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Halifax,
N.S--The immune response modifier imiquimod may be useful in
treating basal cell carcinoma, squamous cells, actinic keratoses
and Bowen's disease," Daniel Sauder, MD, said at the annual
CDA meeting.
Because imiquimod downregulates the Th2 cytokines of the immune
system, it is very effective against atopic dermatitis, and has
applications for asthma, allergic rhinitis, and possibly antibody
immediate diseases.
"It also increases antigen presentation, so this is something
you would want to use in situations where you want to augment the
immune system, such as skin cancer, or viral diseases," said
Dr. Sauder, chair, department of dermatology, Johns Hopkins University,
Baltimore, MA.
Basal
cell carcinoma
There is a rational, scientific basis for imiquimod as an anti-tumour
medication for BCC, Amit Pandya, MD, associate professor dermatology,
University of Texas Southwestern Medical Center, Dallas. "We
know that skin cancers are destroyed by a cellular immune response.
. . Biologic response modifiers have anti-tumour properties, and
imiquimod may have a future role," Dr. Pandya said.
"Imiquimod is usually applied for eight hours overnight, it
produces interferon for 24 hours, and the efficacy lasts for many,
days, which is one of the reasons there is a lower relapse rate
when applied to HPV. It has potential activity in certain mouse
cancer models, and indeed it has even shown an ability to keep the
animal from developing the carcinomas such as bladder cancer."
He added that after animals have been injected with imiquimod, they
show long-term anti-tumour effects.
"We still don't know completely yet, but the studies are coming
out in the treatment of nodular and superficial BCCs, as well as
Bowen's disease and actinic keratoses."
A U.S. study presented at this year's AAD meeting showed a confirmed
efficacy in superficial BCC, with complete tumour clearance rates
of 81 to 87 per cent with daily or five-times-a-week-dosing for
12 weeks, and 52 per cent clearance rates for three-times-a-week
dosing. Adverse events were, for the most part, mild to moderate.
An Australian study published in the Journal of the American
Academy of Dermatology, 2001 (44: 807-13) showed an 88 per cent
clearance rate of superficial BCCs with daily application, and 70
per cent clearance with three-times-per-week dosing for only six
weeks.
For nodular BCC, the use of imiquimod has been associated with lower
efficacy. A recent U.S. study showed a 76 per cent clearance rate
on a daily application, and 70 per cent clearance rate on a five-times-a-week
application, for 12 weeks, said Dr. Pandya. "At this point,
it doesn't approach the 90 per cent clearance rate for nodular BCC
seen with surgical therapies, however if you want to treat nodular
BCC, you probably have to continue imiquimod application for up
to 16 weeks, using it five to seven times a week."
Regarding Bowen's disease, Dr. Pandya said an Australian study showed
14 out of 15 patients had no residual tumour after treatment with
imiquimod. "This is very encouraging, because when you have
a large Bowen's disease, you are not keen on doing an excision.
Fortunately, in these patients who were treated relatively aggressively,
they were able to clear 93 per cent of these patients with Bowen's
disease." He noted that there may be irritation of actinic
keratoses around the lesion, or an infection, in which case the
patient should stop application for one week.
Contraindications
There are dermatologic conditions for which imiquimod should not
be used, cautioned Dr. Pandya. "We know that certain diseases
already have a TH1 profile, such as psoriasis, contact dermatitis,
and perhaps biologic response modifiers that augment TH1 should
not be used in these diseases," Dr. Pandya said.
Dr. Sauder said that injecting cytokines is not an optimal way for
dermatologic delivery. "So imiquimod, which is a potent interferon
alpha-inducer among other cytokines, may be very effective in situations
where you want to augment alpha-interferon. In addition to augmenting
alpha-interferon, it also turns to other cytokines - tumour necrosis
factor and interleukin-6, and these are important in immune function."
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