>>Trisenox and solid tumors have not yet found each other.<<
Huh?
clinicaltrials.gov
clinicaltrials.gov
clinicaltrials.gov
clinicaltrials.gov
clinicaltrials.gov
>>The Oncologist, Vol. 6, Suppl 2, 22-28, April 2001
Clinical Trials of Arsenic Trioxide in Hematologic and Solid Tumors: Overview of the National Cancer Institute Cooperative Research and Development Studies
Anthony J. Murgo
Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
Correspondence: Anthony J. Murgo, M.D., Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, 6130 Executive Blvd., EPN Suite 7131, Rockville, Maryland, 20852-4910, USA. Telephone: 301-496-1196; Fax: 301-402-0428; e-mail: Murgoa@ctep.nci.nih.GOV
Arsenic trioxide inhibits growth and promotes apoptosis in many different cancer cell lines. The National Cancer Institute is working cooperatively with research centers across the U.S. to evaluate its clinical activity in hematologic malignancies, such as acute promyelocytic leukemia, acute myeloid leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, myelodysplastic syndrome, and multiple myeloma. It is also supporting research in solid tumors, such as advanced hormone-refractory prostate cancer and renal cell cancer and in cervical cancer and refractory transitional cell carcinoma of the bladder. The safety and pharmacokinetics of arsenic trioxide are also being evaluated in pediatric patients with refractory leukemia and lymphoma. The results of these ongoing studies should provide important insights into the clinical utility of arsenic trioxide in these diseases. <<
Cautionary note:
>>Toxicological Sciences 76, 271-279 (2003)
Arsenic Stimulates Angiogenesis and Tumorigenesis In Vivo
Nicole V. Soucy*, Michael A. Ihnat, Chandrashekhar D. Kamat, Linda Hess, Mark J. Post, Linda R. Klei*, Callie Clark and Aaron Barchowsky*,,1
* Departments of Pharmacology and Toxicology and Physiology, Dartmouth Medical School, Hanover, New Hampshire 03755; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190
Trivalent inorganic arsenic (arsenite, arsenic trioxide, As[III]) is currently being used to treat hematologic tumors and is being investigated for treating solid tumors. However, low concentrations of As(III) stimulate vascular cell proliferation in cell culture, although this has not been confirmed in vivo. Therefore, the hypothesis that As(III) enhances blood vessel growth (angiogenesis) and tumorigenesis was tested in two in vivo models of angiogenesis and a model of tumor growth. In the first, arsenite caused a dose-dependent increase in vessel density in a chicken chorioallantoic-membrane (CAM) assay. The threshold As(III) concentration for this response was 0.033 µM and inhibition of vessel growth was observed at concentrations greater than 1 µM. Mouse Matrigel implants were used to test the angiogenic effects of As(III) in an adult mammalian system. Mice were injected with 0.8–80 µg/kg As(III)/day over a three-week period. During the last two weeks, Matrigel plugs were placed on the abdominal wall. Low and high doses of As(III) were synergistic with fibroblast growth factor-2 (FGF-2) in increasing vessel density in the Matrigel assay, while a middle dose had no effect. To test the effects of As(III) on tumor growth, GFP-labeled B16-F10 mouse melanoma cells were implanted in nude mice, which subsequently received biweekly injections of 0.5–5.0 mg/kg As(III). Significant tumor growth and lung metastasis was seen in all animals, with the largest tumors occurring in animals treated with lower doses of As(III). These studies support the hypothesis and indicate that induction of angiogenesis, enhanced tumor growth, and metastasis are potential dose-dependent toxic side effects of arsenic therapies.<<
Aside to Nigel: TELK ahead? Yes, but the above solid tumor trials for Trisenox are in PII. Telcyta just began PIII in fewer indications. Telcyta is the better drug, being less toxic.
Cheers, Tuck |
