APPENDICES - NIHR Health Technology Assessment Programme

DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
Study details Population details Treatment details Results Interpretation
Authors’
conclusions The
excellent shortand
long-term
cosmetic results,
low recurrence
rate and high rate
of patient and
physician satisfaction
associated with
ALA–PDT indicate
definite advantages
over other existing
treatment modalities
for AK
Brief study
appraisal Few
methodological
details were reported,
and details of the
study population
were unclear.
The sources of
information appeared
contradictory in
reporting that FU
both ceased at
12 mth, and also
continued for 4 yr.
The 4-yr results were
presented for just
four patients and
this, coupled with
the lack of a clinically
relevant comparison
treatment, further
questions the
reliability of the
authors’ conclusions.
(Attempts were made
to contact authors
for further details.)
Morbidity
At wk 8, CR rate (100%), by no. of patients:
ALA-018: 60/87 (69%) ALA–PDT vs 4/29 (14%) placebo
ALA-019: 59/93 (63%) ALA–PDT vs 4/32 (13%) placebo
At wk 8, > 75% clearance rate, by no. of patients:
ALA-018: 68/87 (78%) ALA–PDT vs 6/29 (21%) placebo
ALA-019: 71/93(76%) ALA–PDT vs 8/32 (25%) placebo
When results for the two trials were pooled, the CR rate, for
number of lesions, was:
Lesion grade I: 666/756 (88%) ALA–PDT vs 122/302 (40%)
placebo
Lesion grade II: 495/632 (78%) ALA–PDT vs 52/199 (26%)
placebo
34% of patients were re-treated at 8 wk
At wk 12 CR rate was 129/180 (72%) in the ALA–PDT group
vs 7/61(11%) in placebo treated patients. A response rate of
least 75% was reported in 158/180 (88%) of ALA–PDT patients
vs 12/61(20%) placebo-treated patients. The clearance rate was
higher for facial lesions than scalp lesions
At 4 yr after PDT, of 32 lesions in four patients (PDT group),
69% (22) remained cleared, 9% (3) were ‘recurrent’ and 22% (7)
were ‘uncertain’. Further results were reported
QoL and return to normal activity For ALA–PDT cosmetic
response was rated as ‘good’ to ‘excellent’ by investigators in
92% of lesions; patients rated cosmetic response as ‘good’ to
‘excellent’ in 94% AK lesions; 85% of patients previously treated
with 5-FU or cryotherapy indicated a preference for ALA–PDT
for future management
AEs Severe stinging and/or burning was reported by at least
50% of PDT patients; less than 3% stopped treatment. In 99%
of PDT patients, some or all lesions were erythematous shortly
after treatment vs 79% in the placebo group. In 35% of PDT
patients some or all lesions were oedematous vs 0% in the
placebo group. Both types of AE resolved or improved by 4 wk.
More ALA patients also reported postPDT itching (26% vs 7%)
Seven patients had an SAE – all were deemed remotely, or not
related to, treatment
Trial treatments ALA–PDT
vs PDT with placebo cream
Intervention ALA–PDT:
Topical 20% ALA and 10 J/cm2 of visible blue light (from
the BLU-U illuminator, for
1000 s) were applied. Lesions
that had not cleared were
re-treated at 8 wk and all
patients were re-evaluated at
12 wk. After 12-wk long-term
lesion recurrence was based
on complete chart review
(including lesion photographs
and treatment during most
recent patient visits at wk
36–48)
Comparator Not described
Treatment intention
Curative
Type(s) of lesion and
histology AK
Main eligibility
criteria Patients with
4–15 grade I or II AKs
on the face or scalp.
Excluded patients had
a history of cutaneous
photosensitisation,
porphyria, hypersensitivity
to porphyrins,
photodermatosis or
inherited or acquired
coagulation defects
Patient characteristics
% Male: 90
Age range: 34–89 yr
The number of treated
lesions per patient ranged
from 4 to 15
Treated areas were the
face or scalp, but not both
in the same patient
Concomitant
treatment Not stated
Authors Fowler and Zax
(2002) 44
Linked publications162,163 Data source Full published
paper. A summary of results
of 2 trials with identical
treatment protocols. Results
for most outcomes were only
available as combined data.
Further data were obtained
from drugs.com162 Country Not stated
Language English
Study design RCT
No. of participants
Total: Reported as being 243,
across two trials – 116 in
trial ALA-018, and 125 in trial
ALA-019 (which totals 241)
Intervention: ALA-018: 87
ALA-019: 93
Comparator: ALA-018: 29
ALA-019: 32
No. of recruiting centres
Multicentre
Follow-up period and
frequency 1, 4, 8, and 12
wk, then FU at intervals of
approximately 3 to 6 mth, up
to 48 mth
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