GMHC Treatment Issues 1994 Oct 1; 8(9): 5
One of the most exciting reports on Kaposi's sarcoma came from
Robert Gallo's laboratory at the U.S. National Cancer
Institute. As reported in Treatment Issues' August edition,
Gallo's group observed that nude pregnant mice who had been
injected with a KS cell line did not develop tumors during the
first trimester of pregnancy whereas KS lesions flourished
during the second and third trimester. The researchers
concluded that the beta subunit of the hormone human chorionic
gonadotropin (HCG), which is high early in pregnancy, was
responsible for the anti-tumor effect seen in the mice.
Data on the use of chemotherapeutic agents encapsulated within
liposomes (tiny fat globules that regulate the passage of the
entrapped drug from the blood stream to specific sites - see
April 1994 Treatment Issues), were presented by various groups
of investigators who have successfully used these agents in
patients with AIDS-related KS.
- DOX-SL: The best results to date were seen in the
International DOX-SL Study, a multicenter European and
Australian phase II/III study of 247 KS patients. DOX-SL is a
preparation of doxorubicin encapsulated in "stealth"
liposomes that deliver significantly greater quantities of
the drug to the KS lesions. "Stealth" liposomes incorporate a
protective polyethylene glycol (PEG) coating allowing them to
circulate in the bloodstream for up to 48 hours or more.
Conventional uncoated liposomes are cleared from the blood in
a few hours. (By comparison, unencapsulated - "free" - drug
disappears from blood in a matter of minutes.)
The patients were treated with DOX-SL intravenously using a 30
minute infusion every two weeks. Patients were started at 10 or
20 mg/m2 of body area, and the dose was titrated upward if KS
lesions failed to respond. Two-thirds of the trial participants
received at least six infusions. Of the 133 for whom response
data are available, three (1.8 percent) attained a complete
response, 81 (48.5 percent) a partial response and 38 (22.8
percent) had stable disease. Partial or complete responses were
typically seen within two or three cycles of DOX-SL. Side
effects included nausea (25 percent), vomiting (13.9 percent),
stomatitis (11.8 percent), diarrhea (24.9 percent) and hair
loss (11.8 percent). Significant neutropenia occurred in 17.9
percent of all treatmentcycles whereas anemia and
thrombocytopenia occurred in 21.6 percent and 12 percent of all
On September 7, 1994, Liposome Technology, Inc., the
manufacturers of DOX-SL, filed a New Drug Application (NDA)
with the U.S. Food and Drug Administration for the treatment of
KS in people with AIDS who cannot tolerate or have failed
conventional chemotherapy. (Until this application is approved,
people with KS and intolerant to ABV, a standard anti-cancer
therapy, can receive DOX-SL through a special open-label trial
accessible through 30 sites nationwide. Call Liposome
Technology at 415/323-9011 for more information.)
- Daunoxome: Daunoxome is the drug daunorubicin encapsulated by
a conventional liposome. The first phase II study of
daunoxome was presented in Yokohama. Through February
1994, 42 patients had been treated with Daunoxome every two
weeks. One-third of the patients had a partial response and
the other two-thirds had stable disease. The median duration
of the response with the 40 mg dose was 7.5 to nine weeks,
depending on the dose. The main side effect was neutropenia,
which could be managed with G-CSF (Neupogen).
The Yokohama Conference heard the first clinical data on the
use of interleukin-4 (IL-4) in patients with KS. IL-4
promotes CD4 cell proliferation and also suppresses
interleukin-6 production - as well as KS cells in culture. IL-6
is found in high levels in patients with KS and is implicated
in the pathogenesis of KS lesions.
The phase I/II study (ACTG 224) enrolled patients with
biopsy-proven KS who had IL-4 administered subcutaneously in
escalating doses. So far, thirteen trial participants have
received one of two dose levels. Side effects such as fever,
fatigue and headaches were very common. Only three patients
experienced a partial response. The dose limiting toxicity to
date has been neutropenia. On the other hand, significant
decreases (60 percent) in HIV p24 antigen levels were observed
in all patients, which raises the possibility that IL-4 is
useful as an anti-HIV drug.
1 Goebel FD et al. Tenth international conference on
AIDS abstract book. Aug 7-12 1994; I(abstract PB0123):174.
2 Wernz JC et al. Tenth international conference.
3 Miles SA et al. Tenth international conference.
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