195
Combined Treatment
4.2 Combined treatments: double and triple treat-
ments
Most combined treatments include PDT, with or
without reduction of the standard dose of 50 Joules/
600mWatts/cm², associated to an anti-VEGF agent.
PDT, antiangiogenic agents and steroids are often used
in triple treatments.
According to the US National Institute of Health Clin-
ical Trials Registry, at least 17 studies using combined
treatments are currently in course.
Some of these studies should be referred for their rel-
evance, albeit in a summarized manner.
4.2.1 SUMMIT programme
This programme includes three large randomized clini-
cal trials -
DENALI (USA), MONT BLANC (Europe)
and
EVEREST (Asia)
– whose objective is to evaluate
the efficacy and safety of combining PDT (Visudyne
®
)
and ranibizumab, compared to monotherapy with this
antiangiogenic agent, in patients with neovascular
AMD and polypoidal disease (Everest). Primary analy-
sis results from the Mont Blanc study at twelve months
have shown no significant differences between the two
groups.
4.2.2 RADICAL study
(23)
This is a Phase II, multicenter, randomized study,
using double and triple treatments, with
ranibizumab
(Lucentis
®
), PDT (Visudyne
®
) and dexamethasone
,
compared to monotherapy with Lucentis
®
. Results
analysis at 12 months was positive for the four study
groups. The best outcomes with the smaller number of
treatment sessions were observed for the triple treat-
ment group with half the fluence.
4.2.3 LuceDex study
(24)
This study researches the role of dexamethasone in
neovascular AMD treatment. This is a prospective, ran-
domized clinical trial comparing two treatment groups,
one treated with a combination of
ranibizumab
and
dexamethasone
and the other undergoing ranibi-
zumab monotherapy.
4.2.4 PDEX II study
(25)
This is a prospective, multicentric, randomized, non-
inferiority study comparing the relative advantages of
treatment with
PDT in a reduced dose (reduced flu-
ence), dexamethasone and ranibizumab
versus mono-
therapy with ranibizumab.
4.2.5 CABERNET study
(26)
The objective of this study is to evaluate the efficacy of
epiretinal brachytherapy with strontium 90 combined
with two doses of Lucentis® administered one month
apart, the first being injected upon vitrectomy.
4.2.6 VIA study
(7)
.
The objective of this study is to determine whether a
combination of a reduced dose of PDT and bevacizumab
leads to a decrease in the number of treatment sessions
required within a 6-month period, compared to mono-
therapy with bevacizumab.
This randomized, double-blind, controlled clinical trial
revealed that a combination of bevacizumab and 25-J/
cm² or 12-J/cm² PDT led to a decrease of approximately
50% in the number of treatment sessions required
within a 6-month period. Favourable outcomes were
also observed for visual acuity, although evaluation of
this parameter was not the main objective of this study.
4.3 Considerations
The
FOCUS
study was one of the first multicentric
studies performed using combined treatment with PDT
(Visudyne
®
) and ranibizumab (Lucentis
®
), comparing its
therapeutic efficacy with that of PDT monotherapy. This
study’s shortcoming was failing to compare the efficacy
of combined treatment with that of monotherapy with
the antiangiogenic agent
(27)
.
Although it is a not correct practice to compare results of
two different studies, visual outcomes in this study (con-
sidering the combined treatment arm) were inferior to
the outcomes observed for monotherapy with the anti-
angiogenic agent in the ANCHOR study.
Most combined treatment studies performed were either
non-controlled studies or only monotherapy with PDT
was used in the control group. This is the case of the
FOCUS study.
An important question is to determine whether combin-
ing anti-VEGF agents with PDT results in a real increase
in treatment efficacy regarding the primary endpoint,
visual acuity, in addition to reducing the number of
retreatment sessions required to stabilize vision.
