Battling cutaneous disease

San Francisco

- Antiangiogenic agents show early promise in treating port wine stains and a host of cutaneous diseases, an expert says.

Pulsed dye lasers (PDLs) represent the standard of care for treating port wine stains, says Kristen M. Kelly, M.D., associate professor of dermatology and surgery, University of California, Irvine.

However, she says that when using PDLs for this purpose, "We have occasionally been frustrated because, while we often are able to help patients, some don't respond. Or they respond, then their lesion recurs."

Accordingly, she says she and her colleagues are interested in using antiangiogenic agents to remove unwanted cutaneous vascular lesions, such as hemangiomas, vascular malignancies and angiofibromas, as well as to prevent recurrence of port wine stains, vascular malignancies and telangiectasias.

Currently available antiangiogenic agents include monoclonal antibodies, such as Avastin and Lucentis (bevacizumab and ranibizumab, respectively, both made by Genentech), Macugen (pegaptanib, Pfizer) and Erbitux (cetuximab, Bristol-Myers Squibb), all of which target angiogenesis growth factors and/or their receptors, Dr. Kelly says.

As for skin diseases that researchers are targeting with antiangiogenic agents, Dr. Kelly says that melanoma garners perhaps the most attention. For example, she says ABT-510 (thrombospondin-1 analog, Abbott) is currently in phase 2 testing for metastatic melanoma.

Additionally, Dr. Kelly says researchers are prospectively testing bevacizumab in patients with metastatic melanoma who have failed multiple other therapies.

In Kaposi’s sarcoma, she says sirolimus has proven effective in treating Kaposi’s sarcoma in renal transplant patients while maintaining sufficient immunosuppression to prevent rejection (Campistol JM et al.J Am Soc Nephrol. 2006 Feb;17(2):581-589).

Similarly, Dr. Kelly says, "Hemangiomas are definitely an area that could be very responsive. For example, Aldara (imiquimod, Graceway) can have antiangiogenic effects, as well as other mechanisms of action, and has been used to treat hemangiomas (Welsh O et al.J Am Acad Dermatol. 2004 Oct;51(4):639-642).

Additionally, she says researchers have begun using propranolol for hemangiomas. In one study involving 11 children, all patients showed a change from intense red to purple, with lesion softening, within 24 hours of beginning propranolol therapy (Leaute-Labreze C et al.N Engl J Med. 2008 Jun 12;358(24):2649-2651).

Regarding port wine stains, Dr. Kelly says, "We’ve done some research in an animal model looking at bevacizumab in combination with laser therapy. We’re also halfway through a randomized clinical trial comparing PDL plus imiquimod to PDL plus placebo and have seen improved response with the PDL plus imiquimod (Kelly KM et al.J Biomed Optics (submitted 2008)."

"Psoriasis is not considered to be a disease related to angiogenesis," Dr. Kelly says. Rather, she says the more prominent theories regarding its causality focus on immune system activation and epidermal proliferation.

"But angiogenesis appears to occur in this disease, so it’s possible that anti-angiogenic agents might be helpful in battling psoriasis," she says.

Somewhat similarly, she says recent research into rosacea’s causes focuses on the role of cathelicidins, antimicrobial peptides which might be abnormally processed, resulting in inflammation and angiogenesis (Schauber J, Gallo RL.J Allergy Clin Immunol. 2008 Aug;122(2): 261-266). DT