AIDS TREATMENT UPDATE, October 1995
Kaposi's sarcoma (KS) is an AIDS-defining illness that affects
a substantial proportion of HIV-positive gay men and Africans.
KS lesions can develop both inside and on the surface of the
body. On the skin they look like brownish-red to purplish-black
KS on the skin is not life-threatening, but visceral KS
(involving the internal organs) can be. KS in the lymph nodes
can obstruct normal fluid drainage leading to the body tissues
to swell up painfully (oedema). KS in the lungs (pulmonary KS)
can obstruct the airways causing a cough and breathlessness,
and increases the risk of chest infections.
Many doctors and people with HIV are unwilling to treat KS that
is restricted to a few skin lesions and causing no problems. If
these are disfiguring, advice on camouflage make-up is
available from many clinics and self-help groups. However, if
you do decide to treat skin lesions, or your KS is severe
enough that treatment is necessary (such as painful lesions on
the soles of the feet), there is a range of options.
INTERFERON & RADIATION
Radiation therapy can be used to treat KS lesions in the mouth
or throat, painful skin lesions or lesions that are causing
blockages in the lymph nodes of the face, arms and legs. The
idea is to kill the over-active tumour cells with a series of
low doses of radiation, leaving the rest of the body untouched.
Side-effects can include short-term reddening of the skin and
hair loss and, in the mouth, inflammation of the mucous
membranes. The lesions usually leave a scar, like a mole, where
pigmentation remains in the skin. This is particularly common
when long-standing lesions are treated.
Interferon has been reported to be a helpful treatment for some
people with KS. The best results have been seen when it is used
by people with early KS, limited to the skin, at relatively
high CD4 counts. Interferon has to be injected and usually
causes side-effects of flu-like symptoms. It can also cause
neutropenia - shortage of white blood cells called neutrophils
which fight infections. This can leave the individual
vulnerable to bacterial infections.
Alternatively, individual skin lesions can be injected with
chemotherapy drugs, which causes the lesion to swell up
painfully but then shrink or disappear, leaving a scar. Other
approaches to treating skin lesions including removing them
surgically or freezing them with liquid nitrogen.
Cytotoxic chemotherapy uses drugs that kill actively
reproducing cells. They are used to treat cancers because
cancerous cells reproduce at a high rate. The aim is to wipe
out many cancerous cells without doing too much damage to
normal, healthy cells.
In practice, chemotherapy tends also to damage the
rapidly-dividing cells of the bone marrow, causing neutropenia.
Some chemotherapy drugs have other unpleasant side-effects,
including hair-loss and nausea.
Cancer doctors try to minimise these effects by selecting drugs
that are least toxic to the bone marrow, including vincristine,
vinblastine and bleomycin. These are used in combination and
cause relatively few side-effects. They are somewhat effective,
but after a period of time their effect may diminish and the KS
Researchers have also experimented with new formulations of
chemotherapy drugs, which are designed to be less toxic. Two
such drugs, liposomal doxorubicin and liposomal daunorubicin,
are now approved for treating KS in the USA.
Liposomes are a method of enclosing a drug in microscopic
bubbles of fat. These have several theoretical advantages.
First, the liposomes circulate in the bloodstream without
releasing the drug. The drug is only released when the liposome
leaves the bloodstream and lodges in the body tissues. This is
most likely to happen within KS lesions, because the lesions
are made up of a mass of abnormally growing blood vessels that
are very 'leaky'. Thus, the chemotherapy is targeted to the
lesions, wherever they are in the body, with less of the drug
affecting non-cancerous areas and thus fewer side-effects.
Liposomal doxorubicin, also known by the tradename DOX-SL or
DOXIL, is made by Sequus Pharmaceuticals (formerly known as
Liposome Technology Inc.). Studies of liposomal doxorubicin
found that the best dose is between 10 and 20 mg/m2 given every
three weeks. Over 90% of treated people tend to have some
reduction in the number or size of their KS lesions. This is
difficult to compare with other trials as different methods are
often used to measure the tumour burden (number, size and
location of tumours).
The major side-effects are neutropenia, inflammation of the
mouth (stomatitis) and hair loss. These are side-effects seen
with the parent drug doxorubicin; however, doxorubicin's most
serious side-effect of damage to the heart muscle is far less
likely with the liposomal form. Some recipients have developed
an unusual side-effect of ulcers on the hands and feet, known
as hand-foot syndrome. Neutropenia caused by liposomal
doxorubicin or other drugs can be treated with an agent such as
G-CSF which promotes the growth of white cells.
At present liposomal doxorubicin is not approved in the UK, but
doctors can obtain it on a named patient basis. Not all HIV
centres currently offer treatment with liposomal doxorubicin
but many may treat individuals with the drug if requested.
Another chemotherapy drug, daunorubicin, is used in liposomal
form for treating KS, with similar response rates to liposomal
doxorubicin. It is approved in the USA where it is manufactured
by Vestar under the tradename DaunoXome, and available in the
UK on a named patient basis.
In a study at the Kobler Centre which enrolled people with
early KS, one group was treated immediately with liposomal
daunorubicin and the other group received no treatment. The
treated people had some improvement in their KS.
The results of trials comparing these liposomal drugs with
conventional chemo-therapy treatments for KS are due to be
presented at conferences in late September.
There has been no comparative trial of these two products so it
is unclear which will prove to be the best. They have been
anecdotal reports that people who have stopped responding to
one liposomal drug may benefit from switching to the other.
Several experimental treatments for KS are also currently being
studied in the UK. In 1994 the results of experiments using
mice with artificially induced KS lesions were reported. When
female mice became pregnant, the KS lesions became smaller or
disappeared altogether. Researchers found that a female hormone
produced at high levels during pregnancy seemed to be killing
the KS cells. A human form of this hormone, called human
chorionic gonadotrophin (HCG) is already a licensed treatment
for certain infertility problems.
Experiments using HCG as a treatment for people with KS have
produced mixed results. One group of researchers said that
injections of HCG caused lesions to shrink with few
side-effects; other groups, including doctors in London, found
that the injections had no obvious benefits but caused
substantial side-effects, including irritability and anxiety
serious enough to require psychiatric treatment. It is also
A trial at St Mary's Hospital is testing an ointment called
calcipotriol as a treatment for KS on the skin. For more
information see the report in AIDS Treatment Update issue 28.
Over the last year evidence has been accumulating which
suggests that KS may be caused by a virus that belongs to the
herpes family. The virus, called KSHV or HHV-8, has
consistently been found in cells taken from KS lesions. If KS
is caused by this virus, drugs that inhibit that virus could
help to treat KS.
One such treatment may be the anti-CMV drug foscarnet. In a
small study, Swedish researchers found that people with early
KS had reductions in the number and size of their KS lesions
when treated with foscarnet, although the drug seemed to have
no effects in people with advanced KS. A retrospective American
study published earlier this year suggested that people who
received anti-CMV treatment with foscarnet were also 70% less
likely to develop KS compared to people who did not receive
foscarnet, but a similar French study found no evidence of an
anti-KS effect of foscarnet. A trial comparing foscarnet versus
no treatment for KS is due to start later this year at three
London clinics. In the meantime, however, doctors do not view
foscarnet as a practical treatment for KS as it has to be
administered intravenously and has serious side-effects.