A combination of drugs that target new and existing blood vessels shows promise in a mouse model of cancer, according to a presentation at the joint annual meeting of the National Cancer Institute, the American Association for Cancer Research, and the European Organization for Research and Treatment of Cancer.

In the current work, Dietmar Siemann, Ph.D., and his American colleagues combined an experimental anti-angiogenesis agent with a drug that targets existing blood vessels as treatment for mice with transplanted kidney tumors or Kaposi’s sarcoma; they found that the combination was more effective in delaying tumor progression than either drug alone.

Treatment was begun when the transplanted human tumors were large enough to be detected on physical examination (tumor size roughly that of a pea). A total of 35 mice were involved in the protocol, in which the anti-angiogenesis agent ZD6474 was injected daily into the tumor mass for 7 days and the vascular targeting agent ZD6126 was injected on the Monday, Wednesday, and Friday of the same week. There were no apparent adverse effects from treatment.

"When we used only the anti-angiogenic drug in treating mice with kidney tumors and Kaposi's sarcoma, we achieved tumor growth delays of 25 and 15 days, and with the sole use of the vascular targeting drug we achieved tumor growth delays of 23 and 25 days," Siemann said. "But when we combined the 2 drugs in the treatment of mice with the same types of malignancies, we documented tumor growth delays of 55 and 86 days."

"Our findings seem more exciting in light of the fact we achieved these antitumor effects with the use of very nontoxic doses of the two selected drugs, and we were dealing with 2 forms of human cancer that are stubbornly difficult to treat," said Siemann. "In our latest study, we found that while some tumor types responded better than others, the antitumor response was always enhanced when the 2 treatments were combined. In one study, we were delighted to find that 3 of 8 treated mice were free of any indications of cancer a year after treatment, indicating they are cured."

The drug combination is now being studied in phase II clinical trials. Siemann suggested that additional research should explore drug benefits when used in conjunction with conventional chemotherapy, radiation, or both modalities.