News: METVAN effektiv gegen Hirnmetastasen?

Thursday July 19, 2001

SOURCE: Parker Hughes Cancer Center

METVAN Effective in Neutralizing the Growth and Spread of Breast and Brain Cancer Tumors

ROSEVILLE, Minn., July 19 /PRNewswire/ -- In a study described in the July issue of Clinical Cancer Research, researchers at the Parker Hughes Cancer Center found that the compound bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(IV){METVAN [VO(SO(4))(Me(2)-Phen)(20]} is effective in neutralizing the growth and spread of breast and brain cancer tumors.

During the study researchers injected human breast and glioblastoma, a form of brain cancer, cells into immuno-deficient mice. METVAN was shown to effectively kill human breast cancer cells in mice. Tumors in the METVAN treated mice developed much slower and were much smaller than in control mice that were not treated with METVAN. Another significant finding of the study was that treatment with METVAN was associated with a nearly complete inhibition of the process cancer cells undergo in order to metastasize, or spread. Inhibiting the spread of cancer is an important goal for researchers because survival rates and quality of life for cancer patients decline markedly once their cancer has begun to spread to other parts of the body.

"There is still more work that needs to be done in order to develop this drug but our results are encouraging. Not only does this study show that METVAN kills breast and glioblastoma cells, but it also shows that it is a potent inhibitor of cancer metastasis. By finding a way to stop the spread of cancer beyond the initial tumor we may be able to save many lives and improve the quality of life of our patients and this study demonstrates that METVAN may be one way of doing this," said Dr. Fatih Uckun, M.D., Ph.D., President and Director of the Parker Hughes Cancer Center and a co-author of the study.

There will be an estimated 193,700 new cases of breast cancer diagnosed this year in the United States. This year an estimated 40,600 American women will die of breast cancer. Brain cancer is known for its aggressive nature and poor prognosis compared with other cancers. Brain tumors are the second leading cause of cancer-related death among children younger than 15 years of age. The median survival time for patients with glioblastoma is less than one year.

Reference: Narla RK, Chen CL, Dong Y, Uckun FM. In Vivo Antitumor Activity of Bis(4,7-dimethyl-1,10-phenanthroline) Sulfatooxovanadium (IV) {METVAN. Clinical Cancer Research, 7(7):2124-2133, 2001 July.

SOURCE: Parker Hughes Cancer Center

Clin Cancer Res 2001 Jul;7(7):2124-33

In vivo antitumor activity of bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(IV) (METVAN [VO(SO4)(Me2-Phen)2]).

Narla RK, Chen CL, Dong Y, Uckun FM.

Parker Hughes Cancer Center, Department of Oncology, Parker Hughes Institute, St. Paul, Minnesota 55113, USA.

The compound bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(IV) (METVAN [VO(SO4)(Me2-Phen)2]), exhibits potent cytotoxicity against human cancer cells at low micromolar concentrations. At concentrations > or = 1 microM, METVAN treatment was associated with a nearly complete loss of the adhesive, migratory, and invasive properties of the treated tumor cell populations. METVAN did not cause acute or subacute toxicity in mice at dose levels ranging from 12.5 mg/kg to 100 mg/kg. Therapeutic plasma concentrations > or = 5 microM were rapidly achieved and maintained in mice for at least 24 h after i.p. bolus injection of a single 10 mg/kg nontoxic dose of METVAN. At this dose level, the maximum plasma METVAN concentration was 37.0 microM, which was achieved with a t(max) of 21.4 min. Plasma samples (diluted 1:16) from METVAN-treated mice killed 85% of human breast cancer cells in vitro. METVAN was slowly eliminated with an apparent plasma t(1/2) of 17.5 h and systemic clearance of 42.1 ml/h/kg. In accordance with its potent in vitro activity and favorable in vivo pharmacokinetics, METVAN exhibited significant antitumor activity and delayed tumor progression in CB.17 severe combined immunodeficient (SCID) mouse xenograft models of human glioblastoma and breast cancer. In these experiments, METVAN was administered in daily injections of a single nontoxic 10 mg/kg i.p. dose on 5 consecutive days per week for 4 consecutive weeks beginning the day after the s.c. inoculation of U87 glioblastoma or MDA-MB-231 breast cancer cells. At 40 days after the inoculation of tumor cells, the U87 tumor xenografts in the vehicle-treated control SCID mice were much larger than those of the mice treated with METVAN (4560 +/- 654 mm(3) versus 1688 +/- 571 mm(3); P = 0.003). Similarly, the MDA-MB-231 tumors in SCID mice treated with METVAN were much smaller 40 days after tumor cell inoculation than those of the vehicle-treated control SCID mice (174 +/- 29 mm(3) versus 487 +/- 82 mm(3); P = 0.002). The favorable in vivo pharmacodynamic features and antitumor activity of METVAN warrants further development of this novel oxovanadium compound as a potential new anticancer agent.