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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • German Rectal Cancer Study Group - (Autor:in)


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.


Seiten (von - bis)3212-3222
FachzeitschriftJournal of Clinical Oncology
PublikationsstatusVeröffentlicht - 1 Dez. 2019

Externe IDs

Scopus 85071830849
ORCID /0000-0002-9321-9911/work/142251968


Ziele für nachhaltige Entwicklung


  • Adenocarcinoma/mortality, Aged, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Chemoradiotherapy, Adjuvant/adverse effects, Consolidation Chemotherapy/adverse effects, Drug Administration Schedule, Female, Germany, Humans, Induction Chemotherapy/adverse effects, Male, Middle Aged, Neoadjuvant Therapy/adverse effects, Neoplasm Staging, Radiation Dosage, Rectal Neoplasms/mortality, Time Factors, Treatment Outcome