interferon alfa-2a (PegIFN) may be an effective therapy for Kaposi's sarcoma (KS)
that has not responded to antiretroviral treatment or chemotherapy, Dutch
investigators report in the online edition of Clinical Infectious Diseases. Doctors in Rotterdam used PegIFN to
treat ten HIV-positive people with KS that had not resolved with standard
therapy. A complete or partial treatment response was observed in eight
durable until the end of follow up with a median PFS [progression free
survival] of 2 years,” comment the authors. “Our study provides a strong
rationale for further investigation of PegIFN in AIDS-KS.”
KS is the most
common AIDS-defining cancer. First-line treatment is standard combination
antiretroviral therapy and this achieves a complete response in most people.
However, cases of
KS progression have been observed in the context of HIV treatment and a
suppressed viral load. Moreover, many patients present with already extensive
or progressing disease that requires additional chemotherapy on top of HIV
can achieve good responses but carries a risk of immune reconstitution
inflammatory syndrome (IRIS), drug interactions and unpleasant side-effects.
“Treatment remains challenging, due to relapses, disease progression and
treatment toxicity,” note the authors.
Interferon alfa is
approved for the treatment of AIDS-related KS. The pegylated form of the drug
(PegIFN) has superior efficacy and is less toxic. Doctors in Rotterdam
therefore wanted to see if PegIFN in combination with antiretroviral therapy
was an effective treatment for advanced KS that had not resolved with standard
population consisted of ten people who were diagnosed with KS between 1991
and 2012. PegIFN therapy consisted of weekly subcutaneous injections with a 180
dose. The duration of therapy was not predefined. Instead it was based on the
speed and completeness of response.
Eight of the participants were gay men and two were African
women. KS was the first AIDS-defining illness in six people.
Therapy with PegIFN was provided between 2005 and 2012.
All the participants were taking HIV therapy when this treatment was started. Eight
people had an undetectable viral load at baseline and the two other
individuals achieved viral suppression after changing their antiretroviral combination.
All the patients had stage T1 KS, indicating a poor
prognosis. Seven participants had extensive cutaneous and visceral KS; two
individuals had extensive cutaneous disease and ulcerative KS of the lower
extremities; and the remaining patient had oral and visceral KS with lymph node
A treatment response was observed in eight participants. This
included seven individuals who cleared KS and one individual who had a partial
response. All these individuals maintained their response to the time of last
follow-up, a median of 645 days.
Treatment with PegIFN initially achieved a partial
response in another participant. However, disease progression including pulmonary
KS led to the discontinuation of PegIFN treatment. Cutaneous lesions responded
to a second course of therapy but the pulmonary lesions continued to progress.
The tenth patient was critically ill and died with 29 days
due to progressive KS and multicentric Castleman’s disease (a KS-like
All the participants experienced side-effects. However, none
were serious, nor led to the discontinuation of PegIFN therapy.
“In this observational study, the administration of PegIFN
for AIDS-KS resulted in a partial or complete remission of 8 of 10 patients,”
comment the investigators. They acknowledge that their findings are limited by
the design of the study, especially its lack of randomisation or a control arm.
Nevertheless, they believe their results show PegIFN could be an effective
therapy for KS and also provide a context for more research. “Future studies
could identify subgroups of patients that would benefit most from PegIFN and
provide information on optimal timing and duration of PegIFN,” suggest the
They conclude: “Combining PegIFN with HAART could be an
effective therapy in extensive or treatment refractory AIDS-KS.”