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Page 2
Slowly growing tumors
Poorly vascularized tumors There is a common misconception that anti-angiogenic therapy is only effective in highly vascularized tumors. However, it appears that the lower the vascularity of the tumor, the more effective is the angiogenesis inhibitor treatment at a given dosage level. Multiple tumors Occasionally a situation arises that after the surgical removal of a large tumor, the growth of secondary tumors rapidly ensues. This phenomenon may be at least partially due to the fact that the large tumor is secreting enzymes that activate angiogenesis inhibitors. With the removal of this stimulus, there is nothing to inhibit the growth of the secondary tumors. The co-administration of angiogenesis inhibitors at the time of surgical, radiological or chemotherapeutic treatment can help to prevent the occurrence of secondary tumors. Combining angiogenic inhibitor treatment with chemotherapy Chemotherapy commonly involves administering the drugs at high dosages in an attempt to kill all the cancer cells, followed by periods without treatment. Unfortunately, this procedure is often highly toxic, leads to the development of drug resistance among the surviving cancer cells, and to increased vascularization of the tumor between treatments. A newly emerging therapy involves a dose schedule that combines a lower dose of chemotherapeutic drugs with a dosage that maintains a constant concentration of angiogenesis inhibitor in the circulation. 2 This procedure promises to avoid many of the problems mentioned above, and to be a more effective treatment. The question often arises whether anti-angiogenics can compromise the effectiveness of chemotherapy. Since angiogenesis inhibitors reduce the vascularity of the tumor, it would seem that this would result in reduced delivery of chemotherapeutic drugs to the tumor cells. However, the reverse seems to be the case. The increased delivery may be due to decreased pressure within the tumor. Combining angiogenic inhibitors with radiotherapy Radiation oncologists were initially concerned that anti-angiogenic therapy would reduce the effectiveness of radiation. It was assumed that ant-angiogenic drugs exerted their effect through reduced delivery of oxygen to the tumor cells, and it is known that these hypoxic (oxygen deprived cells) are less sensitive to radiation. However, again the reverse seems to be the case. In the first few weeks of therapy, at least, anti-angiogenics actually increased blood flow and oxygen delivery to the tumor, resulting in increased sensitivity to radiotherapy.
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