14 september 2022: lees ook dit artikel: https://kanker-actueel.nl/hypec-hyperthermische-intraperitoneale-chemotherapie-met-mitomycine-c-naast-operatie-voor-lokaal-gevorderde-darmkanker-stadium-iv-verbetert-ziektecontrole-met-10-procent-op-3-jaars-meting.html

28 januari 2021: Bron: The Lancet

Altijd is gedacht dat een HIPEC = hyperthermische intraperitoneale chemotherapie naast een operatie van uitgezaaide darmkanker met uitzaaiingen in het buikvlies de overall overleving zou verbeteren. Zo wordt een HIPEC bij in het buikvlies uitgezaaide eierstokkanker gezien als de enige genezende behandeling bij dat stadium van de ziekte. Echter nu blijkt uit een grote langjarige Europese studie waaraan ook diverse Nederlandse ziekenhuizen deelnamen dat op oxaliplatine gebaseerde hyperthermische intraperitoneale chemotherapie (HIPEC) tijdens een zogeheten cytoreductieve chirurgie = een operatie waarbij zoveel mogelijk tumorweefsel wordt weggehaald en het buikvlies wordt schoongeschraapt geen extra overall overleving laat zien bij in het buikvlies uitgezaaide darmkanker.

De mediane overall overleving was na mediane follow-up van 63,8 maanden (IQR 53,0-77,1) 41,7 maanden (95% BI 36,253,8) in de cytoreductieve chirurgie plus HIPEC-groep en 41,2 maanden (35 · 1-49 · 7) in de groep met alleen cytoreductieve chirurgie (hazard ratio 1 · 00 [95 · 37% BI 0 · 63-1 · 58]; gestratificeerde log-rank p = 0 · 99).

Het percentage postoperatieve complicaties na 60 dagen was hoger met een HIPEC. (34 [26%] of 131 vs 20 [15%] of 130; p=0·035).

Het studierapport is gepubliceerd in The Lancet:

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial

Published:January 18, 2021DOI:https://doi.org/10.1016/S1470-2045(20)30599-4
 

Summary

Background

The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone.

Methods

We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18–70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m 2) or open (460 mg/m 2) abdomen techniques, and systemic chemotherapy (400 mg/m 2 fluorouracil and 20 mg/m 2 folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.govNCT00769405, and is now completed.

Findings

Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0–77·1), median overall survival was 41·7 months (95% CI 36·2–53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1–49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63–1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035).

Interpretation

Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases.

Funding

Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.

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