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9 december 2011: Bron: J Neurooncol. 2011 Oct 4. [Epub ahead of print]

Voor kinderen met een inoperabele hersentumor - glioblastoom van de hersenstam is er eigenlijk geen hoop meer en tot nu toe geen genezende behandeling voor gevonden. Nu blijkt uit een evaluatie van een deelstudie uit een grotere fase II studie dat de aanpak met een vaccin dat synthethisch is gemaakt en werd gegeven naast bestraling enkele kinderen in een totale of gedeeltelijke remissie bracht. En 4 van de 5 kinderen die goed reageerden op deze aanpak leven/leefden langer dan een jaar. wat bij deze vorm van een hersentumor lang is.

Het abstract van de fase II studie vermeld dat het einddoel niet is bereikt, maar uit het abstract van de deelstudie wordt daarentegen gesproken over immunologische reacties met klnische effectiviteit. Hier achtereenvolgens de abstracten van de studies.

A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study

Source: J Neurooncol. 2011 Oct 4. [Epub ahead of print]

A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study.

Warren KE, Gururangan S, Geyer JR, McLendon RE, Poussaint TY, Wallace D, Balis FM, Berg SL, Packer RJ, Goldman S, Minturn JE, Pollack IF, Boyett JM, Kun LE.

Source

Pediatric Oncology Branch, National Cancer Institute, Building 10 CRC, Room 1-5750, Bethesda, MD, 20892, USA, warrenk@mail.nih.gov.

Abstract

To estimate the sustained (≥8 weeks) objective response rate in pediatric patients with recurrent or progressive high-grade gliomas (HGG, Stratum A) or brainstem gliomas (BSG, Stratum B) treated with the combination of O6-benzylguanine (O6BG) and temozolomide(®) (TMZ). Patients received O6BG 120 mg/m(2)/d IV followed by TMZ 75 mg/m(2)/d orally daily for 5 consecutive days of each 28-day course. The target objective response rate to consider the combination active was 17%. A two-stage design was employed. Forty-three patients were enrolled; 41 were evaluable for response, including 25 patients with HGG and 16 patients with BSG. The combination of O6BG and TMZ was tolerable, and the primary toxicities were myelosuppression and gastrointestinal symptoms. One sustained (≥8 weeks) partial response was observed in the HGG cohort; no sustained objective responses were observed in the BSG cohort. Long-term (≥6 courses) stable disease (SD) was observed in 4 patients in Stratum A and 1 patient in Stratum B. Of the 5 patients with objective response or long-term SD, 3 underwent central review with 2 reclassified as low-grade gliomas. The combination of O6BG and TMZ did not achieve the target response rate for activity in pediatric patients with recurrent or progressive HGG and BSG.

PMID:: 21968943; [PubMed - as supplied by publisher]

A multipeptide vaccination approach in children with glioma is well tolerated and has evidence of immunological and clinical activity.

RESULTS OF A PILOT STUDY TO EVALUATE THE EFFECTS OF VACCINATIONS WITH HLA-A2-RESTRICTED GLIOMA ANTIGEN-PEPTIDES IN COMBINATION WITH POLY-ICLC FOR CHILDREN WITH NEWLY DIAGNOSED MALIGNANT BRAIN STEM GLIOMAS, NON-BRAINSTEM HIGH-GRADE GLIOMAS, OR RECURRENT UNRESECTABLE GLIOMAS

Ian F. Pollack¹, Regina I. Jakacki¹, Lisa H. Butterfield², Hideho Okada²

¹Children's Hospital of Pittsburgh, Pittsburgh, PA; ²University of Pittsburgh Cancer Institute, Pittsburgh, PA

Malignant astrocytomas of the brainstem and cerebral hemispheres have a poor prognosis despite current treatments, and new therapeutic approaches are needed. Based on our findings regarding antigen expression profiles of childhood gliomas, we initiated a pilot trial of subcutaneous vaccinations with synthetic peptides for glioma-associated antigen (GAA) epitopes emulsified in Montanide-ISA-51 every 3 weeks for 8 courses, and intramuscular administration of poly-ICLC in HLA-A2+ children with newly diagnosed brainstem glioma (BSG), cerebral high-grade glioma (HGG), or recurrent glioma. GAAs were EphA2, interleukin (IL)-13 receptor-α2, and survivin. Primary endpoints were safety and T cell responses against vaccine-targeted GAAs, assessed by ELISPOT and tetramer analysis. Treatment response was evaluated clinically and by MRI. To date, 18 children have been enrolled: 10 with newly diagnosed BSGs treated with irradiation, 4 with newly diagnosed HGGs treated with irradiation and concurrent chemotherapy, and 4 with recurrent gliomas. No dose-limiting toxicity has been encountered. One child with a BSG had transient tumor enlargement 4 months after beginning vaccination (7 months post-irradiation) that later regressed and culminated in a sustained partial response (PR), consistent with pseudoprogression. Two other children with BSG who had pseudoprogression and subsequent stabilization also remain alive > 1 year from diagnosis without further intervention. Principal toxicities have included injection site reactions and low-grade fevers, which have been mild. Among 16 patients evaluable for response, 12 had sustained stable disease, 1 had a PR, and 1 has a continuing complete response after surgery. Seven of 10 BSG patients have survived > 11 months after diagnosis. ELISPOT analysis, completed in 5 children to date, showed response to IL13Rα2 (n = 4), EphA2 (n = 2), and survivin (n = 1). Tetramer responses to IL13Rα2 and EphA2 were also noted. Our preliminary results demonstrate that a multipeptide vaccination approach in children with glioma is well tolerated and has evidence of immunological and clinical activity.

Neuro-Oncology, Volume 13 Supplement 3, ISSN 1522-8517 (Print); ISSN 1523-5866 (Online)

immuuntherapie, vaccin, hersentumoren