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

9024 Poster Discussion Session (Board #8), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Phase Ib, multicenter, single-blinded, placebo-controlled, sequential doseescalation
study to assess the safety and tolerability of topically applied
AG013 in subjects with locally advanced head and neck cancer (LAHNC)
receiving induction chemotherapy (ICT). Presenting Author: Sewanti Atul
Limaye, Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA
Background: Oral mucositis (OM) is a significant toxicity of ICT in LAHNC.
AG013, a mouth rinse composed of a recombinant Lactococcus lactis
(sAGX0085) engineered to secrete human Trefoil Factor 1 (hTFF1) and
deficient in the gene encoding thymidylate synthase, was investigated in
patients receiving ICT (cisplatin, 5-fluorouracil �/-docetaxel:PF�/-T).
TFFs have wound-healing properties and are protective of mucosal tissues.
Methods: To evaluate the safety, tolerability, PK profile and efficacy of
AG013 in attenuating ICT-associated OM, 52 patients (pts) with newly
diagnosed LAHNC receiving ICT (24TPF, 1PF) were screened in ICT cycle
(Cy) 1 for symptomatic OM (SOM). 25 pts who developed SOM in Cy1 were
enrolled into 3 successive groups of at least 7 pts each in the active phase
and randomly assigned at the Baseline visit (d1 of ICT Cy2) in a 5:2 ratio to
receive AG013 or placebo during ICT Cy2. Dose was escalated in successive
groups from 1 x/day (qd) to 3 x/day (tid) and to 6 x/day, resulting in
doses of2x1011 ,6x1011 , and 1.2 x 1012 colony-forming units (CFU)/day
respectively. Pts were assessed daily from Cy 2 d1 to d14 for OM using
WHO criteria. Safety endpoints and PK (mucosal, salivary and blood
samples) were assessed. Results: AG013-sAGX0085 could not be detected
in blood. Recovered oral live bacterial levels were high immediately after
dosing, decreased by 90 minutes post dose, and undetectable at study end.
No differences in hTFF1 serum levels were seen. Pts in the placebo group
had ulcerative OM (UOM) on nearly 60% of the days vs. 35-40% days in the
AG013 group. 29 % pts who received AG013 had 0 or 1 day of UOM vs. at
least 2 days of UOM in the placebo group. Pts who received AG013 on any
dosing schedule had a lower % of days with OM, fewer unplanned office and
emergency room visits compared to pts who received placebo. No differences
were noted in mouth and throat soreness, opioid use, or gastrostomy
tube placement. Conclusions: Topical administration of AG013 appears
safe, well tolerated and effective in reducing the severity and course of OM
in patients receiving ICT for HNC.
9026^ Poster Discussion Session (Board #10), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Effect of cancer cachexia on treatment toxicity in metastatic colorectal
cancer patients: Results of a prospective multicenter study. Presenting
Author: Maximilien Barret, Hôpital Européen Georges Pompidou, Department
of Gastroenterology, Paris, France
Background: Malnutrition reduces tolerance to treatment and survival in
numerous cancers, including metastatic colorectal cancer (mCRC). Previous
studies have shown that chemotherapy toxicity may be linked to
sarcopenia. We evaluated the effect of sarcopenia on chemotherapy toxicity
among mCRC patients. Methods: In this prospective, cross-sectional,
multicenter study, oncological and nutritional data were collected in all
consecutive mCRC patients between March 7th and March 20th 2005 in
three hospitals. Computed tomography (CT) images were analysed using
Slice-O-Matic software V4.3 (Tomovision) to evaluate cross-sectional areas
(cm2) of muscle tissue (MT), visceral and subcutaneous adipose tissue
(VAT and SAT). The 3rd lumbar vertebra (L3) was chosen as a reference,
since L3 and whole-body measurements are linearly related. Indexed on
height, MT, VAT and SAT (cm2/m2), were computed and described, after
stratification on sex. In accord with the literature, sarcopenia was defined
as MT �55 cm2/m2 for men and �39 cm2/m2 for women. Images were
obtained within one month of clinical evaluation. Toxicities were evaluated
according to the NCI-CTC, version 3.0, in the two months following clinical
evaluation. Results: 53 mCRC patients (72% men (M)), participated in the
study. According to body mass index (BMI) only 7% of female patients (F)
and 3% M were malnourished (BMI�17 kg/m²), and 93% F and 97% M
were of normal weight or overweight (BMI� 25kg/m²). These results are to
be compared to the 38% (F) and 82% (M) of patients with sarcopenia.
Grade 3-4 toxicities were observed in 28% of the cases, with neurotoxicity
in 6%, diarrhea 2%, anemia 2%, neutropenia 9%, and nausea and
vomiting 6%. In multivariate analysis including age, sex, BMI, sarcopenia,
SAT and VAT, the only factor associated with grade 3-4 toxicity was
sarcopenia (OR� 13.55 95% CI [1.08;169.31], p�0.043). Conclusions:
In mCRC patients undergoing chemotherapy, low muscle tissue was much
more frequently observed (68%) than “visible” malnutrition (4%). Despite
the small number of patients included in our study, we showed that
sarcopenia was associated with severe chemotherapy toxicity in mCRC.
Patient and Survivor Care
573s
9025 Poster Discussion Session (Board #9), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Parenteral hydration (PH) in advanced cancer patients: A multi-center,
double-blind, placebo-controlled randomized trial. Presenting Author:
Shalini Dalal, University of Texas M. D. Anderson Cancer Center, Houston,
TX
Background: The vast majority of cancer patients at the end of life receive
PH in hospitals and no PH in hospice. There is limited evidence supporting
either practice. Our preliminary study suggested that PH (1L/day) improved
dehydration symptoms (Bruera et al. JCO 2005). In this randomized
controlled trial, we determined the effect of PH on symptoms associated
with dehydration, quality of life and survival for patients with advanced
cancer. Methods: We randomly assigned 129 cancer patients from 6
hospices to receive subcutaneous PH (normal saline 1 L/day) or placebo
(normal saline 100 mL/day) daily over 4 hours. The primary outcome was
change in the sum of 4 dehydration symptoms (fatigue, myoclonus,
sedation and hallucinations, 0�best and 40�worst possible) between day
4 and baseline. Secondary outcomes included Edmonton Symptom Assessment
Scale (ESAS), Memorial delirium assessment scale [MDAS], Nursing
delirium screening scale [NuDESC], unified myoclonus rating scale [UMRS],
FACIT-F, creatinine, urea, and overall survival. Intention-to-treat analysis
was conducted to examine the change in each variable between baseline
and day 4 or day 7. Log rank test was used for survival analysis. Results:
Mean age was 67 (range 43-92), female 61%, Caucasians 60%, gastrointestinal,
genitourinary and lung cancers 70%, performance status 3-4 113
(88%), with no baseline differences between the hydration (N�63) and
placebo (N�66) groups. No significant differences were found between the
hydration and placebo groups for the sum of 4 dehydration symptoms (-3.3
v. -2.8, p�0.77), ESAS (all non-significant), MDAS (1 vs. 3.5, p�0.084),
NuDESC (0 v. 0, p�0.13) and UMRS (0 vs. 0, p�0.54). We also did not
identify any group differences for day 7, except for a decrease in urea level
in the hydration group (-2 vs. 2, P�0.02). Median overall survival was 21
days for PH and 15 days for placebo (p�0.83). Conclusions: PH at 1 L/day
did not improve symptoms, quality of life or survival compared to placebo.
Further studies are required to determine if any subgroups would benefit
from PH.
9027 Poster Discussion Session (Board #11), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Curcumin for radiation dermatitis: A randomized, double-blind, placebocontrolled
clinical trial of 30 breast cancer patients. Presenting Author:
Julie L. Ryan, University of Rochester Medical Center, Rochester, NY
Background: Radiation dermatitis occurs in approximately 95% of patients
receiving radiation therapy for cancer and often leads to pain and treatment
delays. There is no standard treatment with demonstrated effectiveness for
the prevention of radiation dermatitis. We conducted a randomized,
double-blind, placebo-control clinical trial to assess the efficacy of curcumin,
a potent antioxidant and anti-inflammatory component of turmeric,
to reduce radiation dermatitis in 30 breast cancer patients. Methods:
Eligible patients included adult females with non-inflammatory breast
cancer or carcinoma in situ prescribed radiation therapy without concurrent
chemotherapy. After randomization, patients took four 500 mg capsules of
curcumin or placebo three times daily throughout their course of radiation
therapy (total daily dose � 6.0 g). Weekly assessments included Radiation
Dermatitis Severity (RDS) Score, presence/absence of moist desquamation,
erythema measure, and McGill Pain and Symptom Inventory (SI)
questionnaires. Results: The 30 evaluable patients were white (90%; mean
age � 58.1 years) with ER�PR� breast cancer (76.7%) who did not have
total mastectomy (90%) or chemotherapy prior to start of radiation therapy
(56.7%). No significant differences were observed between arms for
demographics, compliance, erythema, pain, symptoms, or radiation skin
dose. Standard pooled variances t-test showed that curcumin reduced RDS
at end of treatment compared to placebo (mean RDS � 2.6 vs 3.4;
p�0.008). Fisher’s exact test showed that curcumin significantly reduced
the presence of moist desquamation at the end of radiation therapy (28.6%
vs. 87.5 %; p�0.002). Repeated measures analysis confirmed divergence
of RDS between curcumin and placebo arms at Week 5. Conclusions: Oral
curcumin, 6.0 g daily during radiation therapy, reduced radiation dermatitis
severity and moist desquamation in breast cancer patients. A multisite
CCOP trial (N�700) is underway to confirm the effectiveness of curcumin
to reduce radiation dermatitis severity during various radiation therapy
regimens for breast cancer. Support: IND 75,444, Dermatology Foundation,
KL2 RR024136, NCI PHS 1R25CA10618.
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