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Simultaneous neoadjuvant radiochemotherapy with capecitabine and oxaliplatin for locally advanced rectal cancer

Treatment outcome outside clinical trials

Simultane neoadjuvante Radiochemotherapie mit Capecitabin und Oxaliplatin beim lokal fortgeschrittenen Rektumkarzinom

Therapieergebnisse außerhalb klinischer Studien

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Abstract

Background

Phase II trials of neoadjuvant treatment in UICC-TNM stage II and III rectal cancer with capecitabine and oxaliplatin demonstrated favourable rates on tumour regression with acceptable toxicity.

Patients and methods

Retrospective evaluation of 34 patients treated from 2005–2008 outside clinical trials (CTR) with neoadjuvant irradiation (45–50.4 Gy) and simultaneous capecitabine 825 mg/m2 b.i.d. on days 1–14 and 22–35 and oxaliplatin 50 mg/m2 on days 1, 8, 22 and 29 (CAPOX). Twenty-six (77%) patients received one or two courses of capecitabine 1,000 mg/m2 b.i.d. on days 1–14 and oxaliplatin 130 mg/m2 on day 1 (XELOX) prior to simultaneous chemoradiotherapy.

Results

UICC-TNM stage regression was observed in 60% (n = 20). Dworak’s regression grades 3 and 4 were achieved in 18.2% (n = 6) and 15.1% (n = 5) of the patients. Sphincter-preserving surgery was performed in 53% (n = 8) of patients with a tumour of the lower rectum. Within the mean observation of 24 months, none of the patients relapsed locally, 1 patient had progressive disease and 5 patients (15%) relapsed distantly. Toxicity of grade 3 and 4 was mainly diarrhoea 18% (n = 6) and perianal pain 9% (n = 3). Nevertheless, severe cardiac events (n = 2), severe electrolyte disturbances (n = 2), and syncopes (n = 2) were observed as well.

Conclusion

Treatment efficacy and common toxicity are similar to the reports of phase I/II trials. However, several severe adverse events were observed in our cohort study. The predisposing factors for these events have yet to be studied and may have implications for the selection of patients outside CTR.

Zusammenfassung

Hintergrund

Phase-II-Studien zur neoadjuvanten Therapie des Rektumkarzinoms (UICC-TNM-Stadium II und III) mit Capecitabin und Oxaliplatin zeigten eine günstige Tumorregressionsrate bei akzeptabler Toxizität.

Patienten und Methoden

Retrospektive Auswertung der Daten von 34 Patienten (Nachsorge Tab. 1, Patientencharakteristika Tab. 2), die in den Jahren 2005–2008 außerhalb klinischer Studien eine neoadjuvante Strahlentherapie (45–50,4 Gy) simultan mit Capecitabin 825 mg/m2 2-mal täglich an den Tagen 1–14 und 22–35 und Oxaliplatin 50 mg/m2 an den Tagen 1, 8, 22 und 29 (CAPOX) erhielten. 26 (77%) Patienten bekamen 1–2 Zyklen Capecitabin 1000 mg/m2 2-mal täglich an den Tagen 1–14 und Oxaliplatin 130 mg/m2 am Tag 1 (XELOX) vor der simultanen Chemoradiotherapie.

Ergebnisse

Eine Regression des UICC-TNM-Stadiums wurde bei 60% (n = 20) beobachtet (Tab. 3). Regressionsgrade 3 und 4 nach Dworak wurden in 18,2% (n = 6) und 15,1% (n = 5) der Patienten erreicht (Tab. 4). Eine sphinktererhaltende Operation wurde in 53% (n = 8) der Patienten mit einem distalen Tumor realisiert. Innerhalb der Beobachtungszeit von 24 Monaten erlitt keiner der Patienten einen lokalen Rückfall. Eine Patientin zeigte eine kontinuierliche Tumorprogression und 5 Patienten (15%) entwickelten Fernmetastasen im Verlauf. Toxizität (Tab. 5) vom Grad (G) 3/4 manifestierte sich überwiegend als Diarrhoe 18% (n = 6) und perianaler Schmerz 9% (n = 3). Es traten jedoch 2 schwerwiegende kardiale Ereignisse, 2 Fälle von schwerer Elektrolytentgleisung und 2 Synkopen auf.

Schlussfolgerung

Die Effektivität und die allgemeine Toxizität in unserem Patientengut sind den Ergebnissen aus den Phase-I/II-Studien ähnlich. Es traten jedoch einzelne schwerwiegende Nebenwirkungen in unserer Kohorte auf. Die hierzu beitragenden Faktoren bedürfen einer weiteren Beobachtung und können Konsequenzen für die künftige Patientenselektion haben.

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Conflict of interest

The corresponding author states that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland

    J. Winkler, L. Zipp &  F. Zimmermann

  2. Outpatient Oncology Centre, Lörrach, Germany

    J. Knoblich

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  1. J. Winkler
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  2. L. Zipp
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  3. J. Knoblich
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  4. F. Zimmermann
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Correspondence to F. Zimmermann.

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Winkler, J., Zipp, L., Knoblich, J. et al. Simultaneous neoadjuvant radiochemotherapy with capecitabine and oxaliplatin for locally advanced rectal cancer. Strahlenther Onkol 188, 377–382 (2012). https://doi.org/10.1007/s00066-012-0073-8

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  • DOI: https://doi.org/10.1007/s00066-012-0073-8

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