A phase I study of perifosine with temsirolimus for recurrent pediatric solid tumors

• Published in: Pediatric blood & cancer Vol. 64; no. 7
• Main Authors: Becher, Oren J., Gilheeney, Stephen W., Khakoo, Yasmin, Lyden, David C., Haque, Sofia, Braganca, Kevin C., Kolesar, Jill M., Huse, Jason T., Modak, Shakeel, Wexler, Leonard H., Kramer, Kim, Spasojevic, Ivan, Dunkel, Ira J.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.07.2017
• Subjects: 1-Phosphatidylinositol 3-kinase; Adolescent; Age; AKT; AKT protein; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Brain cancer; Brain tumors; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Glioma; Hematology; Humans; Hypercholesterolemia; Inhibitor drugs; Lymphopenia; Male; Maximum Tolerated Dose; Medulloblastoma; mTOR; Neoplasm Recurrence, Local - drug therapy; Neoplasms - drug therapy; Neuroblastoma; Neutropenia; Oncology; Pediatrics; perifosine; Pharmacokinetics; phase I clinical trials; Phosphorylcholine - administration & dosage; Phosphorylcholine - adverse effects; Phosphorylcholine - analogs & derivatives; Phosphorylcholine - pharmacokinetics; Rhabdomyosarcoma; Sirolimus - administration & dosage; Sirolimus - adverse effects; Sirolimus - analogs & derivatives; Sirolimus - pharmacokinetics; Solid tumors; Targeted cancer therapy; temsirolimus; Thrombocytopenia; TOR protein; Toxicity; Young Adult; mTOR; AKT; temsirolimus; phase I clinical trials; perifosine

Background The PI3K/AKT/mTOR pathway is aberrantly activated in many pediatric solid tumors including gliomas and medulloblastomas. Preclinical data in a pediatric glioma model demonstrated that the combination of perifosine (AKT inhibitor) and temsirolimus (mTOR inhibitor) is more potent at inhibit...