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

10036 General Poster Session (Board #46E), Sun, 8:00 AM-12:00 PM
Phase Ib/II study of INNO-206 (EMCH-doxorubicin) in patients with soft
tissue sarcoma. Presenting Author: Sant P. Chawla, Sarcoma Oncology
Center, Santa Monica, CA
Background: The safety and preliminary tumor response of a doxorubicin
conjugate, INNO-206, was evaluated primarily in patients with metastatic
STS who progressed on prior chemotherpy. INNO-206 consists of doxorubicin
attached to an acid-sensitive linker that binds covalently to cysteine-34
in circulating albumin. Methods: INNO-206 was administered IV at doses of
either 230, 350 and 450 mg/m2 (165, 260 and 325 mg/m2 dox. eq.) every
21 days for up to 8 consecutive cycles. Subsequent dose levels were
administered if � 2/5 or 4/8 patients experienced a non-hematological
dose-limiting toxicity during Cycle 1. Tumor response was monitored every
other month and treatment continued until tumor progression or unacceptable
toxicity. Standard safety monitoring was performed and cardiac
function was followed periodically using MUGA or cardiac ultrasound.
Results: As of January 11, 2012, 25 patients were entered in the study.
21/25 patients had STS of various types. Of the 5 patients treated at 230
mg/m2 INNO-206, 1 subject had grade 3 fatigue and acid reflux. Of the
initial 5 patients entered at the 350 mg/m2 dose, no individuals experienced
a grade 3 or 4 non-hematological toxicity during cycle 1. 2 patients
treated at the 450 mg/m2 dose developed grade 3 oral mucositis during
cycle 1. No patient exhibited cardiotoxicity as determined by MUGA or
cardiac ultrasound. The MTD was determined to be 350 mg/m2 INNO-206
(260 mg/m2 dox.eq.). 15 more patients were entered at this dose (total of
20 patients). Of the 16 patients with STS, 3 objective partial responses
(one of whom received prior doxorubicin) are ongoing as well as 10 patients
with stable disease (range 2-7 months). 1 patient had progressive disease
at the first evaluation. 2 patients died within the first cycle, one due to
progressive disease and the other due to sepsis. Conclusions: INNO-206 is
an active drug for the treatment of patients with advanced STS who have
failed prior chemotherapy. Cumulative doses of 2000 mg/m2 of doxorubicin
equivalents have been achieved, which is over 3 1/2 x the peak
cumulative dose of standard doxorubicin. Adverse events are primarily
hematological and no cardiotoxicity has been observed.
10038 General Poster Session (Board #46G), Sun, 8:00 AM-12:00 PM
A retrospective study from the Royal Marsden Hospital (RMH) of patients
with malignant perivascular epithelioid cell tumors (PEComa) receiving
treatment with sirolimus (SI) or temsirolimus (TSI). Presenting Author:
Joanna Vitfell Pedersen, Sarcoma Unit, The Royal Marsden Hospital,
London, United Kingdom
Background: Perivascular epithelioid cell tumors (PEComas) are rare tumors
driven by tuberous sclerosis complex gene mutations causing upregulation
of mTOR. Two studies reporting a total of five patients (pts) have described
the treatment of PEComa by mTOR inhibition. We report the outcome of 7
pts with PEComa treated with SI or TSI at RMH. Methods: A retrospective
analysis was performed on all pts with PEComa referred to the Sarcoma unit
at RMH between 2000 and 2011. Data collected included gender,
performance status, site of primary tumour, tumour size, surgery, SI/TSI
and SI/TSI dose, toxicity according to common toxicity criteria (CTC)
version 2.0 and response by RECIST. Results: Five (71%) pts were female,
median age was 46 years. Two (29%) had metastatic disease at baseline.
Most common primary site was the gastrointestinal tract (29%). Six pts
received SI, one TSI. Median treatment duration was 131 days (7-1135).
TSI was given at 25 mg IV weekly. Median starting dose of SI was 3 mg daily
(1-4), median highest dose was 4 mg daily (1-5). Best responses by
computed tomography (CT) scan by RECIST criteria were partial response:
3 (43%), stable disease: 2 (29%) and progressive disease (PD): 1 (14%).
One pt only received 7 days of SI and was therefore not evaluable. Two pts
continue on treatment, 3 stopped due to PD, one stopped due to grade (gr)
3 thrombocytopenia and one due to gr 3 cough, but two weeks later had
confirmed PD on CT. Other toxicities reported were generally mild (gr 1/2)
and included mucositis (n:3), rash (n:2), fatigue (n:1), anaemia (n:1),
tooth pain (n:1) and oedema (n:1). One pt experienced a grade 3 trigeminal
nerve pain leading to dose reduction in SI. Therapeutic drug monitoring was
not performed. Conclusions: Our study confirms that SI and TSI are well
tolerated with good clinical response and supports the continuous administration
of SI or TSI for PEComas. A median treatment time of only 131 days
indicates that most pts have a good response to treatment, but responses
are sometimes short-lived and further treatment options are needed,
justifying further research into inhibitors of this signalling pathway.
Sarcoma
639s
10037 General Poster Session (Board #46F), Sun, 8:00 AM-12:00 PM
Analysis of a neoadjuvant regimen with a fixed dose of doxorubicin followed
by a 10-day course of 27 Gy radiation in the treatment of soft tissue
sarcoma (STS) of the extremity/trunk. Presenting Author: John Mathews,
Scott and White Memorial Hospital, Temple, TX
Background: Local tumor control and preservation of limb function are
major goals of treatment of STS. With current standard of combining
limb-sparing surgery and 5-6 weeks of neoadjuvant or adjuvant 50-65 Gy
radiation, reducing local recurrence has been a challenge with rates of
15-30%. Eilber et al. (Cancer Treatment Symposia 1985; 3:49-57) used a
fixed daily dose of doxorubicin for three days with radiation of 35Gy. This
yielded a 5% local recurrence, while wound complication rate was 35 %.
We reduced the radiation dose to lower the wound complications rate. We
report a cohort of patients treated in this manner at our institution.
Methods: After a baseline echocardiogram, patients received a radiosensitizing
dose of intravenous doxorubicin (30mg/day) for 3 consecutive days,
then radiation with 2.7 Gy in 10 fractions, followed by limb sparing surgery.
After IRB approval, we retrospectively analyzed records of 191 patients
during the treatment period from 1991 to 2010. Data extracted included
local tumor recurrences and wound complications defined as non-healed
wound at 1 month, number of limb salvage surgeries and involvement of
surgical margins. Results: Of the 191 patients, median age was 53 (range,
13-89). Stages at presentation included I, II, III and IV, with 2%, 33%,
61%, 4% respectively. The median follow up was 5 years. Of the 24 types
of sarcomas treated, pleomorphic sarcoma was the most common at 21%.
The local recurrence rate was 5% (95% CI, 2.7-8.6%) and local wound
complications were 21% (95% CI, 15-28%). Most (172 or 90%) of
patients were able to undergo limb salvage surgery while 19 (10%) required
amputation. Of the 172 patients that had limb salvage, 97% (95% CI,
93-98%) had wide surgical margins, three had � 2 cm margins and two
had involved margins. Conclusions: To our knowledge, this is the largest
study showing that this short two week course of chemoradiation is
effective in achieving high rate of local control, acceptable wound complication
rate, wide surgical margins and limb salvage in the treatment of STS.
Randomized trials are warranted to confirm results.
10039 General Poster Session (Board #46H), Sun, 8:00 AM-12:00 PM
Palliative ambulatory 14-day infusional ifosfamide in the outpatient setting
for treatment of advanced soft tissue sarcomas (STS): “Old wine in a new
bottle.” Presenting Author: Salma Moona Alam, Sarcoma Unit,The Royal
Marsden Hospital NHS Foundation Trust, London, United Kingdom
Background: Ifosfamide (IFO) has recognised activity in soft tissue sarcomas.
There is evidence for improved cytotoxicity and tolerability utilising a
prolonged 14 day infusional outpatient regimen compared with the
standard 3-day regimen (Loeffler et al 1990). We undertook a retrospective
review of all patients treated with this regimen from September 2008 -
December 2011 to determine toxicity and treatment response. Methods:
Pts. were identified from our database and demographics, histological
subtype, toxicity and survival outcomes were collected. IFO was given via
central venous access using 2x7daypumps at 1g/m2/day with mesna for
14 days q 4 weekly. Oral sodium bicarbonate was used to maintain alkaline
urine with oral mesna for haematuria, and thiamine for symptoms of
encephalopathy as required. Results: 29 patients (pts), with advanced
sarcoma, median age 56 years (27-76 yrs), 14F 15 M, median number of
cycles � 1 ( 1-9). At baseline: PS 0�1, 1�24, 2�4. 18 pts had
de-differentiated liposarcoma (D-LPS), 6 synovial sarcoma, 5 had other
subtypes. 12 pts received only 1 cycle, with 5 stopping due to encephalopathy.
Ten patients developed encephalopathy, 9 occurring in cycle 1, other
toxicity was tolerable, with Gr 2-3 nausea (15 pts) and vomiting (9pts) and
only 2 Gr 3 episodes of myelotoxicity for all cycles. 4 patients achieved PR,
(2 with D-LPS and 2 with Synovial sarcoma) 11 pts. had SD. Median PFS
was 19 months and OS was 12.5 months. 2 pts. with D-LPS had a
sustained prolonged response of 15 and 16 months. Conclusions: Infusional
IFO is generally well tolerated; however a significant incidence of
neurotoxicity was seen. Pts. with D-LPS demonstrated best response to
treatment, a sarcoma subtype that has previously failed to respond to
systemic therapy. This regime warrants further investigation.
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