A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours

摘要: This phase I study assessed the maximum tolerated dose, dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin paclitaxel anti-tumour activity combination in solid tumours. Cohorts three to six patients were treated escalating doses administered intravenously once daily, days 1–5 q21 days; on day 3, (area under curve (AUC) 5) and/or (175 mg m−2) 2–3 h after end infusion. In all 23 received 600–1000 mg m−2 per paclitaxel. No DLT was observed. The maximal dose 1000 mg m−2 for 1–5, AUC 5 3. Grade III/IV adverse events (n; %): leucopenia (5; 22%), neutropenia (7; 30%), thrombocytopenia (3; 13%) anaemia (1; 4%), peripheral sensory neuropathy (2; 9%), fatigue vomiting 4%) myalgia 4%). belinostat, unaltered by concurrent administration. There two partial responses (one rectal cancer one pancreatic cancer). A third patient (mixed mullerian tumour ovarian origin) showed a complete CA-125 response. addition, stable disease lasting ⩾6 months. well tolerated, no evidence pharmacokinetic interaction. Further evaluation is warranted.