Key result
Switching to S-1 after fluoropyrimidine cardiotoxicity proves cost-effective vs discontinuation at ~€60,000 per QALY.
Why the study?
Fluoropyrimidine-induced hand-foot syndrome and cardiovascular toxicity often require dose reductions or treatment discontinuation in metastatic colorectal cancer, and the cost-effectiveness of switching to S-1 after these toxicities is unclear.
Is switching to an S-1 based treatment strategy cost-effective compared to reducing dosage or discontinuing therapy in patients with metastatic colorectal cancer who experience cardiovascular toxicity or hand-foot syndrome from initial fluoropyrimidine therapy?
Is switching to an S-1 based treatment strategy cost-effective compared to reducing dosage or discontinuing therapy in patients with metastatic colorectal cancer who experience cardiovascular toxicity or hand-foot syndrome from initial fluoropyrimidine therapy?
Switching to an S-1 based treatment strategy is a cost-effective option for metastatic colorectal cancer patients who develop fluoropyrimidine-induced cardiovascular toxicity or hand-foot syndrome.
Model supports S-1 switch cost-effectiveness after toxicity; leaves open prospective validation before practice change.
BACKGROUND: The fluoropyrimidines 5-fluorouracil (5FU) and capecitabine are the backbone of systemic therapy for metastatic colorectal cancer (mCRC). Side effects include hand-foot syndrome (HFS) and cardiovascular toxicity (CVT), which may necessitate dose reductions or discontinuation of treatment. S-1 (Teysuno®) is an oral fluoropyrimidine that is licensed for use after fluoropyrimidine-induced HFS or CVT as it showed a lower incidence of those toxicities. It can be used as monotherapy or in combination with oxaliplatin or irinotecan. In this study, we assessed the cost-effectiveness of switching from 5FU or capecitabine-based treatment to S-1-based treatment after a patient with mCRC experiences HFS or CVT. PATIENTS AND METHODS: We developed a cohort-level decision analytic model to compare the costs and quality-adjusted life years (QALYs) when hypothetical patients would follow several different treatment strategies. We considered three different scenarios in which patients experienced toxicity on their initial first-line treatment of either CAPOX (1), FOLFOX (2) or capecitabine monotherapy (3), respectively. The step of first-line to second-line is denoted with an arrow (→). We used medication costs and administration costs, a lifelong time axis and compared strategies using incremental cost-effectiveness ratios (ICERs) and net benefit. RESULTS: Costs for treatment administration often exceeded costs for treatment medication. For scenario 1, the ICER of the strategy of switching to SOX → Irinotecan (which was identical to SOX → IRIS) was €60 303 compared with the next best strategy of discontinuation of CAPOX → Irinotecan. This is below the threshold of €80 000/QALY used by the Dutch government for high-impact health conditions. Results of scenario 2 were similar to scenario 1. For scenario 3, the ICER of S-1 → SOX was €92 551 compared with reduced dosage capecitabine monotherapy → CAPOX. CONCLUSIONS: S-1 based treatment strategies can be cost-effective when a treatment switch is required due to HFS or CVT during fluoropyrimidine-based treatment.
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Eekelen et al. (2026) studied metastatic colorectal cancer with fluoropyrimidine-induced hand-foot syndrome or cardiovascular toxicity (n=1,000). Switch to S-1 based treatment vs. Treatment discontinuation or reduced dosage first-line treatment was evaluated on Incremental cost-effectiveness ratio (ICER) (€60,303 per QALY (scenario 1)). Switching to S-1-based strategies after fluoropyrimidine-induced toxicity was cost-effective compared to treatment discontinuation, yielding an ICER of €60,303/QALY for patients starting on CAPOX.
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