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Lesion Liberation Unlikely: KS Proves Formidable Foe As Angiogenesis Inhibitors and Stealth Chemotherapy Fall Short of Expectations
Pregnant Mice the Key?

May 1994

Michael Marco recently returned from a transcontinental tour of KS research laboratories. While his official report is not due out for another week or so, he was kind enough to forward a rough copy of his travelogue for excerption here in TAGline.

Los Angeles. Interviews with Steve Miles and Ron Mitsuyasu at UCLA, both of whom have years of experience treating HIV+ people with KS. They are not afraid of trying new compounds in a phase I setting, Michael writes. In the past they have tried pentoxyfilline, CD8+ and also Roche's dreaded tat antagonist -- which appeared to make KS lesions worse.

At present, UCLA is the only site in the country trying the soluble TNF receptor (Immunex, rhuTNFr:Fc) for KS and are about to start on 9-cis retinoic acid for KS. Its sister compound, the much talked about all-trans retinoic acid (being tested at a few sites around the country) has met with questionable results. Nobody seems to be able to get the dosing down. At high doses, Jamie von Roenn (Northwestern) saw an exacerbation of KS lesions. Not good. Parkash Gill (USC), however, reports a number of complete and partial responses.

Steve Miles is also trying recombinant IL-4 for KS. IL-4 was touted as the thing because it has been shown to down-regulate IL-6 in vitro, And IL-6 is one of the major cytokines that stimulates endothelial cells. It was hoped that IL-4 would be the quick answer -- a home run. So far, only one partial response has been seen. Contrary to what everybody thought, and as Gene Shearer had warned, 'IL-4 is the worst thing you can give to somebody with HIV,' IL-4 did not up-regulate virus. In fact, Steve is seeing dramatic decreases in p24 antigen. He is quite vocal about how KS patients should and should not be treated. The man knows his shit and is one of the few researchers who will really say it.

San Francisco. Meetings with Larry Kaplan, Don Abrams, James Kahn and Robert Robles. They are all big at SFGH where some interesting work is being done. One of the guys (the aspiring 'Gang of Five-r' who can't chose between KS, nucleosides and vaccines) wasted my time.

Most enlightening and helpful was Don Abrams. He not only made referrals to three people who later gave great interviews, but he provided valuable insight into his analysis of treating KS patients for more than ten years now. When I mentioned that KS trials didn't seem to be enrolling well, Abrams shot back, 'Of course they aren't, people are burned out, disillusioned, and can't or won't get interested about every new thing that comes along. There has been too much disappointment in the past.' The man is right.

DOX-SL. The makers of DOX-SL (formerly DOXIL) screwed up last month by trying to close enrollment to the salvage protocol 30-12. This would have meant that DOXIL would not be available to patients who needed it and the only other chance of getting DOXIL was the hope that one would get randomized to it in the DOX-SL vs. ABV (30-10) trial.

Dr. Susan Krown (MSK, ACTG Oncology and Executive Committees, and a smart, out-spoken Jewish gal), with the help of TAG, got LTI {Liposome Technology Inc.) to change its mind and re-open 30-12 for enrollment.

With the help of Mark [Harrington], I sent out letters to the 33 principal investigators of 30-12 and told them that they should call all the people they had turned away and enroll patients ASAP. LTI's badly timed and planned decision to close the trial was based on not unreasonable financial considerations. (LTI has been around for 10 years with only $40 million left in the bank and has yet to bring a single drug to market.) LTI wants to close 30-12 for enrollment and set up a nationwide treatment IND. That way the company won't have to spend its money on data monitoring and infusion costs.

NCI. Broder, Gallo, Feigal, et al. The 4 1/2 hour meeting with Sam Broder was overwhelming and included 11 presentations.

Gallo was cool. He presented his version of angiogenesis and talked about the various cytokines involved. He also alluded to the supposedly confidential research surrounding a pregnancy hormone as treatment for KS. One of the questions they are trying to answer is 'Why can't we give pregnant mice KS?' Anyway, his work is quite interesting. He has a dedicated lab and is willing to share his knowledge. He would like more and easier access to tissue samples. This is being addressed by the NCI. It has put out an RFA for researchers to set up tissue banks. The ACTG should and will jump on this.

Angiogenesis. Patients are not accruing for the 3 phase I/II trials of Tecogalan (SPPG), TNP-470 (Taxol) and platelet factor 4 (rhPF-4). Nobody seems to know that these trials exist or what good might come out of being in one.




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