Abstract 20P
Background
Fluoropyrimidines (FP) are the cornerstone of adjuvant therapy in colorectal cancer (CRC). Treatment options are very limited for the 4%-6% of patients who experience cardiotoxicity on FP treatment, often leading to permanent FP discontinuation. The CardioSwitch study in patients with various, mostly metastatic, cancers previously showed that switching to S-1-based treatment is feasible.
Methods
This retrospective study included 76 radically operated stage II-IV CRC patients from 8 European centres. Primary endpoint was the feasibility of switching to S-1-based adjuvant therapy after cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) based treatment. Secondary endpoints were safety and survival.
Results
Median age was 66 years, 38 (50%) were male, and 60 (79%) had ECOG PS 0-1. Primary location was colon in 36 (47%) and rectum in 40 (53%). Baseline cardiovascular comorbidities were present in 33 (43%). Treatment was capecitabine-based in 70 (92%), infusional 5-FU in 5 (7%), and bolus 5-FU in 1 (1%), with oxaliplatin added in 30 (40%). Median time to cardiotoxicity was 5 days (range 0-73). Cardiotoxicity occurred during adjuvant treatment in 59 (78%) or during neoadjuvant chemoradiation (CRT) in 17 (22%). Seven CRT patients were switched during preoperative therapy and all other patients were switched during adjuvant treatment. Median number of S-1-based adjuvant cycles received was 7. Three (4%) developed grade 1-2 recurrent cardiotoxicity on S-1-based treatment and other grade 2-4 adverse events were seen in 16 (21%). Three-year DFS rate was 74% and OS rate 88%, with median follow-up 39 months.
Conclusions
S-1-based neoadjuvant CRT and/or adjuvant treatment is safe and feasible after cardiotoxicity on FP-based treatment and enables patients to continue planned adjuvant treatment.
Clinical trial identification
NCT04260269.
Editorial acknowledgement
The medical writers at Meducom BV, The Netherlands, Wilko Coers, PhD and Sandy Field, PhD, who were compensated for their support by Nordic Drugs and Nordic Pharma.
Legal entity responsible for the study
Tampere University Hospital.
Funding
Nordic Drugs and Nordic Pharma.
Disclosure
P.J. Osterlund: Financial Interests, Personal, Advisory Board, Also invited speaker: Amgen; Financial Interests, Personal, Advisory Board, Also invited speaker: AstraZeneca, MSD, BMS; Financial Interests, Personal, Advisory Board, Also invited lecturer: Bayer, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Eisai, Fresenius Kabi, Imedex; Financial Interests, Personal, Advisory Board: Merck, Sanofi, Incyte, Daiichi Sankyo/AstraZeneca, Eisai, Jansen Pharmaceutica; Financial Interests, Personal, Invited Speaker, Roche Finland and Sweden: Roche; Financial Interests, Personal, Invited Speaker, No compensation for advisory boards: Servier; Financial Interests, Personal, Invited Speaker, Also via Medicom: Nordic Drugs/Group; Financial Interests, Personal, Expert Testimony, FIMEA expert testimony: BMS; Financial Interests, Personal, Invited Speaker, Nordic guidelines committee: Danone; Financial Interests, Institutional, Research Grant: Amgen, Servier, Nordic Drugs/Group; Financial Interests, Institutional, Invited Speaker: Incyte, Roche, Pfizer; Non-Financial Interests, Member: Colores patient advocacy group; Non-Financial Interests, Member, Board member: Finnish cancer society. S. Kinos: Financial Interests, Institutional, Research Grant: Nordic Drugs/Pharma; Financial Interests, Personal, Training: Pfizer, MSD, Roche. P. Halonen, L. Soveri, E. Heerva, A. Algars, R. Ristamaki, T. Salminen, M.O. O'Reilly, R.S. McDermott, R. Kallio, R. Röckert, P. Flygare, J. Froedin: Financial Interests, Institutional, Research Grant: Nordic Drug. B. Glimelius: Financial Interests, Institutional, Research Grant: Nordic Pharma.