A Phase I Trial of Oral Ridaforolimus (AP23573; MK-8669) in Combination with Bevacizumab for Patients with Advanced Cancers

作者：Nemunaitis J^*; Hochster H S; Lustgarten S; Rhodes R; Ebbinghaus S; Turner C D; Dodion P F; Mita M M

来源：Clinical Oncology, 2013, 25(6): 336-342.

DOI：10.1016/j.clon.2013.02.005

• Bevacizumab
• mammalian target of rapamycin
• phase I
• ridaforolimus
• solid tumours

Aims: This phase I dose-escalation study was designed to evaluate the combination of the mammalian target of rapamycin inhibitor ridaforolimus with the vascular endothelial growth factor inhibitor bevacizumab. %26lt;br%26gt;Materials and methods: Seventeen adult patients with refractory advanced solid tumours received oral ridaforolimus (30 or 40 mg) once daily for 5 days per week (QDx5/wk) combined with intravenous bevacizumab (10 mg/kg every 2 weeks [Q2wk] or 15 mg/kg every 3 weeks [Q3wk]). Patients were evaluated for dose-limiting toxicities, safety and anti-tumour activity. %26lt;br%26gt;Results: A 40 mg dose of ridaforolimus with either bevacizumab dosing schedule was the recommended phase II dose. No dose-limiting toxicities were reported; the most common drug-related adverse events were mucosal inflammation and anorexia. Seven patients, with clinical features that included primary tumour of the abdominal origin (colorectal, pancreatic or gynaecological cancers) and previous abdominal radiotherapy, reported serious adverse events related to bowel perforations. There were no objective responses, but 65% of patients had a best response of stable disease. %26lt;br%26gt;Conclusion: Oral ridaforolimus (40 mg QDx5/wk) is feasible to combine with standard doses of bevacizumab, although careful patient selection would be needed to mitigate the risk of bowel perforation-related adverse events. Combination therapy produced prolonged stable disease in several heavily pretreated patients.

• 出版日期2013-6