9 januari 2018: lees ook dit artikel: 

https://kanker-actueel.nl/s-1-plus-irinotecan-plus-bevacizumab-versus-mfolfox6-of-capeox-plus-bevacizumab-voor-uitgezaaide-darmkanker-geeft-betere-overall-overleving-en-minder-bijwerkingen.html

29 januari 2017: Bron: ECCO 2017

S-1 een oraal in te nemen chemo, vergelijkbaar met Xeloda - capecitabine vermindert het hand- voetsyndroom (pijnlijke uiteinden van voeten en handen tot blaren en bloedens aan toe vaak) (71% versus 45%) bij oudere darmkankerpatienten (mediane leeftijd 71 jaar) met gevorderde darmkanker. En als het wel optreed (nog altijd bij 45% van de patiënten) ook minder ernstig. Zonder dat dit de effectiviteit van de behandeling aantast.

Dit blijkt uit promotie onderzoek van dr. Jan Kwakman uit het AMC en zijn studie is onderdeel van de grote Nederlandse SALTO fase III studie (zie ook gerelateerde artikelen of klik op deze link: 

https://kanker-actueel.nl/NL/s-1-een-oraal-middel-succesvol-bij-alvleesklierkanker-wordt-in-fase-iii-studie-in-nederland-onderzocht-bij-dikke-darmkanker.html.

S-1 (IRIS) bestaat uit een combinatie van tegafur, 5-chloro-2,4-dihydroxypyridine en potassium oxonate, samen in een tablet oraal in te nemen

Het AD had een kort interview met dr. Kwakman waarin deze stelt dat deze bevindingen nieuw zijn maar dit is echt niet waar. Misschien nieuw voor Nederland maar S-1 wordt al jaren toegepast in Japan en Azië en staat algemeen bekend en is ook bewezen minder bijwerkingen te geven.

Hier een overzichtstabel van de bijwerkingen uit een reviewstudie uit 2015 (zie onderaan abstract). Teskt gaat verder onder tabel.

Table 2

Outcome of toxicity meta-analysis comparing S-1 versus 5-FU in advanced colorectal cancer.

ToxicityTrialsSBTFBTHeterogeneityOR (95% CI)ModelP value
P valueI 2 (%)
Grade 3-4 neutropenia 3 96/291 143/284 0.73 0 0.49 [0.35, 0.68] Fixed <0.01
Grade 3-4 leucopenia 10 79/734 100/726 0.28 18 0.75 [0.55, 1.04] Fixed 0.08
Grade 3-4 anemia 9 41/712 31/705 0.40 3 1.33 [0.83, 2.15] Fixed 0.24
Grade 3-4 thrombocytopenia 9 15/709 14/702 0.28 21 1.05 [0.51, 2.15] Fixed 0.89
Grade 3-4 diarrhea 12 92/820 49/805 <0.1 64 1.25 [0.58, 2.69] Random 0.57
Grade 3-4 nausea/vomit 10 15/739 38/732 0.56 0 0.41 [0.23, 0.72] Fixed <0.01
Grade 3-4 stomatitis 9 11/716 4/710 0.24 28 2.21 [0.83, 5.88] Fixed 0.11
Treatment-related death 5 4/545 6/542 0.71 0 0.72 [0.24, 2.19] Fixed 0.57

Notes: NA: not available; OR: odds ratio; CI: confidence interval; FBT: 5-fluorouracil-based therapy; SBT: S-1-based therapy.

Kort citaat uit het AD interview:

Minder pijn bij andere chemo

Het is één van de naarste bijwerkingen van chemotherapie: handen en voeten vol blaren en kloven. Promovendus Robert Jan Kwakman aan het AMC in Amsterdam ontdekte dat een ander chemo-middel tot aanzienlijk minder klachten leidt. Vandaag spreekt hij op het European Cancer Congress in Amsterdam hierover.

Waar hebben de patiënten precies last van?
,,Zij kampen met roodheid, zwelling en vervelling van de handpalmen en voetzolen. In ernstige gevallen ontstaan er bloedingen, blaren en kloven. Heel pijnlijk. Handelingen als aankleden en wassen kunnen erg moeilijk worden. Er zijn zelfs patiënten die in een rolstoel naar de polikliniek komen, omdat lopen niet meer gaat. Deze bijwerking wordt het hand-voetsyndroom genoemd. Naar schatting hebben jaarlijks duizenden patiënten er last van." Lees verder het hele interview>>>>>>>>

Abstract van de studie: 

Randomised phase 3 study of S-1 versus capecitabine, with bevacizumab optional in both arms, in the first-line treatment of metastatic colorectal cancer (mCRC), the SALTO study of the Dutch Colorectal Cancer Group staat onderaan artikel

Hier enkele studies gedaan met S-1 bij darmkanker in verschillende stadia en in verschillende combinaties:

Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study).

En deze:

A phase 3 non-inferiority study of 5-FU/l-leucovorin/irinotecan (FOLFIRI) versus irinotecan/S-1 (IRIS) as second-line chemotherapy for metastatic colorectal cancer: updated results of the FIRIS study.

En deze:

Effectiveness and safety of s-1-based therapy compared with 5-Fluorouracil-based therapy for advanced colorectal cancer: a meta-analysis. 

Conclusions. SBT had similar efficacy and better safety than FBT and was an attractive alternative to FBT for patients of ACRC, but further investigations in different populations would be needed to confirm it.

Bij deze laatste studie een lange referentielijst die ook onderaan dit artikel staat.

Hier eerst het abstract van de studie van Jan Kwakman daarna de referentielijst:

Treatment with S-1 results in a significantly lower incidence of Hand-foot syndrome (HFS) compared to capecitabine in patiens with metastatic colorectal cancer (mCRC),, without compromising efficacy

Source: ECCO 2017:

Randomised phase 3 study of S-1 versus capecitabine, with bevacizumab optional in both arms, in the first-line treatment of metastatic colorectal cancer (mCRC), the SALTO study of the Dutch Colorectal Cancer Group

J.J.M. Kwakman, L.H.J. Simkens, J.M. Van Rooijen, A.J. Van de Wouw, O.J.L. Loosveld, G.J.M. Creemers, M.P. Hendriks, M. Los, R.J. Van Alphen, M.B. Polée, E.W. Muller, A.M.T. Van der Velden, T. Van Voorthuizen, M. Koopman, L. Mol, E. Van Werkhoven, C.J.A. Punt

Background: Hand-foot syndrome (HFS) is a common and troublesome side effect of capecitabine. S-1 is an oral fluoropyrimidine with comparable efficacy to capecitabine in gastrointestinal cancers but associated with a lower incidence of HFS in Asian patients (pts). The Dutch SALTO study (NCT01918852) was designed to compare the incidence of HFS between S-1 and capecitabine as 1st line treatment in mCRC pts.

Materials and Methods: In this open-label, multicentre, randomised phase 3 trial, we randomly assigned patients (1:1) with previously untreated mCRC, WHO performance status of 0–2, and planned treatment with fluoropyrimidine monochemotherapy from 27 hospitals in the Netherlands to receive either capecitabine (1250 mg/m2 for patients <70 years; 1000 mg/m2 for patients ≥70 years, twice-daily on days 1–14) or S-1 (30 mg/m2 twice daily on days 1–14), with bevacizumab co-treatment (7.5 mg/kg on day 1) optional in both arms. Cycles are administered every 3 weeks and treatment is continued until disease progression, unacceptable toxicity, or patients refusal. Randomisation was done centrally by minimisation, with stratification for the use of bevacizumab, WHO performance status, serum lactate dehydrogenase, and institution. The primary endpoint is the incidence of any grade HFS, which is assessed prior to each cycle by local investigators and by patients using a diary. A total of 150 pts is required to demonstrate a difference in HFS of ≥20% with 90% power (α = 0.05, 2-tailed test). Secondary endpoints are grade 3 HFS, other toxicities, progression-free survival (PFS), response rate (RR), overall survival (OS).

Results: Between Jan 30, 2014 and July 14, 2015, we randomly assigned 161 patients with a median age of 73 years to receive either capecitabine (n = 81) or S-1 (n = 80). Co-treatment with bevacizumab was planned in 59% of patients in both arms. Median follow-up is 16.1 months, 20 pts (12%) are still on study. The incidence of any grade HFS as assessed by local investigators is 71% in the capecitabine group and 45% in the S-1 group (p 0.0009), and grade 3 HFS is 21% and 4% (p 0.0029), resp. All grade HFS as assessed by 110 pts (preliminary results) is 76% and 53% (p 0.01), and grade 3 HFS is 18% and 5% (p 0.06). Other grade ≥3 toxicity only differs for anorexia (3% and 13%; p 0.03). No significant differences are observed in RR (42% vs 31%; p 0.19) and PFS (median 8.3 vs 8.4 months; p 0.98). Data on OS are not mature.

Conclusions: Treatment with S-1 results in a significantly lower incidence of HFS compared to capecitabine in pts with mCRC, without compromising efficacy. Updated results will be presented at the meeting.

Effectiveness and Safety of S-1-Based Therapy Compared with 5-Fluorouracil-Based Therapy for Advanced Colorectal Cancer: A Meta-Analysis

Gastroenterol Res Pract. 2014; 2014: 146530.
Published online 2014 Nov 30. doi:  10.1155/2014/146530
PMCID: PMC4265705

Effectiveness and Safety of S-1-Based Therapy Compared with 5-Fluorouracil-Based Therapy for Advanced Colorectal Cancer: A Meta-Analysis

Abstract

Objectives. The aim of our study was to compare the efficacy and safety of S-1-based therapy (SBT) versus 5-fluorouracil-based therapy (FBT) for advanced colorectal cancer (ACRC). Methods. A meta-analysis of all eligible randomized controlled trials (RCTs) was performed using RevMan 5.1.0 software. Results. A total of 1625 patients from twelve RCTs including 820 patients in the SBT group and 805 patients in the FBT group were available for analysis. The meta-analysis of overall survival (hazards ratio HR = 0.94, 95% CI = 0.80–1.10), progression-free survival (HR = 1.03, 95% CI = 0.91–1.18), and overall response rate (odds ratio OR = 1.23, 95% CI = 1.00–1.53) showed no statistical significance between SBT group and FBT group. The statistically significant differences in the meta-analysis indicated less incidence of graded 3-4 neutropenia (OR = 0.49, 95% CI = 0.35–0.68) and nausea/vomit (OR = 0.41, 95% CI = 0.23–0.72) in the SBT group, and there was no statistically significant difference in the incidence of grade 3-4 anemia, thrombocytopenia, leucopenia, diarrhea, and treatment-related deaths between two groups. Conclusions. SBT had similar efficacy and better safety than FBT and was an attractive alternative to FBT for patients of ACRC, but further investigations in different populations would be needed to confirm it.

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