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

9577 General Poster Session (Board #43H), Sun, 8:00 AM-12:00 PM
Ifomide/pirarubicin/etoposide/carboplatin (ITEC) as second-line chemotherapy
for hepatoblastoma. Presenting Author: Eiso Hiyama, Hiroshima
Univerisity, Natural Science Center for Basic Research and Development,
Hiroshima, Japan
Background: The Japanese Study Group for Pediatric Liver Tumor is running
cooperative treatment studies on hepatoblastoma (HBL) since 1991. The
main aim in JPLT-1 study was to evaluate the efficacy of cisplatin/
pirarubicin (CITA). A total of 145 cases were registered and their 5-year
overall survival (OS) and event-free survival (EFS) were 73.4% and 66%,
respectively (J Pediatr Surg 37: 851-6, 2002). Then, JPLT-2 protocol, in
which CITA is kept as the first-line treatment, and ifomide, etoposide,
pirarubicin, and carboplatin (ITEC) is the second-line regimen for CITAresistant
cases, was launched to evaluate the cure rate of risk-stratified
HBL: standard risk HBL (a tumor involving three or fewer sectors of the
liver) and high risk HBL (a tumor involving all sectors of the liver or with
metastasis). Methods: In JPLT-2, 281 HBL cases were registered in JPLT-2
between 1999 and 2010, and 69 cases underwent ITEC protocol due to
poor response to the CITA regimen. To evaluate the efficacy of the ITEC
regimen, surgical resectability and outcome of these 69 patients who
underwent this treatment. Results: These 69 cases were divided into 53
high-risk (metastatic, involvement of all sectors of the liver, vascular
invasion and/or extra-hepatic intra-abdominal disease) and 16 standardrisk
HBL (all others). All cases were initially treated with the CITA regimen
and then underwent the ITEC regimen due to poor response to CITA.
Complete resection of the liver tumor could be achieved in 48 patients
(69.6%) consisting of 13 (81%) standard, 35 (66%) high- risk cases. The
5-year OS and EFS of the cases with standard risk HB were 96% and 76%,
while that of the cases with high risk HB was 54% and 34%. The late phase
complications in 281 cases were 3 cases with maldevelopment, 13 with
cardiac complications, 20 with ototoxicity and 5 with second malignancies.
Conclusions: As compared with the CITA-sensitive cases, ITEC regimen
achieved similar rates of survival for CITA-resistant cases both in standard
and high-risk HBL cases, indicating ITEC is effective as a second-line
chemotherapeutic regimen for HBL.
9579 General Poster Session (Board #44B), Sun, 8:00 AM-12:00 PM
A phase II trial of docetaxel and irinotecan (DI) in children and young adults
with recurrent or refractory Ewing sarcoma family of tumor (ESFT).
Presenting Author: Jong Hyung Yoon, Center for Pediatric Oncology,
National Cancer Center, Goyang, South Korea
Background: Patients with ESFT resistant to second-line therapy, such as
topotecan plus cyclophosphamide, have a dismal prognosis and few
therapeutic options. Docetaxel (D), a microtubule inhibitor, demonstrated
activity in patients with ESFT (Zwerdling T et al. Cancer 2006:106:1821-
1828). Irinotecan (I), a toposiomerase I inhibitor, is being evaluated in
clinical trials for ESFT. Despite the different mechanisms of action of D and
I, and their activities as a single-agent against ESFT, DI combination has
not been previously evaluated in ESFT. Thus, we prospectively performed a
single-arm, phase II trial of DI in a single center in Korea. Methods: Patients
�30 years with ESFT, who failed second-line therapy, were eligible for the
study. D was administered IV over 60 minutes at a dose of 100 mg/m2 on
Day 1, and I at a dose of 80 mg/m2 over 90 minutes on Days 1 and 8 of a
21-day cycle until disease progression. The primary end-point was objective
response assessed by RECIST; the secondary end-point was safety. All
toxicities were graded according to the National Cancer Institute’s Common
Toxicity Criteria (version 4.0). Results: Of seven eligible patients (4 males;
median age, 17 years (range 5-21)), 4 were recurrent/refractory cases, and
3 refractory cases. Median number of previous regimens was 6 (range 3-6).
One CR, 1 PR, and 5 PD were obtained by DI combination (median number
of cycles, 2 (range 1-15)), with objective response (CR�PR) rate of 2/7
(28.6%). One patient with PR achieved CR with subsequent surgery. CR of
these two patients lasted 8.9 months and 10.6 months. Of all seven
patients fully evaluable for toxicity, grade 4 neutropenia occurred in 7
(100%); grade 3 and 4 thrombocytopenia in 1 (14%) and 6 (86%),
respectively; grade 3 pericardial effusion, paresthesia, motor weakness,
oral mucositis, each in one (14%). Two patients required �1 dose delay; 2
required �1 dose reduction due to adverse events, but no one experienced
treatment-related mortality. Conclusions: DI combination demonstrated
activity in children and young adults with ESFT who were heavily pretreated,
and was feasible.
Pediatric Oncology
625s
9578 General Poster Session (Board #44A), Sun, 8:00 AM-12:00 PM
Cell cycle and apoptosis regulatory protein (CARP)-1 expression in neuroblastoma.
Presenting Author: Santosh S. Hanmod, Children’s Hospital of
Michigan, Detroit, MI
Background: Neuroblastoma (NB) is the most common extra-cranial solid
tumor in children. The prognosis for patients with high risk NB is still poor.
Study of additional prognostic factors will enhance current understanding
of the tumor biology and risk stratification. CARP-1 is a recently identified
molecule mediating apoptosis signaling by agents like doxorubicin and
etoposide. Since these agents are used in the front line treatment of NB, we
tested whether CARP-1 expression could be another prognostic factor in
NB. Methods: CARP-1 expression was examined by Western blot in a pair of
NB cell lines, SK-N-SH and SK-N-SH Dox. We reviewed medical records of
patients with NB at Children’s Hospital of Michigan from 2000-2009 and
examined CARP-1 expression by immune-histochemistry in the archived,
formalin fixed paraffin embedded NB tissues. CARP-1 expression was
recorded as positive or negative. Correlation of CARP-1 expression and
progression free survival (PFS) was calculated. Results: CARP-1 expression
was detected in SK-N-SH but not SK-N-SH Dox, a doxorubicin-resistant
derivative of SK-N-SH, suggesting that resistance to doxorubicin is associated
with decreased level of CARP-1 expression in NB cells. Of the 30
cases studied, 53 % (16/30) expressed CARP-1. There was no significant
difference in N-myc amplification status (13% vs.14%, p�0.3), or
proportion of unfavorable Shimada histology (60% vs. 64%, p�0.5)
between CARP-1 positive vs. negative groups. Twenty three percent (7/22)
patients progressed or relapsed, including 2/16 (13%) in CARP-1 positive
group vs. 5/14 (36%) in CARP-1 negative group (p�0.1). There was no
significant difference in the PFS at 1 year (94% vs.79%, p�0.2) and 3
year (86% vs.71%, p�0.2) between CARP-1 positive vs. negative groups.
Conclusions: CARP-1 expression was decreased in doxorubicin resistant NB
cell line. CARP-1 expression was detected in approximately half (53%) of
NB tumors. Patients with NB who expressed CARP-1 showed trend towards
better 1- & 3-year PFS as compared to those who did not express CARP-1,
however, the results are not statistically significant which could be due to
the small sample size. Further study with a larger number of patients is
warranted to clarify these findings.
9580 General Poster Session (Board #44C), Sun, 8:00 AM-12:00 PM
Assessment of peripheral blood T regulatory cells (Tregs) in PNET/Ewing
sarcoma: A prospective study. Presenting Author: Tilak Tvsvgk, Dr. B.R.A.,
IRCH, New Delhi, India
Background: Tregs in bone marrow have been previously evaluated in PNET
patients; however, data on peripheral blood ccirculating Tregs is lacking.
The objective of our study was to determine baseline Treg frequency in
PNET patients and correlate the same with patient characteristics and
outcome. Methods: Samples of 5ml venous blood were obtained from 38
newly diagnosed PNET patients at diagnosis along with six healthy controls.
Flow cytometric analysis was done for detecting Treg cells
[CD4�CD25�FoxP3�]. Results: Thirty-eight patients with median age 17
years; male/female ratio of 5.5:1 had significantly higher baseline Tregs
than healthy controls [9.17%�.3.08 vs 3.16�1.49%; p��0.0001].
Eight patients (21.1%) had fever at baseline presentation. The disease was
extra-skeletal in one and metastatic at baseline in 11 (28.9%) patients.
Ten patients relapsed on standard protocol of therapy and seven died. The
median Treg frequency was 8.84% (Range: 2.49-16.31). When the Tregs
were categorized as high and low based on the median value, patients with
fever had a significantly higher Tregs than those without fever
[11.3%�.3.5% vs 8.6% �. 2.7%; p�0.02]. No significant association of
peripheral blood Treg cells frequency was noted with other factors like age,
sex, metastatic disease, relapse or death. The EFS was 55% and OS 70%
of the entire cohort at a median follow up of 14 months. There was no
significant difference in the EFS or OS between the high and low Treg cell
groups [EFS- 52% vs 64%; p�0.99 and OS-75% vs 70%; p�0.26].
Conclusions: This is the first study on circulating Tregs in PNET, and it
shows that the peripheral blood Treg frequencies are higher in these
patients as compared to healthy controls. Further, PNET patients with fever
had significantly higher Treg frequency. However, Tregs did not differ with
respect to metastatic disease at presentation, EFS or OS.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.