Comparison of several antiangiogenic regimens alone and with cytotoxic therapies in the Lewis lung carcinoma

Cancer Chemother Pharmacol. 1996;38(2):169-77. doi: 10.1007/s002800050466.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Lewis Lung / drug therapy*
  • Cell Survival / drug effects
  • Drug Synergism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Tumor Cells, Cultured


  • Antineoplastic Agents