Solid tumors in general, and breast cancer in particular, depend on angiogenesis to grow and metastasize. Multiple agents have been developed in order to inhibit this phenomenon of tumor-induced angiogenesis. TNP-470 is one of the most potent of these drugs. We report here a case of regression of metastatic lesions from breast cancer due to the administration of the anti-angiogenic drug TNP-470.
Methods
A 44-year-old woman with a history of stage 2 breast cancer developed metastases at four sites: eye, lung, liver, and bone. She had been treated with radiation, megace, adriamycin, Cytoxan, and 5-fluorouracil with disease stabilization. After she completed her radiation and chemotherapy, she was started on TNP-470.
Results
In response to TNP-470, her disease showed a partial response at the three-month follow-up and stabilization at the five-month follow-up. There were no side effects, and her quality of life was good.
Conclusions
To our knowledge, this patient is the first reported case of regression of breast cancer metastases as a result of treatment with TNP-470. Anti-angiogenic drugs hold promise for the future therapy of breast cancer, and possibly of many other solid tumors as well.
BelmanN., BonnemE.M., HarveyH.A., LiptonA.: Phase I trial of recombinant platelet factor 4 (rPF4) in patients with advanced colorectal carcinoma. Invest. New Drugs, 14: 387–389, 1996.
2.
DeVitaV.T.Jr., HellmanS., RosenbergS.A.: Cancer: principles and practice of oncology.Philadelphia, Lippincott-Raven, 1997.
3.
DeVoreR.F., HellerqvistC.G., WakefieldG.B., WamillB.D., ThurmanG.B., MintonP.A., SundellH.W., YanH.P., CarterC.E., WangY. F., ZhangM.H., JohnsonD.H.: Phase I study of the antineovascularization drug CM101. Clin. Cancer Res., 3: 365–372, 1997.
4.
DezubeB.J., Von RoennJ.H., Holden-WiltseJ., RemickS., ColleyT.P., CheungT.W., SommadossiF.P., MooreJ., ShriverS., SuckowC., GillP.: Fumagillin analog (TNP-470) in the treatment of Karposi's sarcoma: a phase I AIDS clinical trial group study. Natl. AIDS Malign. Conf., A35, 1996.
5.
EckhardtS.G., BurrissH.A., EckardtJ.R., WeissG., RinaldiD., BarringtonR., SmithL., FieldS., KuhnJ., SmithS., SmetzerL., MarcusS., MasuoK., SobelR., Von HoffD.D.: Initial phase I assessment of the novel angiogenesis inhibitor DS 4152 (Tecogalan sodium). Proc ASCO, 13: 55, 1994.
6.
EzekowitzR.A.B., MullikenJ.B., FolkmanJ.: Interferon al-fa-2a therapy for life-threatening hemangiomas of infancy. N. Engl. J. Med., 326: 1456–1463, 1992.
7.
FolkmanJ., Angiogenesis in cancer, vascular, rheumatoid and other disease. Nature Med., 1: 27–31, 1995.
8.
GradisharW.J.: An overview of clinical trials involving inhibitors of angiogenesis and their mechanism of action. Invest. New Drugs, 15: 49–59, 1997.
9.
HoriA., IkeyamaS., SudoK.: Suppression of cyclin D1 mRNA expression by the angiogenesis inhibitor TNP-470 (AGM-1470) in vascular endothelial cells. Biochem. Biophys. Res. Comm., 204: 1067–1073, 1994.
10.
IngberD., FujitaT., KishimotoS., SudoK., KanamaruT., BremH., FolkmanJ.: Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature, 348: 555–557, 1990.
11.
KohnE.C., ReedE., SarosyG., ChristiannM., LinkC.J., ColeK., FiggW.D., DavisPA., JacobJ., GoldspielB., LiottaL.A.: Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers. Cancer Res., 56: 569–573, 1996.
12.
KudelkaA.P., LevyT., VerschraegenC.F.: A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix. Clin. Cancer Res., 3: 1501–1505, 1997.
13.
LushR.M., FiggW.D., PludaJ.M., BittonR., HeadleeD., KohlerD., ReedE., SartorO., CooperM.R.: A phase I study of pentosan polysulfate sodium in patients with advanced malignancies. Ann. Oncol., 7: 936–944, 1996.
14.
MasakazuT., YamamotoY., ImazawaT., AkutsuK., TominagaT.: Antitumor effect of the angiogenesis inhibitor AGM-1470 and its combination effect with tamoxifen in DMBA induced mammary tumors in rats. Int. J. Oncol., 3: 525–528, 1993.
15.
NorthfeltD.W., RoblesR., LangW., WagnerB., KahnJ., BonnemE.: Phase I/II study of intravenous (IV) recombinant platelet factor 4 (rPF4) in AIDS-related Kaposi's Sarcoma (KS). Proc. ASCO, 14: 288, 1995.
16.
O'ReillyM.S., HolmgrenL., ShingY., ChenC., RosenthalR.A., MosesM., LaneW.S., CaoY., SageE.H., FolkmanJ.: Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell, 79: 315–328, 1994.
17.
O'ReillyM.S., BoehmT., ShingY., FukaiN., VasiosG., LaneW.S., FlynnE., BirkheadJ.R., OlsenB.R., FolkmanJ.: Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell, 88: 277–285, 1997.
18.
PludaJ.M., WyvillK.K., LietzauJ., FiggW.D., WhitcupS.M., FeigalE., HumphreyR., WellesL., YarchoanR.: A phase I trial administering the angiogenesis inhibitor TNP-470 (AGM-1470) to patients with HIV-associated Kaposi's Sarcoma (KS). Natl. AIDS Malign. Conf., A19, 1996.
19.
SinN., MengL., WangM.Q.W.: The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. Proc. Natl. Acad. Sci., 94: 6099–6103, 1997.
20.
SinghY., ShikataN., KiyozukaY., NambuH., MorimotoJ., KurebayashiJ., HiokiK., TsuburaA.: Inhibition of tumor growth and metastasis by angiogenesis inhibitor TNP-470 on breast cancer cell lines in vitro and in vivo. Breast Cancer Res. Treat., 45: 15–27, 1997.
21.
SutoA., KubotaT., MatsuzakiS.W., TakeshitaT., SatoS., HoffmanR.M., KitajimaM.: Effect of the antiangiogenesis agent AGM-1470 (TNP-470) on lung micrometastasis of rodent mammary tumors in nude mice. Breast Cancer Res. Treat., 32(Supp): 60, 1994.
22.
TeicherB.A., HoldenS.A., DupuisN.P., KakejiY., IkebeM., EmiY., GoffD.: Potentiation of cytotoxic therapies by TNP-470 and minocycline in mice bearing EMT-6 mammary carcinoma. Breast Cancer Res. Treat., 36: 227–236, 1995.
23.
TulpuleA., SnyderJ.C., EspinaB.M., HigashiL., SatomiM., LombardyE.E., GillP.S.: A phase I study of Tecogalan, a novel angiogenesis inhibitor in the treatment of AIDS-related Kaposi's Sarcoma and solid tumors. Retroviral Dis., A248, 1996.
24.
TNP-470: information for clinical investigators.Deerfield: TAP Holdings Inc., 1997.
25.
Wojtowicz-PragaS., LowJ., MarshallJ., NessE., DicksonR., BarterJ., SaleM., McCannP., MooreJ., ColeA., HawkinsM.J.: Phase I trial of a novel matrix metalloproteinase inhibitor batimastat (BB-94) in patients with advanced cancer. Invest. New Drugs, 14: 193–202, 1996.
26.
YamaokaM., YamamotoT., IkeyamaS., SudoK., FujitaT.: Angiogenesis inhibitor TNP-470 (AMG-1470) potently inhibits the tumor growth of hormone-independent human breast and prostate carcinoma cell lines. Cancer Res., 53: 5233–5236, 1993.
27.
YamamotoY., ToiM., YamadaR., TominagaT.: Combination effect of an angiogenesis inhibitor AGM-1470 with 5'-deoxy-5-fluorouridine and with hormonal drugs in DMBA-induced rat mammary tumors. Oncol. Rep., 2: 793–796, 1995.
