HGG-34. EFFICACY AND SAFETY OF DOXORUBICIN PLUS STANDARD THERAPY IN PEDIATRIC HIGH GRADE GLIOMAS: AN OPEN-LABEL MONOCENTRIC NOT-RANDOMIZED PHASE II STUDY

Abstract

DOI: https://doi.org/10.1093/neuonc/noae064.318

Link: https://scholar.google.com/citations?view_op=view_citation&hl=en&user=70cz3rUAAAAJ&cstart=20&pagesize=80&citation_for_view=70cz3rUAAAAJ:qxL8FJ1GzNcC

BACKGROUND
Pediatric high-grade gliomas (pHGGs) comprise a very poor prognosis. Current treatment consists of maximal surgical resection followed by radiotherapy plus concomitant and adjuvant temozolomide (Stupp’s regimen). Despite innovative approaches, outcome remains dismal. Based on the results of previous in vitro and in vivo assays, also considering the wide experience in other pediatric tumors, we aimed to introduce doxorubicin (DOX) as add-on therapy to the standard of care.

METHODS
For testing safety and efficacy of add-on doxorubicin treatment in newly-diagnosed pHGGs, two open-label monocentric not-randomized phase II studies were consequently opened at our institution: GBM TMZ/DOX 2015 (EudraCT 2015-002307-28) and pGBM-WBRT/DOX2020 (EudraCT 2020-005131-74). GBM TMZ/DOX 2015 consisted of DOX 100 mg/mq in 96 hours infusion for 1-3 cycles at 8 week after radiotherapy. pGBM-WBRT/DOX2020 study introduced pan-encephalic radiotherapy followed by DOX 75 mg/mq in 48 hours for 4 cycles starting at week 12 after irradiation, to reduce metastatic relapse rate and to facilitate radiotherapy-induced blood brain barrier opening. Concomitant and adjuvant temozolomide were preserved.

RESULTS
Twenty-one heterogeneous malignant glioma patients (12 hystological diagnosis, 12 males and 8 females, mean age 9.1 ± 4.2 years, age range 2-22 years) were enrolled in the first study. However, for study exiting or for no clinical permissiveness at the time of DOX treatment, only 12 patients were treated with DOX: 2 received three DOX courses and 10 a single course, reducing hematological toxicities. DOX-group showed a longer progression free survival (PFS) compared to standard of care group (median PFS 9 versus 6 months respectively), although this trend was not statistically significative. The second study is on course.

CONCLUSIONS
The adjuvant DOX use in addition to the standard treatment in pHHGs is a practicable option, although to be consolidated, in terms of effectiveness on outcome.