uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Reduced-dose combination chemotherapy (S-1 plus oxaliplatin) versus full- dose monotherapy (S-1) in older vulnerable patients with metastatic colorectal cancer (NORDIC9): a randomised, open-label phase 2 trial
Odense Univ Hosp, Dept Oncol, DK-5000 Odense C, Denmark;Odense Univ Hosp, Acad Geriatr Canc Res AgeCare, Odense, Denmark;Univ Southern Denmark, Dept Clin Res, Odense, Denmark.
Haukeland Hosp, Dept Oncol, Bergen, Norway.ORCID iD: 0000-0002-8204-3949
Reg Hosp West Jutland, Dept Oncol, Herning, Denmark.
Trondheim Reg & Univ Hosp, Dept Oncol, Trondheim, Norway.
Show others and affiliations
2019 (English)In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 4, no 5, p. 376-388Article in journal (Refereed) Published
Abstract [en]

Background: Older or vulnerable patients with metastatic colorectal cancer are seldom included in randomised trials.The multicentre NORDIC9 trial evaluated reduced-dose combination chemotherapy compared with full-dose monotherapy in older, vulnerable patients.

Methods: This randomised, open-label phase 2 trial was done in 23 Nordic oncology clinics and included patients aged 70 years or older with previously untreated metastatic colorectal cancer who were not candidates for full-dose combination chemotherapy. Patients were block randomised (1: 1) using a web-based tool to full-dose S-1 (30 mg/m(2) orally twice daily on days 1-14 every 3 weeks) followed by second-line treatment at progression with irinotecan (250 mg/m(2) intravenously on day 1 every 3 weeks or 180 mg/m(2) intravenously on day 1 every 2 weeks) or reduceddose combination chemotherapy with S-1 (20 mg/m(2) orally twice daily on days 1-14) and oxaliplatin (100 mg/m(2) intravenously on day 1 every 3 weeks) followed by second-line treatment at progression with S-1 (20 mg/m(2) orally twice daily on days 1-14) and irinotecan (180 mg/m(2) intravenously on day 1 every 3 weeks). Use of bevacizumab (7.5 mg/kg intravenously on day 1 of each cycle) was optional. Treatment allocation was not masked and randomisation was stratified for institution and bevacizumab. The primary outcome was progression-free survival. Survival analyses were by intention to treat and safety analyses were done on the treated population. This trial is registered with EudraCT, number 2014-000394-39, and is closed to new participants.

Findings: From March 9, 2015, to Oct 11, 2017, 160 patients with a median age of 78 years (IQR 76-81) were randomly assigned to full-dose monotherapy (n=83) or reduced-dose combination chemotherapy (n=77). At data cutoff (Sept 1, 2018; median follow-up 23.8 months [IQR 18.8-30.9]), 81 (98%) patients in the full-dose monotherapy group and 71 (92%) patients in the reduced-dose combination group had progressed or died. Median progression-free survival was significantly longer with reduced-dose combination chemotherapy (6.2 months [95% CI 5.3-8.3]) than with full-dose monotherapy (5.3 months [4.1-6.8]; hazard ratio [HR] 0.72 [95% CI 0.52-0.99]; p=0.047). Toxicity was evaluated in 157 patients who received treatment. Significantly more patients in the full-dose monotherapy group (51 [62%] of 82 patients) experienced at least one grade 3-4 adverse event than in the reduced-dose combination group (32 [43%] of 75 patients; p=0.014). Grade 3-4 diarrhoea (12 [15%] vs two [3%]; p=0.018), fatigue (ten [12%] vs three [4%]; p=0.083), and dehydration (five [6%] vs none; p=0.060) were more frequent in the full-dose monotherapy group than in the reduced-dose combination group. Treatment-related deaths occurred in three patients during firstline treatment and three patients during second-line treatment (two in the full-dose monotherapy group vs one in the reduced-dose combination group in both cases).

Interpretation: Reduced-dose combination chemotherapy with S-1 and oxaliplatin for older, vulnerable patients with metastatic colorectal cancer was more effective and resulted in less toxicity than full-dose monotherapy with S-1. Reduced-dose combination chemotherapy could be a preferred treatment for this population.

Place, publisher, year, edition, pages
ELSEVIER INC , 2019. Vol. 4, no 5, p. 376-388
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-382373DOI: 10.1016/S2468-1253(19)30041-XISI: 000463786300023PubMedID: 30852136OAI: oai:DiVA.org:uu-382373DiVA, id: diva2:1307217
Funder
Swedish Cancer SocietyAvailable from: 2019-04-26 Created: 2019-04-26 Last updated: 2019-04-26Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Berglund, ÅkeGlimelius, Bengt

Search in DiVA

By author/editor
Liposits, GaborBerglund, ÅkeGlimelius, Bengt
By organisation
Experimental and Clinical Oncology
In the same journal
The Lancet Gastroenterology & Hepatology
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 17 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf