A phase I trial of surgical resection with biodegradable carmustine (BCNU) wafer placement followed by vaccination..............

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Author(s): J. D. Rudnick,
S. Phuphanich, R. Chu, M. Mazer, H. Wang, N. Serrano, M. Francisco, K.
L. Black, C. Wheeler, J. Yu; Cedars-Sinai Medical Center, Los Angeles,
Background: Our
prior immunotherapy trials demonstrated efficacy in generating a tumor
specific immune response in malignant glioma and the potential for high
tumor-specific toxicity and sustained tumoricidal activity.
Immunotherapy may synergize with chemotherapy and biodegradable
carmustine (BCNU) wafers extend overall survival from 11.6 to 13.9
Methods: We exploited this synergistic effect to
maintain a cytotoxic environment around the tumor milieu. Patients with
high-grade glioma were eligible after maximal resection with
biodegradable carmustine (BCNU) wafer placement. Screening
leukapheresis is used to isolate mononuclear cells which are
differentiated into dendritic cells, pulsed with tumor lysate, and then
3 intradermal vaccines are administered at 2-week intervals. Patients
continued systemic chemotherapy after vaccine or at progression.
Results: Eighteen
patients have been enrolled (7 Male, 11 Female) between April 2007 and
February 2009 with one screen failure and two patients with clinical
progression prior to vaccination. The median patient age was 57 years
(26 to 74 ) and median Karnofsky performance status was 90% (80-100).
The histology included 3 newly diagnosed glioblastoma multiforme (GBM),
8 recurrent GBM, 2 newly diagnosed anaplastic astrocytoma (AA), and 2
recurrent AA. 15 patients were successfully treated by vaccine
injections with 12 patients receiving vaccine every 2 weeks x 3
followed by adjuvant chemotherapy. Our preliminary data on 15 patients
and 39 courses of Dendritic Cell vaccines demonstrate one grade 3
toxicity of fever/chest pain. A stable disease interval of 13 to 90
weeks was observed for patients who received vaccine. The 3 newly
diagnosed GBM patients have stable disease (18 to 71 weeks). In the
recurrent GBM cohort 7/8 patients had progression within 6 months from
the post-vaccination MRI.
Conclusions: This phase I study
demonstrates the safety, feasibility of dendritic cell vaccination with
biodegradable carmustine (BCNU) wafers with one grade 3 AE.
Immunological data is pending to determine potential synergy of
dendritic cell vaccination with intracranial chemotherapy.