Antiangiogenic agents potentiate cytotoxic cancer therapies against primary and metastatic disease

• Published in: Cancer research (Chicago, Ill.) Vol. 52; no. 23; pp. 6702 - 6704
• Main Authors: TEICHER, B. A, ALVAREZ SOTOMAYOR, E, ZHEN DONG HUANG
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-12-1992
• Subjects: Animals; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; beta-Cyclodextrins; Biological and medical sciences; Bleomycin - administration & dosage; Chemotherapy; Cisplatin - administration & dosage; Cyclodextrins - pharmacology; Doxorubicin - administration & dosage; Drug Screening Assays, Antitumor; Drug Synergism; Lung Neoplasms - drug therapy; Lung Neoplasms - radiotherapy; Lung Neoplasms - secondary; Medical sciences; Mice; Mice, Inbred C57BL; Minocycline - pharmacology; Neoplasm Transplantation; Pharmacology. Drug treatments; Tetrahydrocortisol - pharmacology; Tumor Cells, Cultured; Antineoplastic agent; Steroid; Corticosteroid; Lewis lung carcinoma; Drug combination; Tetracycline derivatives; Malignant tumor; Angiogenesis; Chemotherapy; Cyclodextrin; Experimental disease; Treatment; Advanced stage; Inhibition; Neovascularization
• ISSN: 0008-5472; 1538-7445

The formation of a blood supply (angiogenesis) is critical to the growth of solid tumors. The naturally occurring steroid tetrahydrocortisol, the synthetic cyclodextrin derivative beta-cyclodextrin tetradecasulfate, and the tetracycline derivative minocycline have antiangiogenic activity. Tetrahydrocortisol and beta-cyclodextrin tetradecasulfate in a 1:1 molar ratio by continuous infusion over 14 days and minocycline administered i.p. over 14 days from day 4 to day 18 postimplantation of the Lewis lung carcinoma significantly increased the growth delay of the primary tumor after treatment with cis-diamminedichloroplatinum(II), melphalan, cyclophosphamide, Adriamycin, bleomycin, and radiation therapy administered in standard regimens. Addition of the antiangiogenic agents to treatment with the cytotoxic therapies not only reduced the number of lung metastases formed from the primary tumor but also reduced the number of large metastases. Five of 12 animals treated with the antiangiogenic modulators and cyclophosphamide were long-term survivors (> 120 days). Thus, antiangiogenic therapies can potentiate the efficacy of standard anticancer therapies.