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

640s Sarcoma
10040 General Poster Session (Board #47A), Sun, 8:00 AM-12:00 PM
Gemcitabine/docetaxel for metastatic or locally advanced soft tissue
sarcoma: A retrospective single-center experience. Presenting Author:
Gerlinde Egerer, Department of Hematology, Oncology, and Rheumatology,
Heidelberg University Hospital, Heidelberg, Germany
Background: Soft tissue sarcoma (STS) represent a group of rare malignant
tumors. Survival for patients with disseminated disease is dismal. Gemcitabine/docetaxel
(GD) is a commonly used systemic 2°-line regime in this
setting. Methods: Here we report on our single center experience of GD (G
900 mg/m² or 675 mg/m² d1�8 and D 100 mg/m² d8) in STS. Patients
were retrospectively analysed. Restaging according to RECIST criteria of
primary tumor site and metastases was performed every 3 cycles or on
clinical progression. Progression-free (PFS) and overall survival (OS) were
estimated using the method of Kaplan and Meier. Results: Between 2005
and 2011, 34 STS patients (male�20, female�14, median age 59 years
[range 32-75]) were treated with GD at our institution. Histological
subtypes comprised leiomyo- (n�13), lipo- (n�7), pleomorphic- (n�6),
rhabdomyo- (n�3), synovial sarcoma (n�2), and other subtypes (n�3)
with tumor grades being G1 (n�1), G2 (n�9) and G3 (n�24). Primary
tumor sites included extremities (n�19), abdomen/retroperitoneum (n�10),
trunk (n�3), and others (n�2). Metastases were found in lung (n�26), soft
tissue/solid organs (n�12), bone (n�8) and lymph nodes (n�5). Patients
had received no (n�2),1(n�22), 2 (n�9) or 3 (n�1) previous lines of
CTX. A total number of 158 cycles was administered with a median number
of 6 cycles (range 1-6) per patient. Best response by RECIST criteria after 3
cycles of treatment was PR (n�2, 6%). Disease stabilisation (SD) was
achieved in further 22 subjects, resulting in a clinical benefit rate (CBR) of
70%. Median PFS and OS for the whole population were 7.7 and 15.3
months, respectively. PFS at 6 months was 62%. Patients responding to
therapy had a significantly longer median PFS with 8.6 months (p
�0.0001; HR 33.1) and OS with 22.5 months (p�0.0001; HR 20.2).
Major toxicities included hand-foot syndrome (n�10), febrile neutropenia
(n�7), mucositis (n�7), oedema (n�5), hematological toxicity (n�4) and
polyneuropathy (n�3), leading to dose reductions in 10 patients.
Conclusions: GD is an active regimen in STS with tolerable side effects.
CBR was 70% after 3 cycles. Patients achieving at least SD had a
significantly prolonged PFS and OS.
10042 General Poster Session (Board #47C), Sun, 8:00 AM-12:00 PM
Sarcoligo: Impact of local ablative treatment of oligometastatic sarcomas
on overall survival. Presenting Author: Juliette Thariat, Centre Antoine-
Lacassagne, Nice, France
Background: 40-50% of sarcomas become metastatic. Median survival of
metastatic patients has improved over time. The probably multifactorial
reasons for such improvement are not fully clear. Noteworthy, for patients
with a controlled primary and a limited number of lung metastases,
complete resection of their metastases yields survival rates of up to 40% at
three years. Advances in surgery, radiotherapy and radiofrequency have
fostered the use of local treatments for various metastatic sites (lung, liver,
spine...). Methods: A multicentric retrospective study of the Groupe
Sarcome Francais (GSF-GETO); approved by the nationally-review board
and ethical committee, was conducted to assess the impact of local
ablative treatment on overall survival. Patients who had had oligometastases
(any site, 1-5 synchronous metastases) at diagnostic or during the
course of disease between 2000 and 2010 were included. Results: Median
age of the 243 oligometastatic sarcoma patients was 53 years-old (11-86).
Patients had grade I, II and III in 7.5%, 29.6% and 63.3% of cases,
respectively with various histologies. 69% of patients underwent local
ablative treatment of metastases. Median follow-up was 59 months
(4-212) for living patients. Median overall survival was 51 months (1-348).
On univariate analysis, grade, histology, absence of chemotherapy, local
ablative treatment (surgery, irradiation, radiofrequency or chemoembolisation)
correlated with survival but not age or site of oligometastasis. On
multivariate analyses, grade (hazard ratio HR 0.12 [CI95 0.3-0.6]) and
local ablative treatment (HR 3.8 [CI95 2.1-7.1]) remained significant.
Conclusions: Local ablative treatment of metastases is associated with
better survival in sarcoma patients with oligometastatic disease. The role of
the locoregional treatment of metastases and its impact on quality of life
should be assessed prospectively.
10041^ General Poster Session (Board #47B), Sun, 8:00 AM-12:00 PM
Pharmacokinetic analyses of vorinostat in patients with metastatic soft
tissue sarcoma. Presenting Author: Thomas Schmitt, Department of
Hematology, Oncology, and Rheumatology, Heidelberg University Hospital,
Heidelberg, Germany
Background: New treatment options for patients with metastatic soft tissue
sarcoma (STS) are urgently needed. Preclinical studies suggest activity of
vorinostat (V), a histone desacetylase (HDAC) inhibitor, in STS. Methods:
We initiated a multicenter, open-label, non-randomized phase II trial
(SAHA-I, NCT00918489) to investigate efficacy and safety of V in patients
with metastatic STS failing 1°-line anthracycline-based CTX. Patients were
treated with V 400 mg po QD for 28 days followed by a therapy-free period
of 7 days. Blood samples for pharmacokinetic (PK) analyses were collected
on day 7 of treatment cycle 1. Samples were acquired before and 30, 60,
90, 120, 240, 360, and 480 minutes after oral administration of V.
Plasma- and intracellular concentration of V in peripheral blood mononuclear
cells (PBMCs) was determined by mass spectrometry. Statistical
differences were assessed by Wilcoxon matched-pairs signed rank test.
This trial is ongoing. Results: Data on PK was available for n�8 subjects
(male�4, female�4, median age�62 years). In plasma samples, mean
Cmax (maximum concentration), tmax (time to reach max. concentration),
AUC (area under the plasma-concentration time curve), t1/2 (elimination
half-life) and Cl/F (apparent total clearance) were 350 ng/mL, 101 min,
71.1 min*�g/mL, 103 min and 5903 mL/min. The corresponding parameters
in PBMCs were 558 ng/mL, 97.5 min, 208.4 min*�g/mL, 286 min
and 2475 mL/min, respectively.The AUC plasma/PBMC ratio was 2.93,
indicating accumulation of V in PBMCs. Differences in AUC (p�.008) and
t1/2 (p�.01) reached statistical significance. Conclusions: Interestingly,
significantly higher concentrations of V were achieved in PBMCs andelimination
half-life was prolonged compared to plasma. These results suggest
potent intracellular activity of V.
10043 General Poster Session (Board #47D), Sun, 8:00 AM-12:00 PM
Clinical activity of mTOR inhibition in combination with cyclophosphamide
in the treatment of recurrent nonresectable chondrosarcomas. Presenting
Author: Ofer Merimsky, Sourasky Medical Center, Tel Aviv, Israel
Background: Chondrosarcomas (CS) represent a heterogeneous group of
rare sarcomas, poorly responsive to chemotherapy or radiotherapy. When
local therapies in recurrent or metastatic disease are exhausted, chemotherapy
plays a marginal role. Different molecular pathways have been
shown to be activated in CS. In this retrospective study we summarize our
experience in treating a cohort of patients with recurrent nonresectable CS
with a combination of sirolimus and cyclophosphamide. Methods: Nine
consecutive patients with nonresectable CS were offered off-label treatment
with sirolimus and cyclophosphamide between 2007-2011. Tumor
response, progression-free survival (PFS), adverse events and other relevant
clinical data were analyzed. Results: The median patients’ age was 52
(range, 35-68). Median disease-free interval (DFI) since the primary
diagnosis was 24 months. Median time from the disease recurrence to
initiation of sirolimus and cyclophosphamide treatment was 20.9 months
due to additional local surgical treatments/excision of metastases/slow and
asymptomatic progression. One (11%) objective response was observed
and five (56%) patients had stabilization of disease for at least 6 months.
One patient has been treated for only 3.5 months and reported symptomatic
improvement at this stage, two patients had progressive disease.
Median time to treatment failure (TTF) was 15 months (range, 2.8-30.3).
No significant adverse events were observed. Conclusions: Although advanced
CS remains an incurable disease, our experience suggests that a
combination of sirolimus and cyclophosphamide is well-tolerated and has
meaningful clinical activity with clinical benefit rate of 67%. Further
prospective studies are warranted.
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