Affiliation:
1. Dana‐Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School Boston Massachusetts USA
2. Dana‐Farber Cancer Institute and Harvard Medical School Boston Massachusetts USA
Abstract
AbstractPurposePhase 1 study assessing the safety and toxicity of cabozantinib in combination with topotecan and cyclophosphamide for relapsed osteosarcoma and Ewing sarcoma.MethodsOral cabozantinib (25 mg/m2) was administered daily for 21 (dose level 1) or 14 (dose level −1B) days. Topotecan (0.75 mg/m2) and cyclophosphamide (250 mg/m2) were administered intravenously (IV) on days 1–5. A modified 3+3 design based upon first cycle dose‐limiting toxicities (DLT) was used for dose escalation.ResultsTwelve patients with a median age of 15 (12.9–33.2) years were enrolled (seven with Ewing sarcoma; five with osteosarcoma); all were evaluable for toxicity. At dose level 1, three of six patients developed first cycle DLT: grade 3 epistaxis, grade 3 transaminitis, and prolonged grade 2 thrombocytopenia. Six patients were enrolled on dose level −1B (interrupted cabozantinib, given days 8–21), with one first cycle DLT (grade 3 pneumothorax) observed. Of the 10 response evaluable patients, one had partial response (Ewing sarcoma), seven had stable disease, and two had progressive disease.ConclusionsThe recommended phase 2 doses and schedules for this combination are topotecan 0.75 mg/m2 IV days 1–5, cyclophosphamide 250 mg/m2 IV days 1–5, and cabozantinib 25 mg/m2 days 8–21. Non‐concomitant administration of cabozantinib with cytotoxic therapy in this population has acceptable toxicity, while allowing for potential disease control.
Subject
Oncology,Hematology,Pediatrics, Perinatology and Child Health