Comparison of several antiangiogenic regimens alone and with cytotoxic therapies in the Lewis lung carcinoma.
The efficacy of several potential antiangiogenic agents, TNP-470, minocycline, suramin, genistein, interferon delta 4, 14(sulfated)-beta-cyclodextrin and tetrahydrocortisol, alone and in combination with cytotoxic therapies was examined against primary and metastatic Lewis lung carcinoma. The antiangiogenic agents when administered as single agents or in two-agent combinations were only modestly active as antitumor agents. Three antiangiogenic agent combinations, TNP-470/minocycline, TNP-470/14(SO4)beta-CD/THC and minocycline/14(SO4)beta-CD/THC, produced significant increases in tumor growth delay and decreases in the number of lung metastases when administered along with cyclophosphamide compared with cyclophosphamide alone. Two antiangiogenic agent combinations, minocycline/interferon delta 4 and minocycline/14(SO4)beta-CD/THC, produced significant decreases in the number of lung metastases when administered alone with adriamycin compared with adriamycin alone. The antiangiogenic combinations of TNP-470/minocycline, TNP-470/suramin, TNP-470/genistein, TNP-470/interferon delta 4 and TNP-470/l4(SO4)beta-CD/THC, resulted in increased tumor growth delays when administered along with CDDP, BCNU, fractionated radiation or 5-fluorouracil. There was not always a direct correlation between the antiangiogenic regimen that was most beneficial against the primary tumor as compared with disease metastatic to the lungs. These studies establish that a broad range of antiangilogenic therapies can interact in a positive manner with cytotoxic therapies.
Teicher
B A
BA
Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Holden
S A
SA
Ara
G
G
Korbut
T
T
Menon
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents