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

5050 General Poster Session (Board #19B), Sun, 8:00 AM-12:00 PM
Technetium-99m sulfur colloid (TSC) as a phenotypic probe for predicting
pharmacokinetics (PK) and palmar-plantar erythrodysesthesia (PPE) toxicity
of pegylated liposomal doxorubicin (PLD) in patients (pts) with recurrent
epithelial ovarian cancer (EOC). Presenting Author: Hugh Giovinazzo,
University of North Carolina at Chapel Hill, Chapel Hill, NC
Background: There is significant variability in the PK and PD (efficacy and
toxicity) of PLD. Clearance (CL) of PLD has been proposed to occur
primarily via uptake by cells of the mononuclear phagocyte system (MPS)
mainly located in the liver, spleen, and blood. TSC is a radioactive colloid
used clinically for diagnostic and functional imaging of the MPS. Our aim is
to evaluate TSC as a phenotypic probe of MPS activity, which may predict
PLD PK and PPE toxicity in pts (n�9) with EOC. Methods: Prior to
administration of PLD on cycle 1 day 1 (C1D1), TSC was administered at
10 mCi IVP � 1. Dynamic planar and SPECT/CT images of the liver, spleen
and hands were acquired using a gamma camera. Blood samples were
collected up to 60 min after TSC and analyzed for radioactivity using a
gamma counter. On C1D1, PLD was administered at 40 mg/m2 alone or at
30 mg/m2 in combination with carboplatin IV over 1 to 3 h. Serial PK
samples were obtained from 0h to 672h post PLD dose. Plasma was
processed to measure encapsulated and released doxorubicin (dox) using
solid phase separation and HPLC. CL of PLD and TSC were calculated by
non-compartmental analysis. The grade of PPE toxicity was determined by
NCI CTCAE (v4.03) criteria. Results: Nine patients have undergone TSC
imaging and eight patients completed TSC blood PK and PLD plasma PK
studies. There was a positive linear relationship between TSC CL and
encapsulated dox CL (R2 � 0.61, p�0.02). When patients were subdivided,
there was a stronger relationship between TSC CL and encapsulated
dox CL (R2 � 0.81, p�0.03) in pts receiving PLD monotherapy. A positive
relationship using Spearman’s correlation (��0.84, p�0.006) was also
found between maximum grade PPE toxicity developed and estimated AUC
of encapsulated dox in hands [(TSC AUCBlood)/(TSC AUCHand)*Encapsulated Dox AUCPlasma]. Conclusions: These results suggest that TSC is a probe for
MPS function and PLD PK and PD and may be used to individualize PLD
therapy in pts with EOC. In addition, our findings suggest TSC may be able
to predict the development of PPE in patients.
5052 General Poster Session (Board #19D), Sun, 8:00 AM-12:00 PM
Panitumumab and pegylated liposomal doxorubicin in platinum-resistant
epithelial ovarian cancer with KRAS wild-type: The PaLiDo study, a phase II
nonrandomized multicenter study. Presenting Author: Karina Dahl Steffensen,
Department of Clinical Oncology and Radiotherapy, Vejle Hospital,
Vejle, Denmark
Background: Ovarian cancer (OC) patients with platinum-resistant recurrent
disease have few therapeutic options and the response rates are only
10-20% using non-cross-resistant chemotherapeutic agents. The increasing
number of negative trials for OC treatment has prompted an evaluation
of new biologic agents, which in combination with chemotherapy may
result in improvement in survival. Panitumumab is a fully human monoclonal
antibody specific to the epidermal growth factor receptor (EGFR). No
previous studies have evaluated the effect of panitumumab in OC based on
KRAS mutation status. The main purpose was to investigate the response
rate in platinum-resistant, KRAS wild-type OC patients treated with
pegylated liposomal doxorubicin (PLD) supplemented with panitumumab.
Methods: Major eligibility criteria were confirmed stage I-IV primary
epithelial ovarian/fallopian/peritoneal cancer patients with progression
either during or within 6 months after end of first or second line
platinum-based chemotherapy. Only patients with measurable disease by
CA125 criteria and with KRAS wild type were eligible. Patients were treated
with panitumumab 6 mg/kg day 1 and day 15 and with PLD 40 mg/m² day
1, every 4 weeks. Tumor assessment was performed at baseline and at every
third cycle according to CA-125 criteria. Results: A total of 46 patients were
enrolled by 6 study sites in this multi-institutional phase II trial. Within the
population evaluable for response (N�33), there was 8 CA125 responders
for an overall response rate of 24.3 %. Progression-free and overall survival
in the intention-to-treat population (N�43) was 2.7 months (2.5-3.2
months, 95%CI) and 8.1 months (5.6-11.7 months, 95%CI), respectively.
The most common treatment related grade 3 toxicities included skin
toxicity (42%), fatigue (19%) and vomiting (12%). Conclusions: The
combination of PLD and panitumumab demonstrates efficacy in platinum
refractory/resistant patients although the dermatologic toxicity was considerable.
Gynecologic Cancer
339s
5051 General Poster Session (Board #19C), Sun, 8:00 AM-12:00 PM
Sexual function, sexual activity, and quality of life in women with ovarian
and endometrial cancer. Presenting Author: Philipp Harter, Kliniken Essen
Mitte, Essen, Germany
Background: Gynecological cancer (GC) is generally assumed to have an
impact on sexual function and activity. Although there are several studies
addressing the issue, case control studies are currently limited. Methods:
We performed a cross-sectional investigation of sexual function and activity
utilizing the sexual activity questionnaire, the female sexual function
index, and parts of the EORTC QLQ C30. Patients with gynecological
cancer (GC) like ovarian and endometrial cancer were compared with a
control group (C) of non-cancer patients. Inclusion of GC was only allowed if
treatment was completed �12 months previously and patients were
disease-free. Results: The questionnaires were sent out to 727 women (335
x GC and 392 x C), 22.8% of which responded. Response rates in both
groups were equivalent (79 pts with GC [23.6%] and 87 control subjects
[22.2%]). Median age was 57 years (C) and 62 years (GC), respectively
(p�0.237). 51.5% (C) and 59.5% (GC) were not sexually active, mainly
owing to lack of a partner (37%) or lack of interest (21%) in controls and
lack of interest (40%, p�0.05), self-reported physical problems (31.9%,
p�0.05), and physical problems of the partner (21%, p�0.05). There
were significant differences between both groups in the SAQ discomfort
score (p�0.05). We did not observe significant differences in quality of life
or other scores regarding sexuality. Conclusions: About half of the women in
both groups were not sexually active. However, reasons for non-activity
differ. Quality of sexuality tends to be impaired in GC patients, but this
seems not to influence quality of life. A shift of priority caused by
substantial anxiety regarding cancer specific survival might explain our
findings.
5053 General Poster Session (Board #19E), Sun, 8:00 AM-12:00 PM
Effect of tumor-infiltrating T-lymphocytes on the aggressiveness of epithelial
ovarian tumors. Presenting Author: Ines Vasconcelos, Department of
Gynaecology, European Competence Center for Ovarian Cancer, Campus
Virchow Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany
Background: Borderline ovarian tumors (BOT) are a low-grade form of
ovarian malignancy with significantly less aggressive behavior than epithelial
ovarian cancer (EOC). Since there is neither convincing scientific
evidence nor a marker capable of predicting BOT’s behavior, we analyzed
the role of immune tolerance in differential disease outcome. EOC and BOT
were chosen due to similar disease etiology, despite different disease
courses. Increased numbers of T-cell subpopulations infiltrate malignant
tumors, so we used epigenetic tests to determine the prevalence of
regulatory T-cells (Treg) and overall-T-Lymphocytes (oTL) in EOC and BOT.
Methods: The ovarian cancer samples were provided by the European
multicentric OVCAD study. The BOT samples were obtained from Tumor
Bank Ovarian Cancer at Charité Campus Virchow (Germany). Samples and
clinical data were prospectively collected and documented using validated
SOPs. DNA was bisulphite-converted and forwarded to methylationspecific
RT-PCR for CD3 and FOXP3 loci. Results: We evaluated 90
high-grade EOC, 12 BOT with invasive implants and 25 non-invasive BOT
samples. Higher oTL-values correlate with mortality (p�0.008) and recurrence
(p�0.001), while higher Treg levels correlate with recurrence
(p�0.028). Patients with non-invasive BOT have lower oTL (p�0.019) and
Treg (p�0.0005) levels than patients with invasive BOT and EOC, while
BOT (both invasive and non-invasive) patients have lower Treg-to-oTL ratios
than EOC patients (p�0.0005). Finally, oTL levels associate with overall
survival in EOC (p�0.042). Conclusions: We observed a strict correlation
between tumor-type, Treg and oTL levels, as well as Treg-to-oTL ratio. This
is in agreement with our hypothesis that disease aggressiveness is associated
with the amount tumor-infiltrating lymphocytes and may provide the
explanation for differing disease courses in EOC and BOT.
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