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Lani · 01-07-2007, 07:45 PM

GROWTH FACTOR PATHWAY BLOCKING AGENTS
New anticancer therapies including small molecules and antibodies that block growth factor pathways are now in clinical trials and have shown considerable promise in combination with standard therapies in limiting the growth of some cancers. Examples of such drugs are herceptin, a blocking antibody to the Her-2/neu growth factor receptor, Iressa (ZD1839), a small molecule that prevents phosphorylation and activation of the epidermal growth factor receptor, and C225, a blocking antibody against epidermal growth factor receptor. In mouse xenograft models, C225 significantly inhibited tumor growth in combination with doxorubicin, but had only a modest effect alone. 42 C225 is now in clinical trials. Herceptin has already shown promise in a phase III trial in combination with first-line chemotherapy, 43 and has gained Food and Drug Administration approval in combination with other chemotherapeutic agents for the treatment of advanced breast cancer. Interestingly, the manufacturer has assigned a pregnancy risk category of B to herceptin based on extensive trials in monkeys without apparent fetal harm. Placental transfer in monkeys was demonstrated. No information is yet available about the effects of herceptin in human pregnancy; however, as the Her-2/neu pathway is critical to fetal development, the possibility of fetal damage in humans has not been excluded. At this time, the author recommends that management of cancer in pregnancy should limit the use of growth factor pathway blockers until more information is available. However, the possibility also exists, as suggested by the animal data, that such agents may result in a more favorable outcome in pregnancy for mother and fetus compared with standard chemotherapy. Additional information on the effects of such agents in pregnancy is clearly needed.

01-07-2007, 07:45 PM	#4
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	from 2002 GROWTH FACTOR PATHWAY BLOCKING AGENTS New anticancer therapies including small molecules and antibodies that block growth factor pathways are now in clinical trials and have shown considerable promise in combination with standard therapies in limiting the growth of some cancers. Examples of such drugs are herceptin, a blocking antibody to the Her-2/neu growth factor receptor, Iressa (ZD1839), a small molecule that prevents phosphorylation and activation of the epidermal growth factor receptor, and C225, a blocking antibody against epidermal growth factor receptor. In mouse xenograft models, C225 significantly inhibited tumor growth in combination with doxorubicin, but had only a modest effect alone. 42 C225 is now in clinical trials. Herceptin has already shown promise in a phase III trial in combination with first-line chemotherapy, 43 and has gained Food and Drug Administration approval in combination with other chemotherapeutic agents for the treatment of advanced breast cancer. Interestingly, the manufacturer has assigned a pregnancy risk category of B to herceptin based on extensive trials in monkeys without apparent fetal harm. Placental transfer in monkeys was demonstrated. No information is yet available about the effects of herceptin in human pregnancy; however, as the Her-2/neu pathway is critical to fetal development, the possibility of fetal damage in humans has not been excluded. At this time, the author recommends that management of cancer in pregnancy should limit the use of growth factor pathway blockers until more information is available. However, the possibility also exists, as suggested by the animal data, that such agents may result in a more favorable outcome in pregnancy for mother and fetus compared with standard chemotherapy. Additional information on the effects of such agents in pregnancy is clearly needed.