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

9000 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
Randomized trial of vitamin D3 to prevent worsening of musculoskeletal
symptoms and fatigue in women with breast cancer starting adjuvant
letrozole: The VITAL trial. Presenting Author: Qamar J. Khan, University of
Kansas Medical Center, Kansas City, KS
Background: Musculoskeletal (MS) pain and fatigue are common in women
on adjuvant Aromatase Inhibitors (AIs) and lead to reduced compliance.
Pilot studies suggest a positive impact of vit D on MS pain and disability
from AIs. We conducted a bi-institutional, double blind, placebo controlled
randomized trial to study the impact of 30,000 I.U of vit D3 in preventing
worsening of MS pain and fatigue in women starting letrozole. Methods:
Women with stage I-III breast cancer starting adjuvant AI and a 25(OH)D
level of 40 ng/ml or less were eligible. Women with prior renal stones or
hypercalcemia were excluded. All subjects received letrozole, plus standard
dose vitD3 (600 IU) and calcium (1200 mg) daily, all provided by the
study. Women were randomly assigned to 30,000 IU of oral vitD3 wkly (vitD
arm) or matched placebos (PL arm) for 24 weeks. The following were
assessed at baseline, 12 wks, and 24 wks (end of study): 1) 25OHD levels,
2) symptoms tools (BFI – Brief Fatigue Inventory, HAQII - Health Assessment
Questionnaire II, Qualitative Joint Pain (none, mild, moderate,
severe), BPI – Brief Pain Inventory) and 3) hand grip strength with a
dynamometer. Results: 160 women (80/arm) were enrolled from 4/09 to
7/10. There were no differences between the two arms in demographics/
tumor characteristics. Median age was 61, median BMI was 29.8 kg/m2.
43% had adjuvant chemotherapy. Median 25OHD (ng/ml) was 25 at
baseline, 32 at 12 wks and 31 at 24 wks in the PL arm and 22, 53 and 57
in vitD arm. One patient in the PL arm developed mild hypercalcemia.
There were no SAEs. 147 subjects were evaluable for efficacy. 3 subjects,
all in the PL arm discontinued early due to a MS adverse event. At wk 24, a
higher proportion of women in PL (51%) vs vitD arm (37%) had a protocol
defined MS event (worsening of joint pain, disability from joint pain or
discontinuation of Letrozole due to MS symptoms) (p�0.069). A significantly
higher proportion of women in PL (72%) vs vitD arm (42%) had an
adverse QOL event (worsening of pain, disability or fatigue) (p��0.001).
Conclusions: 30,000 IU/week of vitamin D3 is safe and results in decreased
adverse QOL events from adjuvant aromatase inhibitors in women with
breast cancer.
9002 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
Dexamethasone (DM) for cancer-related fatigue: A double-blinded, randomized,
placebo-controlled trial. Presenting Author: Sriram Yennurajalingam,
University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Cancer-related-fatigue (CRF) is the most common and distressing
symptoms in patients with advanced cancer. Currently, there is no
standard treatment for CRF. Although corticosteroids have been used in the
treatment of CRF, there are no well-powered placebo-controlled trials that
used a validated CRF outcome measure. The primary objective of this
prospective, randomized, double-blind, placebo-controlled study is to
compare the effect of DM versus placebo on CRF. Methods: Advanced
cancer patients with fatigue � 4/10 on the Edmonton Symptom Assessment
Scale (ESAS) and at least 2 other CRF-related symptoms (pain,
nausea, appetite, depression, anxiety or sleep disturbance � 4/10), normal
cognition, no infections and hemoglobin � 9 g/L were eligible for
enrollment. Patients were randomized to either receive dexamethasone 4
mg orally twice a day for 15 days (primary end point) or matching placebo.
The primary outcome was the day 15 change in Functional Assessment of
Chronic Illness-Fatigue (FACIT-F) subscale scores. Differences in the group
means (normal distribution) were analyzed using the two-sample t-test.
Results: In 83 evaluable patients (43 DM and 40 placebo), median age was
60 years, 61% were white, and 53% were female. There was no difference
in the demographics and fatigue (FACIT-F subscale) between DM and
placebo groups except for sex (p�0.02). The mean (SD) FACIT-F subscores
at baseline and at day 15 for DM were 18 (11) and 27 (11) (p�0.001) and
for placebo were 21 (9) and 24 (12) (p�0.06), respectively. Mean
improvement in FACIT-F subscale was significantly higher in the DM group
compared to placebo (9.6 (11) vs. 3.1 (9.7), p�0.005). We found a
significant difference in ESAS physical distress (p�0.02), but no differences
in ESAS overall symptom distress (p�0.11) and ESAS psychological
distress (P�0.88) between DM and placebo. There were insignificantly
higher numbers of grade �3 toxicities in patients who received DM than in
patients who received placebo (20/42 vs. 18/47, p�0.37). Conclusions:
Dexamethasone was more effective than placebo in reducing CRF in
patients with advanced cancer. Long-term safety studies are needed.
Patient and Survivor Care
9001 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
Phase III evaluation of American ginseng (panax quinquefolius) to improve
cancer-related fatigue: NCCTG trial N07C2. Presenting Author: Debra L.
Barton, Mayo Clinic, Rochester, MN
Background: Ginseng is popularly used as a treatment for fatigue, one of the
most common and disabling symptoms in people diagnosed with cancer. It
is termed an “adaptogen”, thought to help the body combat negative
effects of stress. This trial was to evaluate 2,000 mg American Ginseng
versus placebo for cancer-related fatigue (CRF). Methods: Patients with
cancer undergoing or having completed curative intent treatment and
experiencing fatigue, rated at least 4 on a numeric analogue fatigue scale
(1-10) for �1 month, were eligible. Exclusion criteria included CNS
lymphoma, brain malignancies, or prior use of ginseng or chronic systemic
steroids. Other etiologies for fatigue, such as pain and sleep, were also
excluded. Patients were randomized to receive, in a double blind manner,
2,000 mg/d of American Ginseng or placebo in BID dosing for 8 weeks. The
primary endpoint was change from baseline in the general subscale of the
Multidimensional Fatigue Symptom Inventory (MFSI) at 4 weeks. Other
MFSI subscales and the fatigue-inertia subscale of the Profile of Mood
States (POMS) were also analyzed. Data were transformed to a 0-100 scale.
Results: 364 patients were enrolled from 10/2008 to 07/2011. Data at 4
and 8 weeks are provided for several fatigue endpoints in the table below;
higher numbers are better. Mental, emotional and vigor subscales of the
MFSI were not significantly different between arms. There were no
statistically significant differences in any grade of toxicity or self reported
side effects between ginseng and placebo. Conclusions: This trial provides
data to support that American Ginseng reduces general and physical CRF
over 8 weeks without side effects. The treatment did not provide significant
reductions in fatigue at 4 weeks and did not impact mental, emotional, and
vigor dimensions of fatigue.
Fatigue measure Weeks
Change scores (SD)
Ginseng
n�147
567s
Placebo
n�152 p value
MFSI - general 4 14.4 (27.1) 8.2 (24.8) 0.0737
8 20.0 (27.0) 10.3 (26.1) 0.0029
MFSI - physical 4 1.6 (15.9) -0.4 (14.7) 0.3942
8 3.0 (17.9) -1.7 (18.2) 0.0043
MFSI – total 4 4.1 (13.4) 2.1 (12.9) 0.2061
8 6.7 (14.0) 3.7 (14.6) 0.0193
POMS – fatigue/inertia 4 14.5 (25.0) 7.7 (23.6) 0.0795
8 18.6 (24.8) 10.2 (26.1) 0.0083
9003 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
Cluster-randomized trial of early palliative care for patients with metastatic
cancer. Presenting Author: Camilla Zimmermann, Princess Margaret Hospital,
University Health Network, Toronto, ON, Canada
Background: Patients with metastatic cancer have compromised quality of
life (QOL), which tends to worsen towards the end of life. We conducted a
cluster-randomized trial of early versus routine palliative care in patients
with metastatic cancer, to assess impact on QOL, symptom control and
satisfaction with care. Methods: Twenty-four medical oncology clinics were
randomized, stratified by tumour site (4 lung clinics, 8 gastrointestinal, 4
genito-urinary, 6 breast, 2 gynecological), to intervention and follow-up (at
least monthly) by a palliative care team, or to routine cancer care. Eligible
patients had ECOG performance status 0-2 and a clinical prognosis of 6
months to 2 years. Patients completed measures of QOL (FACIT-Sp,
including physical, social, emotional, functional and spiritual well-being;
range 0-156, with higher scores indicating better QOL), symptom severity
(Edmonton Symptom Assessment System; range 0-90, with higher scores
indicating worse symptom severity), and satisfaction with care (FAMCARE-
P16; score range 16-80) at baseline and monthly for 4 months. The
primary outcome was the change in FACIT-Sp at 3 months. The planned
sample size was 225 patients per arm, assuming 80% power and a 2-sided
significance level of 0.05. Results: From December 2006 to September
2010, 461 patients completed baseline measures (228 intervention, 233
control); 442 patients completed at least one follow-up assessment (mean
patients/cluster 18.8�11.6 control, 18.1�12.6 intervention). At 3 months,
patients in the intervention group had marginally improved QOL (mean
change in intervention vs. control, 1.6�14.5 vs. -2.0�13.6, p�0.07) but
not symptom severity (0.1�16.9 vs. 2.1�13.9, p�0.34). At 4 months the
change in QOL was more marked (2.5�15.5 vs. -4.0�14.2, p�0.008)
and symptom severity was marginally better (-1.3�16.0 vs. 3.2�13.9,
p�0.05). Improvement in satisfaction with care was evident at one month
(p�0.001) and remained significant at both 3 months (2.3�9.1 vs.-
1.8�8.2, p�0.001) and 4 months (3.7�8.6 vs. -2.4�8.3, p�0.001).
Conclusions: In patients with metastatic cancer, early palliative care
intervention immediately improved satisfaction with care, while QOL and
symptom control improved later.
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