In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 2010-2010
Abstract:
2010 Background: Diffuse intrinsic pontine glioma (DIPG) represents one of the most deadly central nervous system tumors of childhood with a median survival of less than 12 months. Convection-enhanced delivery (CED) has been recently hypothesized as a means for augmenting distribution of therapeutic agents within the brain stem. We conducted this study to evaluate CED in children with DIPG. Methods: We performed a standard 3+3 phase I, open-label, dose escalation study in patients with non-progressive DIPG 4 to 14 weeks post-completion or radiation therapy. Seven dose levels of a single injection of 124 I-8H9 (range 0.25 to 4.0 mCi, 250 to 4000 mcl) were studied. Results: 25 children were treated. The average age at enrollment 8 years old (range 3-17). There was no dose limiting toxicity (DLT) and adverse events were limited to grade 1 or 2 (CTCAE v4.0). Estimations of distribution volumes were dose dependent and ranged from 1.5 to 20.1 cm 3 . The mean volume of distribution/volume of infusion (Vd/Vi) was 3.4 (SD 1.2). The mean lesion absorbed dose was 1527 rad/mCi. The mean tumor coverage on dose level 7 was 107%. Conclusions: CED in the brain stem of children with DIPG who were previously irradiated is a safe therapeutic strategy. Up to 4 mCi of 124 I-8H9 was well tolerated. An infusion volume of 4000 mcl appears to be a reasonable single dose for good tumor coverage. PET-based dosimetry validates the conceptual basis for direct drug delivery. Based on our finding CED merits further exploration in early phase clinical trials for children with DIPG. Clinical trial information: NCT01502917.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.2010
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
