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

10044 General Poster Session (Board #47E), Sun, 8:00 AM-12:00 PM
High-dose ifosfamide (HDI) in metastatic synovial sarcoma: The Institut
Gustave Roussy experience. Presenting Author: Arslane Skander Rahal,
Institut Gustave Roussy, Villejuif, France
Background: Synovial sarcoma (SS) is one of the most chemo-sensitive
histological subtypes of sarcoma but with a dismal prognosis. In metastatic
setting, Anthracyclin/ifosfamide-containing chemotherapy (CT) regimen is
the gold standard of treatment in front-line therapy. Patients (pts) with
resistant diseases are candidates to investigational drugs or higher dose
ifosfamide regimen in selected pts. Methods: Pts treated in our institution,
with histological confirmation of advanced SS, adequate organ function
and in good condition (PS�2) were included in this retrospective analysis.
Pts who progressed after 1–2 chemotherapy lines received High-dose
ifosfamide (HDI) in the form of 4 g/m2 daily (over 24 hours CI) for 3 days for
a total dose of 12 g/m2 ; cycles were given with growth factor support and
were repeated every 3 weeks. The primary endpoints were PFS and overall
response rate (ORR); the secondary endpoints OS and toxicity profile. AE
were assessed by NCI-CTC v. 3.0. Results: 34 pts (21 males) with a median
age of 39 years (range 19-66) received this HDI regimen. PS was 0-1 in
90%. 95% of pts received prior doxorubicin, ifosfamide or both, 7 patients
had 2 prior lines. Grade III monophasic pattern was seen in 21 patients,
grade II in 13. 171 cycles were delivered, median number of cycles was 4
(2-10). The objective responses were CR 0; PR 15; SD 14; PD 2; and NE 3,
resulting in an ORR of 44%. The clinical benefit rate was 85%. Median
PFS: 11.6 months (95% CI: 9-14). Eleven pts were amenable to a
subsequent resection of residual disease. Common adverse events included
grade III/IV neutropenia: 47%, febrile neutropenia: 12%, thrombocytopenia:
12%, cystitis: 3%, neurologic: 3%. There was no treatment
related death. Conclusions: HDI demonstrated clinically meaningful efficacy
with manageable toxicity in pts who failed previous standard Ifosfamide
dose. Ifosfamide remains the most active agents in SS and high
dose regimen have to be considered in pts previously treated with
ifosfamide.
10046 General Poster Session (Board #47G), Sun, 8:00 AM-12:00 PM
Rechallenge with ifosfamide-containing regimen as salvage option for
patients with metastatic soft tissue sarcomas progressing after multiple
pretreatments. Presenting Author: Mathias Hoiczyk, Sarcoma Center, West
German Cancer Center, Essen, Germany
Background: Ifosfamide (I) is commonly used in first or second-line
treatment of locally advanced or metastatic soft tissue sarcomas (STS). The
clinical efficacy of a rechallenge with ifosfamide (IR) or I-containing
regimen (ICR) is unclear. We conducted a retrospective analysis of our
institutional database (n�1354) of pts who received IR or ICR. Methods:
66 STS pts were identified, who had received more than one I-based
regimen. Ifosfamide retreatment was given in neoadjuvant (n�26), adjuvant
(n�18) or metastatic settings (n�22) and most patient were pretreated
with doxorubicin (D; 94%). PFS was determined from first
administration of IR until disease progression, OS from R until last
follow-up or death. ORR (RECIST) was assessed to determine the clinical
benefit rate (CBR) defined as CR, PR plus SD. Covariates were age, gender,
histology, pretreatment, dose intensity, response and toxicity. Results:
Median age at time of first I was 45y (range: 17-74, 44% f 56% m). Median
time from diagnosis until first ICR treatment was 4mo. Median time from
first I until IR, which was given as median 3rd-line treatment (2-9 lines),
was 17 mo. Histologies were 12 leiomyo-, 11 lipo- 13 pleomorphic,14
synovial, 4 rhabdomyosarcomas and 12 other subtypes. Pts received a
median of I 9.6 g/m²/cycle and a median of 4 cycles. I was given as
monotherapy (38%) or in combination (D: 45%, other 17%). Overall
median PFS was 5mo with PFS-rates of 63% at 12 and 25% at 24 wks.
Median PFS was 6 mo for ICR and 2 mo for IR. The median OS was 36 mo
from time of first diagnosis of metastases or locally advanced disease. ORR
was 29% for I/D combination (CBR 70%) and 12 % for I monotherapy
(CBR: 52%). 22 pts received a second IR with a median of 2 cycles (27%
PR; CBR:77%; 69% combinations). Most common toxicities for IR/ICR
were neutropenia (42%), encephalopathy (21%) and neutropenic fever
(18%). Dose reductions were necessary in 18% of pts and treatment was
stopped in 8% due to toxicity. No significant cardiotoxicity was observed.
Conclusions: Patients with soft tissue sarcomas who had at least disease
stabilization after initial ifosfamide-based therapy may derive substantial
clinical benefit from a rechallenge.
Sarcoma
641s
10045 General Poster Session (Board #47F), Sun, 8:00 AM-12:00 PM
Clinical effectiveness of recombinant adenovirus human p53 gene combined
with hyperthermia in treatment of advanced soft tissue sarcoma.
Presenting Author: Shaowen Xiao, Peking University Cancer Hospital and
Institute, Beijing, China
Background: Soft tissue sarcoma in advanced stage usually resist to both
chemo- and radiotherapy. Several studies indicated that rAdp53 can
reverse this resistance and enhance the effectiveness of radiotherapy,
chemotherapy and hyperthermia. This study is to evaluate the efficacy and
safety of recombinant adenovirus human p53 gene (rAdp53) combined
with hyperthermia and radiation in treatment of advanced soft tissue
sarcoma. Methods: From Nov. 2001 to July 2011, 30 patients with
advanced soft sarcoma were enrolled in this study. All cases received
hyperthermia treatment, once a week for total of 9 times, and intratumoral
injection of rAdp53 at dose of 1x1012 virus particles (vp) for 8 times.
Radiation were given 48 hours after the first rAdp53 injection at a dose of
2Gy/f, five fractions a week for a total dose 16~70Gy /8~35f/2~8w, at an
average of 56.3�5.3 Gy. Patients were monitored for response and adverse
events. Results: The median follow-up time was 96 months. Among these
patients, one case (3.3%) achieved complete response (CR), 9 (30%)
cases had a partial response (PR), and 18 (60.0%) cases had a stable
disease (SD). The overall clinical effectiveness rate (CR�PR�SD
� 6months) was 83.3.0% (25/30). One-year survival rate is 56.6%
(17/30), 2-year survival rate is 23.3% (7/30), 3-year survival rate is 10.0%
(3/30), and 5-year survival rate is 6.7% (2/30). Overall median survival
time was 18.1 months and median TTP was 13 months. No significant
adverse events were noted, except for transient fever associated with
rAdp53 administration. Conclusions: rAdp53 combined with hyperthermia
and radiation is effective and safe modalities in treatment of advanced soft
tissue sarcoma.
10047 General Poster Session (Board #47H), Sun, 8:00 AM-12:00 PM
Association between body weight and efficacy outcomes during trabectedin
therapy for recurrent advanced soft tissue sarcoma (STS). Presenting
Author: Maurizio D’Incalci, Istituto di Ricerche Farmacologiche, Milan,
Italy
Background: Trabectedin is the first marine-derived antineoplastic drug
approved in Europe for the treatment of patients with recurrent advanced
STS. Different studies have implicated tumor-derived cytokines as mediators
of cachexia in cancer patients. Preclinical studies have demonstrated
that trabectedin acts on tumor microenvironment particularly reducing
IL-6, which is involved in cancer-induced cachexia (Germano et al. 2011,
Ligouri et al. 2011). Methods: This exploratory retrospective analysis
evaluated the association between body weight increase during treatment
with respect to baseline and efficacy outcomes in 319 adult patients with
recurrent STS. Patients were treated in four phase II trials with trabectedin
at the approved dose of 1.5 mg/m2 , given as a 24-hour infusion every 3
weeks. An analysis of the concordance between weight increase and
objective response (OR) rate, tumor control (TC) rate (OR�stable disease
lasting �3 months), progression-free survival (PFS) and overall survival
(OS) was performed. Results: Correlation between weight increase and
responses was observed: 68% of patients who achieved OR and 70% of
patients with TC increased their weight for a median of 1.2 kg. Remarkably,
PFS (5.1 vs. 1.9 months; p�0.0001, log rank) and OS (21.0 vs. 8.2
months; p�0.0001, log rank) were significantly prolonged in patients who
gained weight during treatment. Six and 12-months Kaplan-Meier PFS
estimates and survival rates at 12, 24 and 36 months were also better in
those patients. Additionally, in Cycle 1-2, a significant relationship
between weight increase and improved median PFS (4.2 vs. 2.2 months;
p�0.0001) and OS (19.4 vs. 9.3 months; p�0.0002) was observed. This
is in concordance with the tendency to gain weight starting from the first
cycle of treatment. Conclusions: This analysis suggests that weight gain is
associated with favorable efficacy outcomes when patients are treated with
trabectedin. Further research is needed to assess the prognostic value of
weight changes as a complementary source of evaluation on the long-term
clinical outcomes and impact of trabectedin on tumor microenvironment.
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