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Originally used in oncology for chronic myeloid leukemia, targeted anticancer therapies have found their niche in dermatology, effectively treating diseases, such as hypereosinophilic syndrome, dermatofibrosarcoma protuberans, systemic mastocytosis, as well as head and neck squamous cell carcinoma.
Chicago - A new generation of anti-cancer drugs has emerged.
Unlike conventional chemotherapies, the newer agents are able to target specific pathways or proteins involved in the malignant or cancerous behavior of cells, while sparing normal tissues. Consequently, the antitumor effect is maximized and the side effect profile is more tolerable, with minimal to no systemic or hematopoietic toxicities.
"The benefit with the newer therapies is that they may achieve a better response in terms of blocking tumors, while minimizing the adverse effects that occur with the use of chemotherapy. Furthermore, they are administered orally, as opposed to intravenously," says Mario E. Lacouture, M.D., assistant professor, department of dermatology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago.
These "targeted" anti-cancer drugs, known as kinase inhibitors, work by effectively blocking the proteins that have been implicated in numerous cancers.
According to Dr. Lacouture, this revolution with cancer drugs began with the debut of imatinib (Gleevec).
"This drug was such a remarkable breakthrough because it blocks the Bcr-Abl protein that is responsible for causing chronic myeloid leukemia. This drug is a specific inhibitor of that protein, and patients who receive this drug achieve a complete remission in up to 90 percent of cases. Side effects are minimal compared to older drugs used, and remissions can last several years, and in some cases, it is considered curative," Dr. Lacouture tells Dermatology Times.
According to Dr. Lacouture, imatinib was the first orally available drug (small molecule) that is a kinase inhibitor, approved by the Food and Drug Administration (FDA) for treatment of cancer.
Other indications for the drug include gastrointestinal stromal tumor and - importantly in dermatology - hypereosinophilic syndrome and dermatofibrosarcoma protuberans, as well as systemic mastocytosis.
"Essentially, the introduction of this drug heralded the coming of similar agents that don't target the same protein but target other proteins involved in cancer, and now there is this new generation of cancer drugs available as tablets, and that lead to spectacular results," Dr. Lacouture says.
There are two major categories of kinase inhibitors: single-targeted and multi-targeted. The single-targeted agents (the larger family) are those that block the epidermal growth factor receptor (EGFR). These drugs are also called EGFR inhibitors.
Lacouture says three drugs (erlotinib [Tarceva, OSI Pharmaceuticals; Genentech], cetuximab [Erbitux, ImClone Systems; Bristol-Meyers Squibb] and panitumumab [Vectibix, Amgen; Abgenix]) have been FDA-approved for the treatment of colorectal cancer, pancreatic cancer, and head and neck squamous cell carcinoma. Case reports have shown that patients who have psoriasis or squamous cell carcinoma on the skin also benefit from these drugs, as both diseases are partly driven by EGFR activity.
Boon with derm implications
According to Dr. Lacouture, it is imperative that dermatologists understand that these drugs offer patients potentially life-saving therapies.
In many cases, however, the therapy may need to be interrupted or discontinued due to the dermatologic side effects.
A majority of the cases, approximately 45 percent to 100 percent of patients, develop mild-to-moderate dermatologic side effects. Approximately 15 percent develop severe side effects, including papulopustular rash, periungual alterations, hair growth abnormalities, xerosis and pruritus.
Although most dermatological side effects with EGFR inhibitors are mild and usually manageable, they are associated with a decreased quality of life. In some cases they can lead to a dose interruption or discontinuation.
"Here at Northwestern, we have started the first dermatology clinic specifically geared for the management of the side effects to these medicines and to the exploration of new uses for these cancer medicines, called the SERIES clinic (skin and eye reactions to inhibitors of EGFR and kinases). This is great, because we are able to see patients right away, minimizing the possibility that these side effects can lead to the interruptions of these medicines, and (we are able to) better study these toxicities," Dr. Lacouture says.
"These drugs were used in oncology and were found to not only work in oncologic diseases but also in dermatological diseases. I believe this is the future of these drugs, as well," he says.