9 januari 2018: Lees ook dit artikel:

https://kanker-actueel.nl/s-1-iris-een-oraal-in-te-nemen-chemo-geeft-minder-vaak-en-minder-ernstig-hand-en-voetsyndroom-bij-behandeling-van-vergevorderde-darmkanker.html

9 januari 2018: Bron: Annals of Oncology

Uit de TRICOLORE fase III studie blijkt dat S-1 plus irinotecan plus bevacizumab in vergelijking met mFOLFOX6 of met CapeOX plus bevacizumab betere resultaten geeft op ziektevrije overleving als eerstelijns behandeling bij darmkanker die bij de eerste diagnose al blijkt te zijn uitgezaaid. De studie was opgezet om te kijken of S-1 plus irinitocan plus Avastin 'noninferieur' (zelfde resultaten) zou zijn aan de standaard eerstelijns mFOLFOX6 (6 maanden mFOLFOX) of CAPox (xeloda plus oxaliplatin). Maar de resultaten blijken niet alleen 'noninferieur'maar geven duidelijk een betere ziektevrije tijd met 3,2 maanden meer voor de S-1 groep, nameljik 10,8 maanden voor de controlegroep versus 14,0 maanden voor de S-1 groep. (HR 0.84, 95% CI 0.70 − 1.02; P<0.0001 for non-inferiority, P=0.0815 for superiority). En met minder graad 3 of hogere bijwerkingen.

3,2 maanden langere ziektevrije tijd (= ca. 30 procent!!!!!) plus minder bijwerkingen laat de onderzoekers concluderen dat S-1 plus irinitocan plus bevacizumab / Avastin een nieuwe standaard eerstelijns behandeling zou kunnen / moeten zijn voor uitgezaaide darmkanker bij de eerste diagnose.

Dit is het studie protocol dat is gevolgd en is uitgevoerd wereldwijd in 52 ziekenhuizen, daaronder de resultaten en abstract:

Fig. 1

Study schema

Kernpunten:

This phase III trial was designed to compare the use of oral fluoropyrimidine (S-1) with irinotecan and bevacizumab (n = 241) vs FOLFOX or CAPOX plus bevacizumab (n = 243). The median progression-free survival (the primary endpoint) was not significantly different in patients receiving FOLFOX or CAPOX plus bevacizumab compared with patients receiving S-1 with irinotecan and bevacizumab (10.8 vs 14.0 months).
The combination of S-1, irinotecan, and bevacizumab was noninferior in terms of progression-free survival in patients with metastatic colorectal cancer.

Het studierapport: S-1 and irinotecan plus bevacizumab versus mFOLFOX6 or CapeOX plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer (TRICOLORE): a randomized, open-label, phase 3, non-inferiority trial is tegen betaling in te zien.

Hier het abstract:

S-1 and irinotecan plus bevacizumab is non-inferior to mFOLFOX6 or CapeOX plus bevacizumab with respect to PFS as first-line treatment for mCRC and could be a new standard treatment.

S-1 and irinotecan plus bevacizumab versus mFOLFOX6 or CapeOX plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer (TRICOLORE): a randomized, open-label, phase 3, non-inferiority trial

Y Yamada T Denda M Gamoh I Iwanaga S Yuki H Shimodaira M Nakamura T Yamaguchi H Ohori K Kobayashi ... Show more

Annals of Oncology, mdx816, https://doi.org/10.1093/annonc/mdx816

Published:

27 December 2017

Abstract

Background

Combination therapy with oral fluoropyrimidine and irinotecan has not yet been established as first-line treatment for metastatic colorectal cancer (mCRC). We performed a randomized, open-label, phase 3 trial to determine whether S-1 and irinotecan plus bevacizumab is non-inferior to mFOLFOX6 or CapeOX plus bevacizumab in terms of progression-free survival (PFS).

Patients and methods

Patients from 53 institutions who had previously untreated mCRC were randomly assigned (1:1) to receive either mFOLFOX6 or CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; a 3-week regimen: intravenous infusions of irinotecan 150 mg/m² and bevacizumab 7.5 mg/kg on day 1, oral S-1 80 mg/m² twice daily for 2 weeks, followed by a 1-week rest; or a 4-week regimen: irinotecan 100 mg/m² and bevacizumab 5 mg/kg on days 1 and 15, S-1 80 mg/m² twice daily for 2 weeks, followed by a 2-week rest). The primary endpoint was PFS. The non-inferiority margin was 1.25; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of the control versus the experimental group was less than this margin.

Results

Between June 2012 and September 2014, 487 patients underwent randomization. 243 patients assigned to the control group and 241 assigned to the experimental group were included in the primary analysis. Median PFS was 10.8 months (95% CI 9.6 − 11.6) in the control group and 14.0 months (95% CI 12.4 − 15.5) in the experimental group (HR 0.84, 95% CI 0.70 − 1.02; P<0.0001 for non-inferiority, P=0.0815 for superiority). 157 patients (64.9%) in the control group and 140 (58.6%) in the experimental group had adverse events of grade 3 or higher.

Conclusion

S-1 and irinotecan plus bevacizumab is non-inferior to mFOLFOX6 or CapeOX plus bevacizumab with respect to PFS as first-line treatment for mCRC and could be a new standard treatment.

Clinical trials number

UMIN000007834

darmkanker, S-1, Folofox, xeloda, Avastin, overall overleving, ziektevrije tijd, biujwerkingenprofiel, uitgezaaide darmkanker, irinitocan