Patients randomised to TACE plus sorafenib were started on 400 mg/day sorafenib 2–3 weeks prior to first TACE to confirm tolerability to sorafenib, to normalise tumour neovasculature for efficient TACE response and to suppress the VEGF increase after the TACE procedure. Sorafenib was discontinued for 2 days before and 2 days after each TACE session.
TACE in both groups consisted of intra-arterial injection of lipiodol plus epirubicin or miriplatin,28 (link)followed by injection of an embolic agent (Gelpart) to interrupt blood flow. Selection of anticancer agent (epirubicin or miriplatin) was decided by the sites/investigators; however, the same agent must be used at the repeated TACE sessions. Therefore, sites were included in the one of the stratification factors to avoid any imbalance. When necessary in treating very large tumours, split TACE was allowed within 4–6 weeks of the first TACE session. First image was taken 4 weeks after split TACE was performed. Repeat TACE with the same anticancer agent was recommended when the two-dimensional measurement of the viable lesion was >50% that of the baseline tumour. TACE was repeated for intrahepatic new lesions measuring >10 mm, which show arterial enhancement with venous washout. If venous washout is not associated with arterial enhancement even in lesions >10 mm, TACE was waited until the time venous washout is confirmed.
Patients in the TACE plus sorafenib group resumed taking 400 mg/day sorafenib 3 days after TACE. If this dose was tolerated, dose increases were allowed to 800 mg/day in a stepwise manner at the discretion of the investigator. At the same dose before re-TACE sorafenib was started after the on-demand TACE. The dose of sorafenib in patients who experienced adverse events (AEs) due to this agent was reduced to 400 mg/day or 400 mg every other day, with patients requiring further dose reduction undergoing dose interruption or discontinued from sorafenib treatment.
Beginning 4 weeks after TACE, tumours were assessed by dynamic CT or MRI every 8 weeks, with tumour marker tests performed at the same times. Treatment was continued until untreatable (unTACEable) progression, progression to meet the TACE refractoriness criteria, unacceptable toxicity or withdrawal of consent.
TACE in both groups consisted of intra-arterial injection of lipiodol plus epirubicin or miriplatin,28 (link)followed by injection of an embolic agent (Gelpart) to interrupt blood flow. Selection of anticancer agent (epirubicin or miriplatin) was decided by the sites/investigators; however, the same agent must be used at the repeated TACE sessions. Therefore, sites were included in the one of the stratification factors to avoid any imbalance. When necessary in treating very large tumours, split TACE was allowed within 4–6 weeks of the first TACE session. First image was taken 4 weeks after split TACE was performed. Repeat TACE with the same anticancer agent was recommended when the two-dimensional measurement of the viable lesion was >50% that of the baseline tumour. TACE was repeated for intrahepatic new lesions measuring >10 mm, which show arterial enhancement with venous washout. If venous washout is not associated with arterial enhancement even in lesions >10 mm, TACE was waited until the time venous washout is confirmed.
Patients in the TACE plus sorafenib group resumed taking 400 mg/day sorafenib 3 days after TACE. If this dose was tolerated, dose increases were allowed to 800 mg/day in a stepwise manner at the discretion of the investigator. At the same dose before re-TACE sorafenib was started after the on-demand TACE. The dose of sorafenib in patients who experienced adverse events (AEs) due to this agent was reduced to 400 mg/day or 400 mg every other day, with patients requiring further dose reduction undergoing dose interruption or discontinued from sorafenib treatment.
Beginning 4 weeks after TACE, tumours were assessed by dynamic CT or MRI every 8 weeks, with tumour marker tests performed at the same times. Treatment was continued until untreatable (unTACEable) progression, progression to meet the TACE refractoriness criteria, unacceptable toxicity or withdrawal of consent.
