Abstract
Purpose
To compare the outcomes of two neoadjuvant radiochemotherapy (N-RCT) regimens for squamous cell carcinoma of the esophagus (ESCC).
Methods
The standard N-RCT regimen for ESCC at our institution between 2002 and 2011 was a total dose of 45 Gy (1.8-Gy fractions) with concomitant cisplatin (20 mg/m2, days 1–5 and 29–33) and 5-fluorouracil (5-FU; 225 mg/m2, 24 h continuous infusion on days 1–33). During the same period, a phase I/II study comparing the standard ESCC N-RCT protocol with a regimen identical except for the replacement of cisplatin with weekly oxaliplatin (40–50 mg/m2) was performed at our center. The standard regimen was used to treat 40 patients; 37 received the oxaliplatin regimen. All patients subsequently underwent radical resection with reconstruction according to tumor location and two-field lymph node dissection.
Results
Median follow-up time from the start of N-RCT was 74 months (range 3–116 months). The two patient groups were comparable in terms of demographic and baseline tumor characteristics. R0 resection was achieved in 37/39 patients (95 %) in the cisplatin-based N-RCT group, compared to 24/37 (65 %) in the oxaliplatin-based group (p = 0.002). A pathological complete response (pCR) was seen in the resection specimens from 18/39 patients (46 %) in the cisplatin-based N-RCT group and in 8/37 (22 %) oxaliplatin-group patients. In the cisplatin group, 2- and 5-year overall survival (OS) rates were 67 ± 8 % and 60 ± 8 %, respectively (median OS 103 months), compared to 38 ± 8 % and 32 ± 8 %, respectively, for the oxaliplatin group (median OS 17 months; hazard ratio, HR 0.452; 95 % confidence interval, CI 0.244–0.839; p = 0.012).
Conclusion
Oxaliplatin-based N-RCT resulted in poorer outcomes in ESCC patients and should not routinely replace cisplatin-based N-RCT.
Zusammenfassung
Hintergrund
Unser Ziel war es, die Ergebnisse zweier neoadjuvanter Radiochemotherapie- (N-RCT-) Konzepte mit nachfolgender Resektion beim fortgeschrittenen Plattenepithelzellkarzinom des Ösophagus (ESCC) retrospektiv miteinander zu vergleichen.
Patienten und Methodik
Das Standardkonzept für eine N-RCT eines ESCC in unserer Klinik zwischen den Jahren 2002 und 2011 war eine Strahlentherapie mit 45 Gy in 1,8-Gy-Fraktionen mit gleichzeitiger Gabe von Cisplatin (20 mg/m2, Tage 1–5 und 29–33) und 5-Fluoruracil (5-FU, 225 mg/m2, 24 h kontinuierliche Infusion an den Tagen 1–33)
Im selben Zeitraum wurde an unserer Klinik eine Phase-I/II-Studie für N-RCT bei ESCC durchgeführt, in welcher ein Therapiekonzept benutzt wurde, das mit unserem Standardkonzept identisch war, bis auf den Unterschied, dass die Gabe von Cisplatin durch eine wöchentliche Gabe von Oxaliplatin ersetzt wurde (40–50 mg/m2). Mit unserem Standardkonzept wurden 40 Patienten behandelt, 37 mit dem Konzept der Phase-I/II-Studie. An allen Patienten wurde anschließend eine radikale Resektion des Ösophagus mit einer entsprechenden Rekonstruktion und einer 2-Felder-Lymphknotendissektion vollzogen.
Ergebnisse
Die mediane Nachbeobachtungszeit seit Beginn der N-RCT lag bei 74 Monaten (Spanne 3–116 Monate). Die beiden Patientengruppen waren bezüglich der demographischen und grundsätzlichen Tumoreigenschaften gut vergleichbar. Eine R0-Resektion konnte in der cisplatinbasierten Behandlungsgruppe bei 37/39 Patienten (95 %) erfolgen, verglichen mit 24/37 Patienten (65 %) in der oxaliplatinbasierten Gruppe (p = 0,002). Eine pathologische komplette Remission konnte bei 18 Patienten (46 %) der Cisplatin- und 8 Patienten (22 %) der Oxaliplatin-Gruppe erreicht werden.
Die 2- und 5-Jahres-Gesamtüberlebensraten (OS) betrugen 67 ± 8 % und 60 ± 8 % in der Cisplatin-Gruppe (medianes OS 103 Monate), verglichen mit 38 ± 8 % und 32 ± 8 % in der Oxaliplatin-Gruppe (medianes OS 17 Monate; HR 0,452; 95 %-KI 0,244–0,839; p = 0,012)
Schlussfolgerung
Eine N-RCT mit Oxaliplatin anstelle von Cisplatin führte zu schlechteren Ergebnissen bei den ESCC-Patienten und sollte die N-RCT mit Cisplatin nicht standardmäßig ersetzen.
Similar content being viewed by others
References
Van Hagen P, Hulshof MC, van Lanschot JJ et al (2012) Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366:2074–2084
Kranzfelder M, Schuster T, Geinitz H et al (2011) Meta-analysis of neoadjuvant treatment modalities and definitive non-surgical therapy for oesophageal squamous cell cancer. Br J Surg 98:768–783
Lordick F, Hölscher AH, Haustermans K et al (2013) Multimodal treatment of esophageal cancer. Langenbecks Arch Surg 398:177–187
Stahl M, Stuschke M, Lehmann N et al (2005) Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 23:2310–2317
Fakhrian K, Gamisch N, Schuster T et al (2012) Salvage radiotherapy in patients with recurrent esophageal carcinoma. Strahlenther Onkol 188:136–142
Lorenzen S, Brücher B, Zimmermann F et al (2008) Neoadjuvant continuous infusion of weekly 5-fluorouracil and escalating doses of oxaliplatin plus concurrent radiation in locally advanced oesophageal squamous cell carcinoma: results of a phase I/II trial. Br J Cancer 99:1020–1026
Sobin LH, Wittekind C (eds) (2002) UICC International Union Against Cancer. Esophagus (ICD-O C15). TMN classification of malignant tumors, 6th edn. Wiley-Liss, New York
Becker K, Mueller JD, Schulmacher C et al (1999) Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer 85:1484–1489
Woynarowski JM, Faivre S, Herzig M et al (2000) Oxaliplatin-induced damage of cellular DNA. Mol Pharmacol 58:920–927
Saris CP, Van de Vaart PJM, Rietbroek RC et al (1996) In vitro formation of DNA adducts by cisplatin, lobaplatin and oxaliplatin in calf thymus DNA in solution and in cultured human cells. Carcinogenesis17:2763–2769
Woynarowski JM, Chapman WG, Napier C et al (1998) Sequence- and region-specificity of oxaliplatin adducts in naked and cellular DNA. Mol Pharmacol 54:770–777
Winkler J1, Zipp L, Knoblich J, Zimmermann F (2012) Simultaneous neoadjuvant radiochemotherapy with capecitabine and oxaliplatin for locally advancedrectal cancer. Treatment outcome outside clinical trials. Strahlenther Onkol 188:377–382
Boda-Heggemann J, Weiss C, Schneider V et al (2013) Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer. Strahlenther Onkol 189:417–423
Hosein PJ, Macintyre J, Kawamura C et al (2012) A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer 12:199
Gao YH, Zhang X, An X et al (2014) Oxaliplatin and capecitabine concomitant with neoadjuvant radiotherapy and extended to the resting period in high risk locally advanced rectal cancer. Strahlenther Onkol 190:158–164
Conroy T, Yataghène Y, Etienne PL et al (2010) Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer. Br J Cancer 103:1349–1355
Conroy T, Galais MP, Raoul JL et al (2012) Phase III randomized trial of definitive chemoradiotherapy (CRT) with FOLFOX or cisplatin and fluorouracil in esophageal cancer (EC): final results of the PRODIGE 5/ACCORD 17 trial. J Clin Oncol 30(18) (ASCO Annual Meeting Abstracts. June 20 Supplement)
Montagnani F, Turrisi G, Marinozzi C et al (2011) Effectiveness and safety of oxaliplatin compared to cisplatin for advanced, unresectable gastric cancer: a systematic review and meta-analysis. Gastric Cancer14:50–55
Compliance with ethical guidelines
Conflict of interest
K. Fakhrian, A. D. Ordu, B. Haller, J. Theisen, F. Lordick, V. Bišof, M. Molls and H. Geinitz state that there are no conflicts of interest.
All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fakhrian, K., Ordu, A., Haller, B. et al. Cisplatin- vs. oxaliplatin-based radiosensitizing chemotherapy for squamous cell carcinoma of the esophagus. Strahlenther Onkol 190, 987–992 (2014). https://doi.org/10.1007/s00066-014-0661-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00066-014-0661-x