APPENDICES - NIHR Health Technology Assessment Programme

192
Appendix 13
Study details Population details Treatment details Results Interpretation
Authors’ conclusions PDT
with MAL–PDT is an excellent
treatment option, particularly for
patients with widespread damage
or AK lesions in cosmetically
sensitive areas
Brief study appraisal
Generally a well-conducted
and reported study; although
the conclusions appear likely to
be reliable, it should be noted
that cryotherapy was delivered
using ‘locally accepted regimens’
allowing clinical variation
between the nine centres
Morbidity Lesion response rate was significantly
higher (91%, 267/295) in the MAL–PDT group,
than the placebo-PDT group (30%, 18/61) and
the cryotherapy group (68%, 278/407), p < 0.001
for both. Response rates were higher in the thin
lesions than the moderately thick lesions with
MAL–PDT; in the cryotherapy group, response
rates were higher for thicker lesions
QoL and return to normal activity A
significantly higher proportion of MAL–PDT
patients graded overall cosmetic outcome as
excellent than with cryotherapy patients (83%
vs 51% as assessed by investigator, p < 0.001; 76%
vs 56% as assessed by the patient, p = 0.013).
Hypopigmentation was present in 5% MAL–
PDT treated sites vs 29% cryotherapy sites.
Hyperpigmentation, scar formation or tissue
defects were present in less than 6% of total
lesion sites. MAL–PDT patient satisfaction was
rated better than previous treatment in 61%,
equal in 24% and worse in 15%. Placebo-PDT
patient satisfaction was rated better than previous
treatment (cryotherapy, surgery or 5-FU) in 21%,
equal in 14% and worse in 64%
AEs No systemic AEs were reported. The most
common AEs were local reactions (74%). 73%
patients experienced at least 1 local AE after
the 1st PDT session and 66% after the 2nd PDT
session; 35% after cryotherapy; 30% after the 1st
and 27% after the 2nd placebo PDT. Most of the
AEs in the MAL–PDT group were mild (48%) or
moderate (40%) intensity. Other reported AEs
common with MAL–PDT were: burning sensation,
stinging, painful skin (46%), erythema (23.9%),
oedema (8.5%), skin peeling (5.1%), blisters (3.4%),
itching (5.1%) and crusting (2.3%). Median duration
was 1 wk or less (all events). 1 MAL–PDT patient
discontinued due to the burning sensation
Trial treatments MAL–PDT vs PDT
with placebo cream vs conventional
cryotherapy
Intervention MAL–PDT: Scales
and crusts were removed and lesion
surface roughened with a curette. MAL
cream (160 mg/g) was applied (1 mm
thickness) under occlusion for 3 hr
then PDT with red light (570–670 nm),
intensities of 50–250 mW/cm2 , total
dose 75 J/cm2 . 2 identical lamps
(Curelight, Photocure ASA, Oslo)
illuminated fields with maximum 5.5cm
diameter, mean exposure time 10 min
with a maximum of six treatment
sites (mapped with acetate sheets and
AKs marked) per patient. Anatomical
landmarks and polaroid photography
also used. This PDT procedure was
repeated after 7 d
Comparator PDT with placebo:
As for MAL–PDT but with colourmatched
cream base instead of MAL
2nd comparator Cryotherapy: AKs
were outlined and lesions were frozen
uniformly with a 1- to 2-mm rim. The
locally accepted regimen was used, i.e.
the protocol specified a single-timed
freeze–thaw cycle with no exact freeze
time (the time from formation of an
ice ball to commencement of thawing).
Lesions with a mean diameter less
than 10 mm had a mean (SD) freeze
time of 0.12 s (0.13); 10- to 20-mm
lesions 0.16 s (0.15) and more than 20mm
lesions 0.26 s (0.11)
Treatment intention
Curative
Type(s) of lesion and
histology Mild to moderate
non-pigmented AK
Main eligibility criteria
Patients with mild to
moderate non-pigmented AK
of the face or scalp suitable
for cryotherapy (with the
largest diameter of each lesion
at least 5 mm)
Patient characteristics
% Male: 56 active PDT; 70
placebo PDT; 61 cryotherapy
Mean age: 64
Age range: 33–89 yr
Cancer stage:
Grade I: 209 active PDT; 35
placebo PDT; 232 cryotherapy
Grade II: 151 active PDT; 39
placebo PDT; 45 cryotherapy.
All patients were Caucasian,
most had Fitzpatrick skin type
I or II
Concomitant treatment
Not stated
Authors
Freeman (2003) 45
Linked
publications164,165 Data source Full
published paper
Country
Australia
Language English
Study design
RCT
No. of
participants
Total: 204
Intervention: 88
(360 AKs) (active
PDT)
Comparator: 23
(74 AKs) (placebo
PDT)
2nd Comparator:
89 (421 AKs)
(cryotherapy)
No. of
recruiting
centres Nine
Follow-up
period and
frequency FU of
3 mth (after a runin
period of up to
2 wk)
s, second(s).