Brouhaha Over Human Chorionic Gonadotropin (hCG) Yields, Again, To Sober Realism
Vesnarinone In the Wings
Per usual, AIDS related malignancies were the ugly step-sister of the X International Conference on AIDS, with only one formal session and a handful of posters dedicated to KS and AIDS-associated non-Hodgkin’s lymphoma. There were, however, some interesting data presented, and the myriad of posters were quite informative – one simply had to hunt them out.
Robert Gallo finally broke the news about human chorionic gonadotropin (hCG). In his speech, Gallo explained that female SCID mice with KS-like lesions from being injected with human KS cells suddenly had their lesions disappear when they became pregnant. His lab discovered that “KS malignant cells are under the control of a female pregnancy hormone called hCG.” When they injected hCG into tumor-bearing mice, Gallo noted that the beta sub-unit of hCG “prevents tumor formation and destroys pre-existing KS tumors in the mouse model.”
What was not mentioned was the fact that a hCG – an FDA approved drug manufactured by three companies for women to induce fertility and for men with inadequate testicle function – was tested almost a year ago on three male KS patients by a Kansas physician, Dr. Sharon Lee, who said she saw no anti-tumor activity. Lee believes that there is “too much alpha” and “not enough beta” in the already available brands of hCG, and that using pure beta hCG might be what is needed to induce responses.
USC’s Parkash Gill, one of the leading KS researchers and clinicians, just opened a small hCG trial – administered intralesionally – and has already treated at least one patient. Dr. Phillipe Herman will be conducting the same study at his facility in Belgium. Gill is still waiting for one of the companies to develop a pure beta hCG (possibly Serano Labs), but until then, he will be using currently available hCG, which is said to be 80% beta, 20% alpha.
Data was also presented by UCLA’s Dr. Steve Miles from the AIDS Clinical Trials Group (ACTG)’s interleukin-4 study. There has only been one partial response, but patients are showing a marked decrease in their p24 antigen levels. Investigators are still awaiting PCR results to ascertain if IL-4 affects viral load and also down-regulates IL-6 levels.
In vitro data of Vesnarinone (OPC8212) made by Otsuka Pharmaceuticals was presented in a poster session. Vesnarinone – an anti-hypertensive drug available in Japan which also inhibits TNF and IL-6 – is currently being studied in a phase II trial at UCLA as an anti-HIV agent because of its anti-TNF effect. One study showed how Vesnarinone was able to inhibit proliferation of AIDS-KS cells in culture. Vesnarinone is soon to be tested in a small study on patients with KS at UCLA. If it demonstrates significant anti-tumor effect, it will next be studied in a larger phase II trial through the ACTG. There was also interesting epidemiological data presented from two large Spanish and Italian studies. Most of the data presented was in accordance with what has been found to be status quo in the United States: (1) KS is under-reported, so we don’t have a clear picture – and probably won’t ever have – on the actual number of AIDS patients with KS; (2) KS is now largely a secondary AIDS diagnosis, it is presently not the first opportunistic infection which manifests in people with HIV; and (3) the mean CD4+ count of these KS patients is now much lower (often under 100 CD4s) than it was eight to ten years ago. The major difference in these studies compared to data we have in the US is the statistically significant percentage of cases of AIDS patients with KS that are classified as IVDUs, not as homosexuals. Many speculated that these IVDUs with KS had actually had homosexual contact but that homophobia of the Italian and Spanish societies prevented them from admitting to homosexual activity.
No experimental therapies were discussed for AIDS-associated non-Hodgkin’s lymphoma. One French study of the LNHIV-91 + G-CSF regimen (a large combination of six standard chemotherapy drugs plus granulocyte colony stimulating factor to prevent neutropenia) was administered to 31 chemotherapy-naive patients with peripheral and CNS lymphoma and a CD4+ T cell count over 100. Twenty-three (70%) of the patient achieved a complete response and had a median survival of 13 1/2 months.