News & Analysis
Clinical Trials Update
Mega Ovarian Cancer Screening Trial
Shows Modest Reduction in Mortality
One of the largest ever randomized trials has
concluded that ovarian cancer screening
may reduce ovarian cancer mortality by an
estimated 20% after up to 14 years (Jacobs
IJ et al. Lancet. doi:10.1016/S0140-6736(15)
01224-6 [published online December 17,
2015]). Ovarian cancer has had a poor prog-
nosis for 3 decades; currently, less than 30%
of patients are diagnosed at an early, poten-
tially curable, stage.
The UK Collaborative Trial of Ovarian
Cancer Screening (UKCTOCS) randomly as-
signed 202 638 postmenopausal women in
a 1:1:2 ratio to annual multimodal screening
(MMS) with serum CA125 interpreted with
the risk of ovarian cancer algorithm, rather
than an absolute cutoff, and with transvagi-
nal ultrasound scan (TVS) as a second-line
test (MMS group); annual TVS alone (USS
group); or no screening. The MMS and USS
groups were offered 7 to 11 screens and fol-
lowed up for 14 years from randomization.
At a median follow-up of 11.1 years, ovar-
ian cancers were diagnosed in 0.7% of
women in the MSS group and 0.6% of
women in the USS and no-screening groups.
Only 59% of ovarian cancers were de-
tected by multimodal screening and 51% by
ultrasound alone. According to the primary
outcome of ovarian cancer death by the end
of the trial, there were no significant reduc-
tions in mortality in the MSS and USS groups
(15% and 11%, respectively) relative to no
screening. The relative mortality reduction
was 8% after 7 years of annual screening but
increased to 23% in the 8- to 14-year period
after screening in the MSS group, compa-
rable with that for the USS group (2% in
years 0 to 7 and 21% in years 8 to 14).
An analysis excluding women who had
undiagnosed ovarian cancer when they
joined the trial showed a significant mortal-
ity reduction of 28% in years 8 to 14 after
screening with MMS, providing encourag-
ing evidence for the utility of this screening
approach. The difference in mortality be-
tween women who were screened vs those
who were not seems likely to increase over
time, according to the authors, who sug-
gest additional follow-up of the UKCTOCS
742 JAMA February 23, 2016 Volume 315, Number 8 (Reprinted)
Copyright 2016 American Medical Association. All rights reserved.
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cohort before firm conclusions can be
reached on the efficacy and cost-effective-
ness of ovarian cancer screening.
Antiplatelet Drug Doesnt Reduce Pain
of Sickle Cell Anemia
Children and adolescents with sickle cell ane-
mia who received the adenosine diphospha-
tedirected antiplatelet agent prasugrel had
no significant reduction in painful vasooc-
clusive crises compared with those who re-
ceived placebo, found a trial conducted in
13 countries (Heeney MM et al. N Engl J Med.
doi:10.1056/NEJMoa1512021 [published
online December 8, 2015]). Previous stud-
ies had suggested that prasugrel reduced
markers of platelet activation and, conse-
quently, the rate and intensity of vasoocclu-
sive pain in sickle cell anemia.
In this phase 3 clinical trial, a total of 341
patients aged 2 through 17 years were ran-
domly assigned in a 1:1 ratio to receive oral
prasugrel or placebo for 9 to 24 months. In
the prasugrel group, 67.3% of patients ex-
perienced a vasoocclusive crisis compared
with 72.4% of those in the placebo group.
The primary end point, rate of vasoocclu-
sive crisis events per person-year, was 2.30
in the prasugrel group and 2.77 in the pla-
cebo group. There were no significant dif-
ferences between the groups in rate and in-
tensity of pain or in adverse events.
The ineffectiveness of prasugrel may be
attributed to lower than expected levels of
platelet inhibition, and as such, higher doses
of antiplatelet agents or use in combination
with other drugs may be beneficial, accord-
ing to the authors. In addition, that children
12 years and older in the prasugrel group had
a smaller, but nonsignificant, number of va-
soocclusive crises than younger children sug-
gests platelet activation may be more im-
portant in older patients.
Melatonin to Improve Skin and Sleep
in Pediatric Dermatitis
Atopic dermatitis (AD) is a pruritic chronic in-
flammatory skin disease that affects 15% to
20% of children and is often accompanied
by sleep disturbances. According to find-
ings from a recent randomized trial, mela-
tonin was safe and effective in improving the
A recent trial investigates the benefits of ovarian
cancer screening.
severity of atopic dermatitis (AD) in chil-
dren and adolescents while also reducing
sleep disturbance (Chang YS et al. JAMA
Pediatr. 2016;170[1]:35-42).
Forty-eight children (aged 1-18 years) with
AD and with sleep disturbances (>3/week)
were randomized 1:1 to 2 groups: either mela-
tonin (3 mg/d) or placebo treatment for 4
weeks. After a 2-week washout period, the
melatoningroupreceivedplacebo,andthepla-
cebo group received melatonin for another
4 weeks. Participants continued with their
original treatments for AD during the trial.
Atopic dermatitis severity was evalu-
ated using the Scoring Atopic Dermatitis
(SCORAD) index, and secondary outcomes
included sleep variables. After melatonin
treatment, the SCORAD index decreased by
9.1 points compared with placebo. The sleep-
onset latency was also shortened by 21.4
minutes after melatonin treatment vs pla-
cebo. The improvement in the SCORAD in-
dex did not correlate significantly with the
change in sleep-onset latency, melatonin did
not affect other sleep variables compared
with placebo, and no adverse events were
Steve Gschmeissner/sciencesource.com
reported.
Although the effect was modest, mela-
tonin supplementation has the potential to
improve quality of life for patients and fami-
lies as it simultaneously improves sleep and
may prevent children from scratching and
exacerbating their condition, wrote the re-
searchers. Anita Slomski, MA
jama.com