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Cisplatin- vs. oxaliplatin-based radiosensitizing chemotherapy for squamous cell carcinoma of the esophagus

A comparison of two preoperative radiochemotherapy regimens

Cisplatin- vs. oxaliplatinbasierte Radiosensitizer-Chemotherapie beim Ösophagusplattenepithelkarzinom

Ein Vergleich zweier präoperativer Radiochemotherapieregime

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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.

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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.

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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

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