Randomized Phase II Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: CAO/ARO/AIO-12

Fokas E, Allgäuer M, Polat B, Klautke G, Grabenbauer GG, Fietkau R, Kuhnt T, Staib L, Brunner T, Grosu AL, Schmiegel W, Jacobasch L, Weitz J, Folprecht G, Schlenska-Lange A, Flentje M, Germer CT, Grützmann R, Schwarzbach M, Paolucci V, Bechstein WO, Friede T, Ghadimi M, Hofheinz RD, Rödel C (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Journal of Clinical Oncology American Society of Clinical Oncology

Book Volume: 37

Pages Range: 3212-3222

Journal Issue: 34

DOI: 10.1200/JCO.19.00308

Abstract

PURPOSE: Total neoadjuvant therapy is a new paradigm for rectal cancer treatment. Optimal scheduling of preoperative chemoradiotherapy (CRT) and chemotherapy remains to be established. PATIENTS AND METHODS: We conducted a multicenter, randomized, phase II trial using a pick-the-winner design on the basis of the hypothesis of an increased pathologic complete response (pCR) of 25% after total neoadjuvant therapy compared with standard 15% after preoperative CRT. Patients with stage II or III rectal cancer were assigned to group A for induction chemotherapy using three cycles of fluorouracil, leucovorin, and oxaliplatin before fluorouracil/oxaliplatin CRT (50.4 Gy) or to group B for consolidation chemotherapy after CRT. Secondary end points included toxicity, compliance, and surgical morbidity. RESULTS: Of the 311 patients enrolled, 306 patients were evaluable (156 in group A and 150 in group B). CRT-related grade 3 or 4 toxicity was lower (37% v 27%) and compliance with CRT higher in group B (91%, 78%, and 76% v 97%, 87%, and 93% received full-dose radiotherapy, concomitant fluorouracil, and concomitant oxaliplatin in groups A and B, respectively); 92% versus 85% completed all induction/consolidation chemotherapy cycles, respectively. The longer interval between completion of CRT and surgery in group B (median 90 v 45 days in group A) did not increase surgical morbidity. A pCR in the intention-to-treat population was achieved in 17% in group A and in 25% in group B. Thus, only group B (P < .001), but not group A (P = .210), fulfilled the predefined statistical hypothesis. CONCLUSION: Up-front CRT followed by chemotherapy resulted in better compliance with CRT but worse compliance with chemotherapy compared with group A. Long-term follow-up will assess whether improved pCR in group B translates to better oncologic outcome.

Authors with CRIS profile

Rainer Fietkau Lehrstuhl für Strahlentherapie Robert Grützmann Lehrstuhl für Allgemein- und Viszeralchirurgie

Involved external institutions

Goethe-Universität Frankfurt am Main DE Germany (DE) Universitätsklinikum Göttingen DE Germany (DE) Ruhr-Universität Bochum (RUB) DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Universitätsklinikum Mannheim DE Germany (DE) Universitätsklinikum Würzburg DE Germany (DE) Klinikum Frankfurt Höchst DE Germany (DE) Städtische Kliniken Esslingen DE Germany (DE) Universität Leipzig DE Germany (DE) Ketteler Krankenhaus DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Klinikum Coburg DE Germany (DE) Krankenhaus Barmherzige Brüder DE Germany (DE)

How to cite

APA:

Fokas, E., Allgäuer, M., Polat, B., Klautke, G., Grabenbauer, G.G., Fietkau, R.,... Rödel, C. (2019). Randomized Phase II Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: CAO/ARO/AIO-12. Journal of Clinical Oncology, 37(34), 3212-3222. https://doi.org/10.1200/JCO.19.00308

MLA:

Fokas, Emmanouil, et al. "Randomized Phase II Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: CAO/ARO/AIO-12." Journal of Clinical Oncology 37.34 (2019): 3212-3222.

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