We have located links that may give you full text access.
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.
Lancet. Gastroenterology & Hepatology 2019 March 7
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/m2 orally twice daily on days 1-14 every 3 weeks) followed by second-line treatment at progression with irinotecan (250 mg/m2 intravenously on day 1 every 3 weeks or 180 mg/m2 intravenously on day 1 every 2 weeks) or reduced-dose combination chemotherapy with S-1 (20 mg/m2 orally twice daily on days 1-14) and oxaliplatin (100 mg/m2 intravenously on day 1 every 3 weeks) followed by second-line treatment at progression with S-1 (20 mg/m2 orally twice daily on days 1-14) and irinotecan (180 mg/m2 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 first-line 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.
FUNDING: Taiho Pharmaceuticals, Nordic Group, the Danish Cancer Society, the Swedish Cancer Society, Academy of Geriatric Research (AgeCare), and Region of Southern Denmark.
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/m2 orally twice daily on days 1-14 every 3 weeks) followed by second-line treatment at progression with irinotecan (250 mg/m2 intravenously on day 1 every 3 weeks or 180 mg/m2 intravenously on day 1 every 2 weeks) or reduced-dose combination chemotherapy with S-1 (20 mg/m2 orally twice daily on days 1-14) and oxaliplatin (100 mg/m2 intravenously on day 1 every 3 weeks) followed by second-line treatment at progression with S-1 (20 mg/m2 orally twice daily on days 1-14) and irinotecan (180 mg/m2 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 first-line 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.
FUNDING: Taiho Pharmaceuticals, Nordic Group, the Danish Cancer Society, the Swedish Cancer Society, Academy of Geriatric Research (AgeCare), and Region of Southern Denmark.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
Perioperative echocardiographic strain analysis: what anesthesiologists should know.Canadian Journal of Anaesthesia 2024 April 11
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app