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.

Adolescent Adult Aged Colorectal Neoplasms / drug therapy Disease-Free Survival Female Fluorouracil / administration & dosage Humans Hyperthermia, Induced / methods Leucovorin / administration & dosage Male Middle Aged Neoplasm Metastasis Neoplasm Recurrence, Local / drug therapy Oxaliplatin / administration & dosage Peritoneal Neoplasms / drug therapy Risk Factors Second-Look Surgery / methods Young Adult

Journal

The Lancet. Oncology

ISSN: 1474-5488

Titre abrégé: Lancet Oncol

Pays: England

ID NLM: 100957246

Informations de publication

Date de publication:
09 2020

Historique:

received: 03 03 2020

revised: 06 05 2020

accepted: 11 05 2020

pubmed: 28 7 2020

medline: 24 9 2020

entrez: 28 7 2020

Statut: ppublish

Résumé

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. 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 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. 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. French National Cancer Institute.

Sections du résumé

BACKGROUND

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

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.

FUNDING

French National Cancer Institute.

Identifiants

DOI: 10.1016/S1470-2045(20)30322-3 PMID: 32717180

pubmed: 32717180

pii: S1470-2045(20)30322-3

doi: 10.1016/S1470-2045(20)30322-3

pii:

doi:

Substances chimiques

Oxaliplatin 04ZR38536J

Leucovorin Q573I9DVLP

Fluorouracil U3P01618RT

Banques de données

ClinicalTrials.gov

['NCT01226394']

Types de publication

Clinical Trial, Phase III Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1147-1154

Investigateurs

M Ducreux (M)

D Malka (D)

V Boige (V)

E Benhamou (E)

Commentaires et corrections

Type : CommentIn