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New Advances in Treating
Actinic Keratoses
February 2002
When it comes to cancer, the next best thing to thoroughly effective prevention is early diagnosis and cure. Through careful research, combining the latest molecular biology techniques with your observations during practice, we now know more about this “pre-cancerous” growth than ever before. This should yield some potentially powerful preventative therapies and treatments.
In the past year, several exciting developments have built on our knowledge about how the sun causes cancer mutation in skin and how the earliest form of skin cancer, the actinic keratosis, develops.
Since we already know that mutations are a key cause of actinic keratoses, it would make sense that a compound that can reverse the mutation might be beneficial. This past spring, a landmark study was published in Lancet, which studied the use of just such a compound called T4 Endonuclease (Dimericine) in a special group of patients prone to excessive skin cancers. Its actual effect is thought to be mediated through changes in the local immunity that result from the mutation repair.
Patients in the study demonstrated a 68% decrease in the number of actinic keratoses and a 30% decrease in the number of basal cell cancers. The drug is now in phase 3 clinical trials in several southern cities to determine its effectiveness in the general population. If proven effective, this compound could help prevent the development of skin cancers by repairing the DNA mutation, functioning almost like a “morning after cream.” Although the initial effect of Dimericine is thought to be mediated through its immunologic effect, in the long-term its ability to repair cancer genes mutated by the sun may be yet another mechanism to prevent skin cancer.
Freezing Out The Cancer
Other traditional treatment methods focus on destroying the abnormal cells of actinic keratoses. The traditional method involves freezing the sunspots with liquid nitrogen, using a spray gun or a cotton-tipped applicator dipped in liquid nitrogen. Since pre-cancerous and cancerous cells are more sensitive to cold than normal cells, when frozen, the actinic keratoses tend to regress. In addition to this approach, you may use lasers or a technique that involves scraping and burning the growth.
One of the problems with these methods is that many patients can have dozens or hundreds of lesions. In addition, we know from recent research that the cancer disposition even may lurk in the cells of skin that look normal. In an effort to identify a means of treating broad areas, photodynamic therapy has progressed significantly in recent years. With photodynamic therapy it takes about 16 hours for the abnormal cells to incorporate the topical drug after which the skin is exposed to blue light which activates the drug. The drug then kills the cells by releasing oxygen radicals and results in improvement in actinic keratoses.
A more traditional approach to the management of multiple actinic keratoses is the application of 5-fluorouracil cream. The compound, a common anti-cancer drug used internally for colon cancer and others, can be used topically. Typically, the skin becomes red and irritated, but after the treatment course there is a significant reduction in actinic keratoses. The redness and irritation resolve as well. There are many different regimens that you may use to minimize the side effects of redness and erosion while maximizing effectiveness. Some dermatologists use a “pulsed” method in which the 5-fluorouracil is used only a few times a week, sometimes in combination with tretinoin.
Prevention Is Key
Although it is not known for certain what percent of actinic keratoses transform into invasive skin cancer, since we can’t predict which ones will and which ones will not, it is best to carefully monitor your patients and properly treat any lesions. But these patients can become frustrated by the frequent visits and careful monitoring, so prevention can be the best means.
Another promising area of therapy, which might provide an opportunity for treatment as well as prevention, is the use of a class of drugs that actually modify the immune system of the skin and stimulate the body’s own production of cytokines. This is thought to result in the destruction or rejection of skin cancer cells and precancerous cells of actinic keratosis. One such drug, imiquimod (Aldara), is only approved by the FDA for the treatment of genital warts. However, because of promising results in studies outside the US, many of us are now exploring the use of imiquimod in treating multiple actinic keratoses. The precise treatment regimen remains to be determined, and new variations of the compound are likely to be developed. Results of clinical trials on the use of imiquimod in actinic keratosis are expected soon. Long-term studies will be required as well. Although patients do develop redness and some irritation, if the effectiveness of imiquimod is shown to exceed that of other current therapies, the risk benefit ratio may be worth it.
For the first time, there are now a range of new options for treating, and perhaps preventing actinic keratoses. This is most important because of the cancer risk posed by this common sun-related skin condition but also of some benefit because it helps reduce what for many is also an important cosmetic problem.
When it comes to cancer, the next best thing to thoroughly effective prevention is early diagnosis and cure. Through careful research, combining the latest molecular biology techniques with your observations during practice, we now know more about this “pre-cancerous” growth than ever before. This should yield some potentially powerful preventative therapies and treatments.
In the past year, several exciting developments have built on our knowledge about how the sun causes cancer mutation in skin and how the earliest form of skin cancer, the actinic keratosis, develops.
Since we already know that mutations are a key cause of actinic keratoses, it would make sense that a compound that can reverse the mutation might be beneficial. This past spring, a landmark study was published in Lancet, which studied the use of just such a compound called T4 Endonuclease (Dimericine) in a special group of patients prone to excessive skin cancers. Its actual effect is thought to be mediated through changes in the local immunity that result from the mutation repair.
Patients in the study demonstrated a 68% decrease in the number of actinic keratoses and a 30% decrease in the number of basal cell cancers. The drug is now in phase 3 clinical trials in several southern cities to determine its effectiveness in the general population. If proven effective, this compound could help prevent the development of skin cancers by repairing the DNA mutation, functioning almost like a “morning after cream.” Although the initial effect of Dimericine is thought to be mediated through its immunologic effect, in the long-term its ability to repair cancer genes mutated by the sun may be yet another mechanism to prevent skin cancer.
Freezing Out The Cancer
Other traditional treatment methods focus on destroying the abnormal cells of actinic keratoses. The traditional method involves freezing the sunspots with liquid nitrogen, using a spray gun or a cotton-tipped applicator dipped in liquid nitrogen. Since pre-cancerous and cancerous cells are more sensitive to cold than normal cells, when frozen, the actinic keratoses tend to regress. In addition to this approach, you may use lasers or a technique that involves scraping and burning the growth.
One of the problems with these methods is that many patients can have dozens or hundreds of lesions. In addition, we know from recent research that the cancer disposition even may lurk in the cells of skin that look normal. In an effort to identify a means of treating broad areas, photodynamic therapy has progressed significantly in recent years. With photodynamic therapy it takes about 16 hours for the abnormal cells to incorporate the topical drug after which the skin is exposed to blue light which activates the drug. The drug then kills the cells by releasing oxygen radicals and results in improvement in actinic keratoses.
A more traditional approach to the management of multiple actinic keratoses is the application of 5-fluorouracil cream. The compound, a common anti-cancer drug used internally for colon cancer and others, can be used topically. Typically, the skin becomes red and irritated, but after the treatment course there is a significant reduction in actinic keratoses. The redness and irritation resolve as well. There are many different regimens that you may use to minimize the side effects of redness and erosion while maximizing effectiveness. Some dermatologists use a “pulsed” method in which the 5-fluorouracil is used only a few times a week, sometimes in combination with tretinoin.
Prevention Is Key
Although it is not known for certain what percent of actinic keratoses transform into invasive skin cancer, since we can’t predict which ones will and which ones will not, it is best to carefully monitor your patients and properly treat any lesions. But these patients can become frustrated by the frequent visits and careful monitoring, so prevention can be the best means.
Another promising area of therapy, which might provide an opportunity for treatment as well as prevention, is the use of a class of drugs that actually modify the immune system of the skin and stimulate the body’s own production of cytokines. This is thought to result in the destruction or rejection of skin cancer cells and precancerous cells of actinic keratosis. One such drug, imiquimod (Aldara), is only approved by the FDA for the treatment of genital warts. However, because of promising results in studies outside the US, many of us are now exploring the use of imiquimod in treating multiple actinic keratoses. The precise treatment regimen remains to be determined, and new variations of the compound are likely to be developed. Results of clinical trials on the use of imiquimod in actinic keratosis are expected soon. Long-term studies will be required as well. Although patients do develop redness and some irritation, if the effectiveness of imiquimod is shown to exceed that of other current therapies, the risk benefit ratio may be worth it.
For the first time, there are now a range of new options for treating, and perhaps preventing actinic keratoses. This is most important because of the cancer risk posed by this common sun-related skin condition but also of some benefit because it helps reduce what for many is also an important cosmetic problem.
When it comes to cancer, the next best thing to thoroughly effective prevention is early diagnosis and cure. Through careful research, combining the latest molecular biology techniques with your observations during practice, we now know more about this “pre-cancerous” growth than ever before. This should yield some potentially powerful preventative therapies and treatments.
In the past year, several exciting developments have built on our knowledge about how the sun causes cancer mutation in skin and how the earliest form of skin cancer, the actinic keratosis, develops.
Since we already know that mutations are a key cause of actinic keratoses, it would make sense that a compound that can reverse the mutation might be beneficial. This past spring, a landmark study was published in Lancet, which studied the use of just such a compound called T4 Endonuclease (Dimericine) in a special group of patients prone to excessive skin cancers. Its actual effect is thought to be mediated through changes in the local immunity that result from the mutation repair.
Patients in the study demonstrated a 68% decrease in the number of actinic keratoses and a 30% decrease in the number of basal cell cancers. The drug is now in phase 3 clinical trials in several southern cities to determine its effectiveness in the general population. If proven effective, this compound could help prevent the development of skin cancers by repairing the DNA mutation, functioning almost like a “morning after cream.” Although the initial effect of Dimericine is thought to be mediated through its immunologic effect, in the long-term its ability to repair cancer genes mutated by the sun may be yet another mechanism to prevent skin cancer.
Freezing Out The Cancer
Other traditional treatment methods focus on destroying the abnormal cells of actinic keratoses. The traditional method involves freezing the sunspots with liquid nitrogen, using a spray gun or a cotton-tipped applicator dipped in liquid nitrogen. Since pre-cancerous and cancerous cells are more sensitive to cold than normal cells, when frozen, the actinic keratoses tend to regress. In addition to this approach, you may use lasers or a technique that involves scraping and burning the growth.
One of the problems with these methods is that many patients can have dozens or hundreds of lesions. In addition, we know from recent research that the cancer disposition even may lurk in the cells of skin that look normal. In an effort to identify a means of treating broad areas, photodynamic therapy has progressed significantly in recent years. With photodynamic therapy it takes about 16 hours for the abnormal cells to incorporate the topical drug after which the skin is exposed to blue light which activates the drug. The drug then kills the cells by releasing oxygen radicals and results in improvement in actinic keratoses.
A more traditional approach to the management of multiple actinic keratoses is the application of 5-fluorouracil cream. The compound, a common anti-cancer drug used internally for colon cancer and others, can be used topically. Typically, the skin becomes red and irritated, but after the treatment course there is a significant reduction in actinic keratoses. The redness and irritation resolve as well. There are many different regimens that you may use to minimize the side effects of redness and erosion while maximizing effectiveness. Some dermatologists use a “pulsed” method in which the 5-fluorouracil is used only a few times a week, sometimes in combination with tretinoin.
Prevention Is Key
Although it is not known for certain what percent of actinic keratoses transform into invasive skin cancer, since we can’t predict which ones will and which ones will not, it is best to carefully monitor your patients and properly treat any lesions. But these patients can become frustrated by the frequent visits and careful monitoring, so prevention can be the best means.
Another promising area of therapy, which might provide an opportunity for treatment as well as prevention, is the use of a class of drugs that actually modify the immune system of the skin and stimulate the body’s own production of cytokines. This is thought to result in the destruction or rejection of skin cancer cells and precancerous cells of actinic keratosis. One such drug, imiquimod (Aldara), is only approved by the FDA for the treatment of genital warts. However, because of promising results in studies outside the US, many of us are now exploring the use of imiquimod in treating multiple actinic keratoses. The precise treatment regimen remains to be determined, and new variations of the compound are likely to be developed. Results of clinical trials on the use of imiquimod in actinic keratosis are expected soon. Long-term studies will be required as well. Although patients do develop redness and some irritation, if the effectiveness of imiquimod is shown to exceed that of other current therapies, the risk benefit ratio may be worth it.
For the first time, there are now a range of new options for treating, and perhaps preventing actinic keratoses. This is most important because of the cancer risk posed by this common sun-related skin condition but also of some benefit because it helps reduce what for many is also an important cosmetic problem.
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