Case series of prophylactic S-1-based treatment in solid tumour patients with severe cardiac comorbidity

Background Fluoropyrimidines (FP) are essential in treating many solid tumors, but cardiotoxicity may affect 4-6% of patients and poses a clinical hurdle in patients with severe cardiac comorbidities (1). The CardioSwitch study showed that S-1 -based treatment is safe and effective after previous cardiotoxic events on other FP-based treatments (2). Purpose This retrospective case series presents 12 solid tumour patients with severe and recent cardiac comorbidities, considered contraindication for 5-FU and capecitabine treatment. Thus, patients were treated upfront with S-1–based chemotherapy. There are no previous reports on S-1 in this setting. Results 12 patients were gathered from five European centres, with 5 gastro-oesophageal and 7 colorectal cancers. Indications for treatment were neoadjuvant/conversion in 3, adjuvant in 2, or first-line metastatic in 7. All patients had severe and extensive cardiac comorbidities, which were recent or ongoing, challenging the cornerstone, i.e., the FP-based treatment options. Frailty, older age, previous cancers, and other comorbidities further challenged treatment planning (Table). S-1 was used as monotherapy, with oxaliplatin, irinotecan, bevacizumab, or cetuximab, as well as chemoradiation. Eleven of the patients tolerated S-1-based without any significant cardiotoxicity, whereas one patient had asymptomatic deteriorating LVEF (30%→20%). This was one of several reasons (includes Her2 treatment option, cardiorenal sdr, and acne) for palliative-intent treatment discontinuation after 3 cycles (#12). Another three cases stopped treatment due to adverse events. Of these, one patient (#1) had worsening nausea and diarrhoea grade 3, as well as cerebellar infarction later during the hospital stay and stopped S-1 single after 5 adjuvant cycles out of 8 planned. The second (#6) had deteriorating kidney function and fatigue after 2 neoadjuvant cycles given at a higher than recommended dose of 24mg/m2/bd considering the baseline eGFR of 32. Third (#3) had deterioration of general wellbeing and fatigue after 2 cycles with palliative intent. One patient (#5) stopped after 3 palliative cycles due to bowel obstruction without radiologic progression of any metastatic site. The rest continued treatment until disease progression during first-line treatment (#2, #7, #9), completion of curative-intent treatment (chemoradiation #8 and adjuvant treatment #4), curative metastasectomy (#11), or still ongoing after 8+ cycles (#10). These patients stayed on treatment for 5-25 three-weekly S-1–based cycles. Five patients are alive. Conclusions In patients with solid tumours and recent severe cardiac comorbidities precluding standard fluoropyrimidines, prophylactic S-1–based chemotherapy was feasible and associated with a low rate of cardiotoxicity. This approach allowed delivery of oncologically relevant treatment across curative and palliative settings, highlighting S-1 as a valuable cardio-oncology-adapted alternative.