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Preoperative Oxaliplatin, Capecitabine, and External Beam Radiotherapy in Patients with Newly Diagnosed, Primary Operable, cT3NxM0, Low Rectal Cancer

A Phase II Study

Präoperative kombinierte Radiochemotherapie mit Oxaliplatin und Capecitabin beim lokal fortgeschrittenen, primär operablen, cT3NxM0, tiefen Rektumkarzinom – eine Phase-II-Studie

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Abstract

Purpose:

In patients with locally advanced rectal cancer (LARC), preoperative chemoradiation is known to improve local control, and down-staging of the tumor serves as a surrogate for survival. Intensification of the systemic therapy may lead to higher downstaging rates and, thus, enhance survival. This phase II study investigated the efficacy and safety of preoperative capecitabine and oxaliplatin in combination with radiotherapy.

Patients and Methods:

Patients with LARC of the mid and lower rectum, T3NxM0 staged by MRI received radiotherapy (total dose 45 Gy) in combination with oral capecitabine (825 mg/m2 twice a day on radiotherapy days; weeks 1–4) and oxaliplatin 50 mg/m2 intravenously (days 1, 8, 15, and 22). Efficacy was evaluated as rate of tumor down-categorization at the T level.

Results:

A total of 59 patients were enrolled (19 women, 40 men; median age of 61 years) and all were evaluable for efficacy and toxicity. Down-categorization at the T level was observed in 53% with pathological complete response in 6 patients (10%). Actual total radiotherapy, oxaliplatin and capecitabine doses received were 97%, 90%, and 93% of the protocol-specified preplanned doses, respectively. Grade 3/4 toxicity was observed in 15 patients (25%). The most frequent was diarrhea (12%).

Conclusions:

Preoperative chemoradiation with capecitabine and oxaliplatin is feasible in patients with MRI-proven cT3 LARC. The only clinically relevant toxicity was diarrhea. Overall, efficacy of the multimodality treatment was good, but not markedly exceeding that of 5-FU- or capecitabine-based chemoradiation approaches.

Zusammenfassung

Ziel:

Eine präoperative Radiochemotherapie verbessert bei Patienten mit einem tief sitzenden Rektumkarzinom (LARC) die lokale Tumorkontrolle und ein so genanntes „down-staging“ dient als Überlebenssurrogatparameter. Von einer Dosisintensivierung der systemischen Therapie kann man sich höhere Down-Staging-Raten erwarten und damit das Überleben verbessern. Diese multizentrische Phase-II-Studie soll die Wirksamkeit und Toxizität einer neoadjuvanten durch Capecitabin und Oxaliplatin intensivierten Radiochemotherapie prüfen.

Patienten und Methodik:

Patienten mit einem LARC, das mittels MRI als cT3NxM0 klassifizierten wurde, erhielten eine Radiotherapie (45 Gy in konventioneller Fraktionierung) mit konkomitanter Gabe von Capecitabin (oral 2 x täglich 825 mg an den Bestrahlungstagen, Woche 1–4) und Oxaliplatin intravenös 50mg/m2 (an den Tagen 1, 8, 15 und 22). Die Rate an Tumor-Down- Categorization dient als Parameter der Wirksamkeit.

Ergebnisse:

59 Patienten (davon 68% männlich, mittleres Alter 61 Jahre) wurden in die Studie eingeschlossen. Eine Down- Categorization in der T-Kategorie wurde in 53% der Patienten beobachtet, wobei 6 Patienten (10%) eine komplette pathologische Remission zeigten. Die tatsächlich verabreichte Strahlendosis betrug 97%, die Capecitabindosis 93% und die Oxaliplatindosis 90% der im Protokoll festgelegten Gesamtdosis. Akute Nebenwirkungen CTC-Grad ≥3 (Common Toxicity Criteria) wurden in 15 Patienten (25%) registriert, wobei mit 12% eine Diarrhoe am häufigsten vorkam.

Schlussfolgerung:

Eine präoperative Radiochemotherapie mit Capecitabin und Oxaliplatin ist bei Patienten mit mittels MRI diagnostiziertem cT3 LARC gut durchführbar. Die einzige klinisch relevante Nebenwirkung war eine Diarrhoe. Allerdings übertrifft die Wirksamkeit nicht wesentlich die bisherigen Erkenntnisse von Studien mit kontinuierlicher 5-Fluorouracil- oder alleiniger Capecitabingabe.

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Authors and Affiliations

  1. Department of Surgery, Paracelsus Private Medical University, Salzburg, Austria

    Dietmar Öfner MD, MSc

  2. Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria

    Dietmar Öfner MD, MSc & Matthias Zitt

  3. Department of Radio-Oncology, Feldkirch Hospital, Feldkirch, Austria

    Alexander F. DeVries

  4. Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

    Renate Schaberl-Moser

  5. Third Medical Department, Private Medical Paracelsus University Salzburg, Salzburg, Austria

    Richard Greil

  6. Department of Surgery, Leoben-Eisenerz Hospital, Leoben, Austria

    Hans Rabl

  7. Department of Surgery, St. Veit Hospital, St. Veit/Glan, Austria

    Jörg Tschmelitsch

  8. Department of Therapeutic Radiotherapy and Oncology, Medical University of Graz, Graz, Austria

    Karin S. Kapp

  9. Department of Radiotherapy, Private Medical Paracelsus University Salzburg, Salzburg, Austria

    Gerd Fastner

  10. Department of Hematology and Oncology, Leoben-Eisenerz Hospital, Leoben, Austria

    Felix Keil

  11. Department of Internal Medicine I, Innsbruck Medical University, Innsbruck, Austria

    Wolfgang Eisterer

  12. Department of Radiotherapy, Innsbruck Medical University, Innsbruck, Austria

    Robert Jäger

  13. Department of Pathology, Feldkirch Hospital, Feldkirch, Austria

    Felix Offner

  14. Department of Surgery, Medical University of Vienna, Vienna, Austria

    Michael Gnant

  15. Department of Internal Medicine IV, Wels-Grieskirchen Hospital, Wels, Austria

    Josef Thaler

  16. Head Department of Surgery, Paracelsus Private Medical University Salzburg, Müllner Hauptstr. 48, 5020, Salzburg, Austria

    Dietmar Öfner MD, MSc

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  1. Dietmar Öfner MD, MSc
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Consortia

TAKO 05/ABCSG R-02 Trial Investigators

Corresponding author

Correspondence to Dietmar Öfner MD, MSc.

Additional information

*ClinicalTrials.gov number, NCT00297141; Parts of this manuscript were previous published as an abstract at ASCO 2007 (Vol 25, No 18S, 2007: 14527).

**The Investigators participating in the Tyrolean Oncology Working Group trial 05 (TAKO 05) and Austrian Breast and Colorectal Cancer Study Group trial R-02 (ABCSG R-02) are listed in the Appendix.

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Öfner, D., DeVries, A.F., Schaberl-Moser, R. et al. Preoperative Oxaliplatin, Capecitabine, and External Beam Radiotherapy in Patients with Newly Diagnosed, Primary Operable, cT3NxM0, Low Rectal Cancer. Strahlenther Onkol 187, 100–107 (2011). https://doi.org/10.1007/s00066-010-2182-6

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