 3-dimensional conformal radiotherapy in the definitive treatment of esophageal cancer: comparison of outcomes and acute toxicity. Radiat Oncol. 2017;12(1):131.CrossRefPubMedPubMedCentral
Metadata
Title
Comparison of definite chemoradiation therapy with carboplatin/paclitaxel or cisplatin/5-fluoruracil in patients with squamous cell carcinoma of the esophagus
Authors
Stefan Münch
Steffi U. Pigorsch
Michal Devečka
Hendrik Dapper
Wilko Weichert
Helmut Friess
Rickmer Braren
Stephanie E. Combs
Daniel Habermehl
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2018
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-018-1085-z

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