Annual Meeting Proceedings Part 1 - American Society of Clinical ...

124s Central Nervous System Tumors
2035 Poster Discussion Session (Board #23), Fri, 1:00 PM-5:00 PM and
4:30 PM-5:30 PM
A phase II trial evaluating tumor penetration of bortezomib in patients with
recurrent malignant gliomas treated prior to surgery and then treated with
bortezomib and temozolomide postoperatively. Presenting Author: Jeffrey
J. Raizer, Northwestern University, Feinberg School of Medicine, Chicago,
IL
Background: NF-Kappa B is one of the mechanisms of resistance for
malignant gliomas. A few trials have assessed bortezomib in the treatment
of malignant gliomas with limited activity. This may in part be due to
limitations in dose escalation from peripheral neuropathy. We performed a
phase II trial with the goal of measuring bortezomib in tumor tissue and also
its effects on NF-Kappa B. Methods: Patients felt to be surgical candidates
were enrolled after signing an IRB approved consent. They were treated
with bortezomib 1.7 mg/m2 IV on day 1, 4 and 8 and then had surgery on
day 8 or 9. Approximately, 14 days post operatively, patients were started
on temozolomide 75 mg/m2 PO on days 1-7 and 14-21; on day 7 and day
21 they received bortezomib 1.7 mg/m2 (1 cycle was 1 month). Treatment
continued until progression. If �1 patient had a PFS at 6 months the trial
would be stopped. Results: 10 patients were enrolled (8 M and 2 F). Median
age and KPS were 50 (42-64) and 90% (70-90). All but 1 patient went to
surgery, one had an intracranial hemorrhage. The median number of cycles
post operatively was 2 (1-4), with two patients discontinuing for wound
infection (post 3 cycles, not restarted due to prolonged delays) and
meningitis (post 2 cycles then withdrew from trial). Six patients are
deceased. Trial was stopped as no patient had a PFS-6. PK analysis
revealed measurable drug levels in tumor tissue. Conclusions: Post operative
treatment with temozolomide and Bortezomib did not have any activity.
Bortezomib can achieve measurable drug levels in tumor but may not be
sufficient for anti-tumor activity. Tissue will be assessed for bortezomib
effects on NF-Kappa B.
2037 Poster Discussion Session (Board #25), Fri, 1:00 PM-5:00 PM and
4:30 PM-5:30 PM
Phase II trial of dose-dense temozolomide as initial treatment for progressive
low-grade oligodendroglial tumors: A multicentric study of the Italian
Association of Neuro-Oncology (AINO). Presenting Author: Roberta Ruda,
Division of Neuro-Oncology, University Hospital San Giovanni Battista,
Turin, Italy
Background: Standard temozolomide has been shown to be active in
progressive low grade gliomas after surgery, whereas few data are available
on the impact of dose dense regimens. Thus, we developed a phase II single
arm multicenter study to evaluate the efficacy and toxicity of a regimen of
dose dense temozolomide in progressive low grade oligodendroglial tumors.
Methods: The inclusion criteria of the study were as follows: 1)biopsyproven
supratentorial WHO grade II oligodendroglioma and oligoastrocytoma;
2)progressive disease, clinically (epileptic seizures)or radiologically;
3)measurable disease on MRI (at least 1 cm); 4)age �18 years; 5)Karnofsky
Performance Status �70. Temozolomide was administered at
150mg/m2 1 week on/1 week off up to a maximum of 18 cycles or
unacceptable toxicity. The primary end-point was response rate (RR)
according to RANO criteria, whereas secondary end-points were clinical
benefit in terms of reduction of epileptic seizures �50%, progression-free
survival (PFS), quality of life and toxicity. Results: From January 2005 until
December 2010 60 patients (median age 39 and median KPS 80) have
been accrued and are now evaluable for response. Response rates on
T2/FLAIR images were as follows: CR 0/60, PR 21/60 (35%), MR 14/60
(23%), SD 21/60 (35%) and PD 4/60 (7%). The clinical benefit was
significant in 29/34 patients (85%). As for toxicity 5/60 (8%) patients
stopped treatment for lymphopenia grade IV, whereas 11/31 patients
(35%) were switched to the standard regimen of temozolomide. PET with
methionine was added to MRI in 17 patients: in 10/17 (59%) a disappearance
or a significant reduction of uptake was observed, being the reduction
of seizures better correlated with the response on PET rather than that on
MRI. 1p/19q codeletion was not associated with either the response or the
clinical benefit, whereas the analysis of MGMT methylation and IDH1
mutations are ongoing. Thirty-nine (65%) patients are still free of tumor
progression. Conclusions: Dose-dense TMZ seems to be active, especially in
terms of clinical benefit, but the myelotoxicity could be a concern.
2036 Poster Discussion Session (Board #24), Fri, 1:00 PM-5:00 PM and
4:30 PM-5:30 PM
Lenalidomide and irinotecan in adults with recurrent malignant gliomas:
Phase I results of the phase I/II trial. Presenting Author: Vinay K. Puduvalli,
University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Patients with recurrent malignant gliomas have limited treatment
options. We previously reported promising results using 6 month
progression free survival [PFS6] endpoint combining irinotecan and thalidomide
compared to historical controls. In this study, we tested the
tolerability and efficacy of Irinotecan combined with Lenalidomide, a more
potent thalidomide analogue with unique antiangiogenic and immunomodulatory
properties. Methods: This phase I portion of the phase I/II study
aimed to determine the maximum tolerated doses (MTD) of irinotecan and
lenalidomide. Eligible patients were adults (��18 y) with recurrent WHO
Grade 3 or 4 gliomas who were not on EIAED, had failed prior radiation
therapy, had a KPS��60, had adequate marrow, renal and hepatic organ
function, no major medical illnesses and no other concurrent malignancies.
Each cycle was designated as 4 weeks in duration. Results: Two of the 4
patients enrolled at the starting dose level of Lenalidomide 10 mg/day on
days 1-21 and irinotecan 200 mg/m2 q2 weeks developed rash as dose
limiting toxicity (DLT). The trial was restarted with no change in irinotecan
dose but with a lowered Lenalidomide dose of 7.5 mg/day for cycle 1 with
escalation to 10 mg/day for cycle 2 and beyond. Of 3 eligible patients
enrolled, no DLTs were noted even after cycle 2. The dose was hence
escalated to Lenalidomide 10 mg/day with unchanged irinotecan dose.
Only 1/6 patients experienced a DLT (pulmonary embolism); however, it
was noted that 4/6 patients required dose reduction of irinotecan to 150
mg/m2 after cycle 1. One patient died during cycle 2 of unknown causes
(autopsy declined) without reports of preceding toxicities. Non DLT
toxicities included neutropenia, leukopenia, hypokalemia, diarrhea, fatigue
and nausea/vomiting. Lenalidomide pharmacokinetic data, obtained by
serial blood draws initially after one dose of the drug on day 0 and
subsequently after irinotecan and lenalidomide dose on day 1 to examine
drug interactions, will be presented. Conclusions: Based on these results,
the maximum tolerated dose was Lenalidomide 10 mg/day on days 1-21
and irinotecan 150 mg/m2 q 2 weeks every 28 days which will be used in
the phase II study that will open shortly.
2038 General Poster Session (Board #12A), Sat, 1:15 PM-5:15 PM
Does pilocytic astrocytoma (PA) in adults have a different prognosis than
PA in children? Presenting Author: Daniel Fernandes Marques, Instituto do
Cancer do Estado de São Paulo, Universidade de São Paulo, São Paulo,
Brazil
Background: Pilocytic astrocytoma (PA) accounts for up to 25% of all brain
tumors in children. A 75% progression-free survival rate at 5 years and
overall survival rates of 95.8% at 10 years have been reported after a
complete resection. However, the incidence in adults is low and the
outcome less well characterized. We conducted a retrospective analysis of
adult PAs identified in order to review the clinical characteristics and
outcome of this neoplasm in this age group. Methods: A descriptive,
cross-sectional study was undertaken in patients over 16 y.o., diagnosed
with PA between January 1990 and December 2010 at our center. Clinical
characteristics, date and extent of surgery, tumor location, postoperative
treatment, complications and recurrences were collected from hospital
records. Results: From May, 1990 to December, 2010, 18 eligible adult
patients (pts) with the diagnosis of PA were identified. Median age was
25,5 (16-52) years, 72,2% female and 83,3% had an ECOG performance
status � 2. The most frequent tumor sites were the cerebellum (44,4%),
followed by the cerebral hemispheres (38%). All patients underwent
surgery as primary treatment, 72% had a complete macroscopic resection
(CMR) and 28% had a partial resection (PR). Two patients received
postoperative radiotherapy: one following a PR and the other after tumor
relapse following a CMR. Two patients relapsed five months and 44 months
after initial complete gross resection. Salvage surgery achieved CMR in
both. With a median follow-up of 89 months, all patients are alive, except
for one who died in the postoperative period due to fungal meningitis. Of
note, none of 5 pts undergoing a partial resection progressed and 3 are alive
for more than 10 years. Conclusions: As it occurs in the pediatric
population, PA in adults seems to carry a similarly favorable prognosis. It is
conceivable that after initial surgical resection a watch and wait type of
approach is appropriate, even following partial resection. The role of
upfront radiotherapy is uncertain and it should probably be left for
progressive tumors.
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