Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study - Université de Picardie Jules Verne Accéder directement au contenu
Article Dans Une Revue Lancet Oncology Année : 2020

Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study

1 IGR - Institut Gustave Roussy
2 Département de chirurgie viscérale [Gustave Roussy]
3 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
4 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
5 ICM - Institut du Cancer de Montpellier
6 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
7 UNICANCER/CAL - Centre de Lutte contre le Cancer Antoine Lacassagne [Nice]
8 Centre Paul Papin(Angers)
9 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
10 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
11 Service de chirurgie digestive [CHU Rouen]
12 Service de Chirurgie Générale, Digestive et Endocrine [CHU Reims]
13 GEPA - Génétique Expérimentale en Productions Animales
14 UNICANCER/ICL - Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy]
15 CHU - Centre Hospitalier Universitaire [Grenoble]
16 Hôpital de Hautepierre [Strasbourg]
17 Centre Léon Bérard [Lyon]
18 Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon)
19 Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges]
20 Institut Curie [Paris]
21 Service de Chirurgie Digestive [CHRU Besançon]
22 CHU Tenon [AP-HP]
23 TIMONE - Hôpital de la Timone [CHU - APHM]
24 CHU Amiens-Picardie
25 SSPC - Simplification des soins chez les patients complexes - UR UPJV 7518
26 Embedded Computing Laboratory [Gif-sur-Yvette]
27 SBE - Service de biostatistique et d'épidémiologie
Amandine Pinto
  • Fonction : Auteur
Valeria Loi
  • Fonction : Auteur

Résumé

Background Diagnosis and treatment of colorectal peritoneal metastases at an early stage, before the onset of signs, could improve patient survival. We aimed to compare the survival benefit of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC), with surveillance, in patients at high risk of developing colorectal peritoneal metastases. Methods We did an open-label, randomised, phase 3 study in 23 hospitals in France. Eligible patients were aged 18-70 years and had a primary colorectal cancer with synchronous and localised colorectal peritoneal metastases removed during tumour resection, resected ovarian metastases, or a perforated tumour. Patients were randomly assigned (1:1) to surveillance or second-look surgery plus oxaliplatin-HIPEC (oxaliplatin 460 mg/m(2), or oxaliplatin 300 mg/m(2) plus irinotecan 200 mg/m(2), plus intravenous fluorouracil 400 mg/m(2)), or mitomycin-HIPEC (mitomycin 35 mg/m(2)) alone in case of neuropathy, after 6 months of adjuvant systemic chemotherapy with no signs of disease recurrence. Randomisation was done via a web-based system, with stratification by treatment centre, nodal status, and risk factors for colorectal peritoneal metastases. Second-look surgery consisted of a complete exploration of the abdominal cavity via xyphopubic incision, and resection of all peritoneal implants if resectable. Surveillance after resection of colorectal cancer was done according to the French Guidelines. The primary outcome was 3-year disease free survival, defined as the time from randomisation to peritoneal or distant disease recurrence, or death from any cause, whichever occurred first, analysed by intention to treat. Surgical complications were assessed in the second look surgery group only. This study was registered at ClinicalTrials.gov, NCT01226394. Findings Between June 11, 2010, and March 31, 2015, 150 patients were recruited and randomly assigned to a treatment group (75 per group). After a median follow-up of 50.8 months (IQR 47.0-54.8), 3-year disease-free survival was 53% (95% CI 41-64) in the surveillance group versus 44% (33-56) in the second-look surgery group (hazard ratio 0.97, 95% CI 0.61-1.56). No treatment-related deaths were reported. 29 (41%) of 71 patients in the second-look surgery group had grade 3-4 complications. The most common grade 3-4 complications were intra-abdominal adverse events (haemorrhage, digestive leakage) in 12 (23%) of 71 patients and haematological adverse events in 13 (18%) of 71 patients. Interpretation Systematic second-look surgery plus oxaliplatin-HIPEC did not improve disease-free survival compared with standard surveillance. Currently, essential surveillance of patients at high risk of developing colorectal peritoneal metastases appears to be adequate and effective in terms of survival outcomes. Copryright (C) 2020 Elsevier Ltd. All rights reserved.

Dates et versions

hal-03597470 , version 1 (04-03-2022)

Identifiants

Citer

Diane Goere, Olivier Glehen, Francois Quenet, Jean-Marc Guilloit, Jean-Marc Bereder, et al.. Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study. Lancet Oncology, 2020, 21 (9), pp.1147-1154. ⟨10.1016/S1470-2045(20)30322-3⟩. ⟨hal-03597470⟩
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