A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in patients with androgen-independent prostate cancer.

Purpose: Thalidomide is a potent teratogen that causes dysmelia in humans. Recently, in vitro data suggested that it inhibits angiogenesis. Prostate cancer is dependent on the recruitment of new blood vessels to grow and metastasize.

Angiostatin and endostatin: endogenous inhibitors of tumor growth.

Considerable progress has been made in the understanding of the molecular structure and mechanistic aspects of Angiostatin and Endostatin, endogenous angiogenesis inhibitors that have been shown to regress tumors in murine models. The growing body of literature surrounding these molecules and on the efficacy of these proteins is in part due to the ability to generate these proteins in recombinant systems as well characterized molecules. Recombinant human Angiostatin and Endostatin are in Phase I trials, following the manufacture of clinical grade material at large scale.

2-Methoxyestradiol: an endogenous antiangiogenic and antiproliferative drug candidate.

2-Methoxyestradiol, once considered an inacitve end-metabolite of estradiol, has recently emerged as a very promising agent for cancer treatment. It is orally active in a wide range of tumor models, and inhibits tumor growth at doses showing no clinical signs of toxicity. 2ME2 targets both the tumor cell and endothelial cell compartments by inducing apoptosis in rapidly proliferating cells and inhibiting blood vessel formation at several stages in the angiogenic cascade.

Liposomal vaccines.

Liposomes have been used therapeutically to deliver drugs to certain anatomical sites. The use of liposomes to deliver antigens, although not a new concept, has received less attention. At least two vaccines of nearly identical liposome base composition to our vaccines have been tested in humans.

Recombinant soluble CD4 therapy in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A phase I-II escalating dosage trial.

Study Objective: To study the safety and pharmacokinetics and to derive preliminary evidence on surrogate indicators of efficacy of recombinant soluble CD4 (rsCD4) in patients with the acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex.

Design: Open label, escalating dosage, phase I-II tolerance trial.

Setting: Massachusetts General Hospital, Cedars-Sinai Medical Center, and Stanford University Medical School, three tertiary care institutions and members of the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group.