Kaposi's Sarcoma: Taxol, TNP-470 Trials at National Cancer Institute

Two separate trials of novel KS treatments are now recruiting
at the U.S. National Cancer Institute, in Bethesda, Maryland.
One is testing Taxol, which is best known as a treatment for
ovarian cancer. Another is testing TNP-470, one of a new class
of drugs which works by inhibiting blood vessel growth, when
such growth is not wanted. (KS is caused by abnormal growth of
blood vessel.) For background on TNP-470 (previously called
AGM-1470), see AIDS TREATMENT NEWS #135, September 20, 1991.

On November 15, AIDS TREATMENT NEWS received an electronic mail
message from the researchers about the current studies:

"Please see below for description of the trials. Of note, we
have had a number of good responses to Taxol with fairly mild
toxicity (slight fatigue, brief myelosuppression, and hair
loss). Also, our trial of the novel angiogenesis inhibitor TNP-
470 has caused *no* clear toxicity to date, and the one patient
on the highest dose level may be responding to this drug.

"We are intrigued by these early results and would like to
enroll these studies as rapidly as possible. However, patients
have been scarce, especially for the TNP-470 trial (which is
quite time-consuming, with its every-other-day administration
schedule)."

All treatment costs are paid by the National Cancer Institute.
On the first visit, for screening, volunteers must cover their
own travel expenses; later, they will be paid for travel home,
or $45 per day when they stay in the Bethesda area. Volunteers
often rent rooms from families near the National Institutes of
Health campus, which is less expensive than staying in a hotel.

Taxol

"Paclitaxel (Taxol) is a drug derived from the Pacific yew tree
that has been found to be effective against ovarian carcinoma.
We are presently testing the activity of paclitaxel in a Phase
II study in patients with Kaposi's sarcoma. Paclitaxel will be
administered as a three hour infusion every 21 days in an
outpatient setting. Activity and response will be determined.
In addition, the toxicity profile in HIV-positive patients will
be identified. Patients must be on a stable regimen of single
dose or combination antiretroviral therapy for one month before
entry. Patients also must have received no more than one prior
regimen of cytotoxic chemotherapy (for the purpose of this
protocol, vincristine and vinblastine are considered as a
single regimen) and are required to be off chemotherapy,
radiation, intralesional therapy and interferon for one month
before starting taxol. Patients with pulmonary KS causing
substantial symptoms (e.g. dyspnea with minimal exercise) or
with other acute, life-threatening KS will be ineligible for
this study. For more information, please contact Jill Lietzau
at 301-496-8959, or Wayne Saville, M.D., at 301-402-3630."

TNP-470

"TNP-470 is a an analog of the fungal product fumagillin that
has been shown to be a potent inhibitor of angiogenesis. It is
different from most traditional anti-cancer drugs in that it
has caused little or no bone-marrow toxicity or
immunosuppression in test animals. The major toxicity in
animals (seen when it was given as a bolus) has been bleeding.
We are recruiting patients for a Phase I trial with this agent
in patients with Kaposi's sarcoma. Patients will receive TNP-
470 every other day for 6 weeks. If the drug is well tolerated,
patients will have the option to receive it for up to an
additional 12 weeks. Because the drug is given by vein every
other day, patients must be from the DC area or must stay in
the Maryland/D.C. area for the entire treatment. The toxicity,
pharmacokinetics and activity of TNP-470 will be studied.
Different patients will receive increasing doses of TNP-470
until the maximum tolerated dose is identified. Patients must
be on a stable dose of single-agent or combination
antiretroviral therapy for one month before starting TNP, and
are required to be off chemotherapy, radiation, intralesional
therapy and interferon for three weeks before starting the
trial. For more information, please contact Kathy Wyvill or
Jill Lietzau at 301-496-8959 or James Pluda, M.D., at (301)
496-1196."