Randomized Phase II Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: CAO/ARO/AIO-12
| Autor: | Claus Rödel, Anke Schlenska-Lange, Tim Friede, Anca-Ligia Grosu, Emmanouil Fokas, Rainer Fietkau, Michael Flentje, Wolff Schmiegel, Michael Allgäuer, Wolf O. Bechstein, Thomas Brunner, Gunther Klautke, Matthias Schwarzbach, Gerhard G. Grabenbauer, G. Folprecht, Jürgen Weitz, Bülent Polat, Ludger Staib, Thomas Kuhnt, Ralf-Dieter Hofheinz, L. Jacobasch, Vittorio Paolucci, Christoph-Thomas Germer, Michael Ghadimi, Robert Grützmann |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
Cancer Research Chemotherapy medicine.medical_specialty business.industry Colorectal cancer medicine.medical_treatment Locally advanced Consolidation Chemotherapy medicine.disease 3. Good health law.invention Clinical trial 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law 030220 oncology & carcinogenesis Internal medicine Medicine 030211 gastroenterology & hepatology business Neoadjuvant therapy Chemoradiotherapy |
| Zdroj: | Journal of Clinical Oncology. 37:3212-3222 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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