Thématique :
- Cancers autres (hors CCR et CHC)
Originalité :
Solidité :
Doit faire évoluer notre pratique :
Pas encore
Nom du veilleur :
Professeur Thomas APARICIO
Coup de coeur :
Journal of clinical oncology (JCO)
  2019 May:JCO1900308.  
  doi: 10.1200/JCO.19.00308.  
  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; German Rectal Cancer Study Group.  



Total neoadjuvant therapy is a new paradigm for rectal cancer treatment. Optimal scheduling of preoperative chemoradiotherapy(CRT) and chemotherapy remains to be established.


We conducted a multicenter, randomizedphase 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.


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.


Up-front CRT followed by chemotherapy resulted in better compliance with CRT but worse compliance with chemotherapycompared with group A. Long-term follow-up will assess whether improved pCR in group B translates to better oncologic outcome.

Question posée
Quel traitement néo-adjuvant est associé au meilleur taux de réponse histologique complète : chimiothérapie puis radiochimiothérapie (groupe A) ou radiochimiothérapie puis chimiothérapie (groupe B) ?
Question posée
La radiochimiothérapie suivie de chimiothérapie a un taux de réponse complète de 25% (versus 17% dans le groupe A).

Cette étude peut apporter des éléments pour le choix de bras de traitements pour de futurs essais.