title: Pediatric phase II trials of poly-ICLC in the management of newly diagnosed and recurrent brain tumors.
abstract: Brain tumors are the most common solid tumor diagnosed in childhood that account for significant morbidity and mortality. New therapies are urgently needed; hence, we conducted the first ever prospective open-label phase II trials of the biological response modifier, poly-ICLC, in children with brain tumors. Poly-ICLC is a synthetic double-stranded RNA that has direct antiviral, antineoplastic, and immune adjuvant effects. A total of 47 children representing a variety of brain tumor histopathologic subtypes were treated with poly-ICLC. On the basis of the results of the initial phase II trial, an expanded prospective phase II trial in low-grade glioma (LGG) has been initiated. MRI was used to acquire volume-based measures of tumor response. No dose-limiting toxicities have been observed. In the initial study 3 of 12 subjects with progressive high-grade gliomas (HGGs) responded, and 2 of 4 children with progressive LGG experienced stable disease for 18 to 24 months. In the follow-up LGG phase II study, 2 of 5 LGG patients were stable over 18 months, with 1 stable for 6 months. Overall 5 of 10 LGG patients have responded. On the basis of low toxicity and the promising LGG response, poly-ICLC may be effective for childhood LGG, and the results justify biomarker studies for personalization of poly-ICLC as a single agent or adjuvant.
authors.affiliation: Departments of *Pediatrics §Neuro-oncology #Pathology (Division of Neuropathology), Moores UCSD Cancer Center †Pediatrics ‡Neurosciences/Pediatrics, Rady Children's Hospital, University of California San Diego, La Jolla, CA ∥Oncovir Inc. ¶Children's Oncology Group, Childrens Hospital of Orange County, Orange, CA **Department of Pediatrics, Emory University, AFLAC Cancer Center, Children's Healthcare of Atlanta, Atlanta, GA.
authors.forename: Lisa L R
authors.initials: LL
authors.lastname: Hartman
authors.forename: John R
authors.initials: JR
authors.lastname: Crawford
authors.forename: Milan T
authors.initials: MT
authors.lastname: Makale
authors.forename: Mehrzad
authors.initials: M
authors.lastname: Milburn
authors.forename: Shweta
authors.initials: S
authors.lastname: Joshi
authors.forename: Andres M
authors.initials: AM
authors.lastname: Salazar
authors.forename: Beth
authors.initials: B
authors.lastname: Hasenauer
authors.forename: Scott R
authors.initials: SR
authors.lastname: VandenBerg
authors.forename: Tobey J
authors.initials: TJ
authors.lastname: MacDonald
authors.forename: Donald L
authors.initials: DL
authors.lastname: Durden
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007223:Infant; D018810:Magnetic Resonance Angiography; D008297:Male; D060787:Neoplasm Grading; D011070:Poly I-C / Q000008:administration & dosage* / Q000009:adverse effects; D011107:Polylysine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D011107:Polylysine; C019531:poly ICLC; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C