Melanoma

Black salve is composed of various ingredients, many of which are inert; however, some black salves contain escharotics, the 2 most common are zinc chloride and bloodroot (Sanguinaria canadensis) extract. In high doses, such as those contained in most black salve products, these corrosive agents can indiscriminately damage both healthy and diseased tissue.¹ Nevertheless, many black salve products currently are advertised as safe and natural methods for curing skin cancer^2-4 or treating a variety of other skin conditions (eg, moles, warts, skin tags, boils, abscesses, bee stings, other minor wounds)^1,5 and even nondermatologic conditions such as a sore throat.⁶ Despite the information and testimonials that are widely available on the Internet, black salve use has not been validated by rigorous studies. Black salve is not regulated by the US Food and Drug Administration, resulting in poor quality control and inconsistent user instructions. We report the case of application of black salve to a biopsy site of a compound nevus with moderate atypia that resulted in the formation of a dermatitis plaque with subsequent scarring and basal layer pigmentation.

Case Report

A 35-year-old woman with a family history of melanoma presented for follow-up of a compound nevus with moderate atypia on the right anterior thigh that had been biopsied 6 months prior. Complete excision of the lesion was recommended at the initial presentation but was not performed due to scheduling conflicts. The patient reported applying black salve to the biopsy site and also to the left thigh 3 months later. There was no reaction on the left thigh after one 24-hour application of black salve, but an area around the biopsy site on the right thigh became thickened and irritated with superficial erosion of the skin following 2 applications of black salve, each of 24 hours’ duration. Physical examination revealed a granulomatous plaque at the biopsy site that was approximately 5 cm in diameter (Figure 1A). One year later the lesion had completely healed (Figure 1B) and a biopsy revealed scarring with basal layer pigmentation (Figure 2).

Figure 1. A 5-cm granulomatous reaction surrounding a biopsy site on the right anterior thigh 3 months after application of black salve (A). One year later, the lesion had completely healed (B).					Figure 2. A biopsy one year following application of black salve demonstrated scarring with basal layer pigmentation (H&E, original magnification ×4).

Comment

A Web search using the term black salve yields a large number of products labeled as skin cancer salves, many showing glowing reviews and some being sold by major US retailers. The ingredients in black salves often vary in the innocuous substances they contain, but most products include the escharotics zinc chloride and bloodroot extract, which is derived from the plant S canadensis.^1,3 For example, the ingredients of one popular black salve product include zinc chloride, chaparral (active ingredient is nordihydroguaiaretic acid), graviola leaf extract, oleander leaf extract, bloodroot extract, and glycerine,⁷ while another product includes bloodroot extract, zinc chloride, chaparral, cayenne pepper, red clover, birch bark, dimethyl sulfoxide, and burdock root.⁴

Bloodroot extract’s antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory effects derive from its benzylisoquinoline alkaloids including sanguinarine, allocryptopine, berberine, coptisine, protopine, and stylopine.^3,8 Bloodroot extract possesses some degree of tumoricidal potency, with one study finding that it selectively targets cancer cells.⁹ However, this differential response is seen only at low doses and not at the high concentrations contained in most black salve products.¹ According to fluorometric assays, sanguinarine is not selective for tumor cells and therefore damages healthy tissue in addition to the unwanted lesions.^6,10,11 The US Food and Drug Administration includes black salve products on its list of fake cancer cures that consumers should avoid.¹² Reports of extensive damage from black salve use include skin ulceration^2,10 and complete loss of a naris¹ and nasal ala.⁵ Our case suggests the possible association between black salve use and an irritant reaction and erosion of the skin.

Furthermore, reliance on black salve alone in the treatment of skin cancer poses the threat of recurrence or metastasis of cancer because there is no way to know if the salve completely removed the cancer without a biopsy. Self-treatment can delay more effective therapy and may require further treatments.

Black salve should be subject to standarddrug regulations and its use discouraged by dermatologists due to the associated harmful effects and the availability of safer treatments. To better treat and inform their patients, dermatologists should be aware that patients may be attracted to alternative treatments such as black salves.

Black salve is composed of various ingredients, many of which are inert; however, some black salves contain escharotics, the 2 most common are zinc chloride and bloodroot (Sanguinaria canadensis) extract. In high doses, such as those contained in most black salve products, these corrosive agents can indiscriminately damage both healthy and diseased tissue.¹ Nevertheless, many black salve products currently are advertised as safe and natural methods for curing skin cancer^2-4 or treating a variety of other skin conditions (eg, moles, warts, skin tags, boils, abscesses, bee stings, other minor wounds)^1,5 and even nondermatologic conditions such as a sore throat.⁶ Despite the information and testimonials that are widely available on the Internet, black salve use has not been validated by rigorous studies. Black salve is not regulated by the US Food and Drug Administration, resulting in poor quality control and inconsistent user instructions. We report the case of application of black salve to a biopsy site of a compound nevus with moderate atypia that resulted in the formation of a dermatitis plaque with subsequent scarring and basal layer pigmentation.

Case Report

A 35-year-old woman with a family history of melanoma presented for follow-up of a compound nevus with moderate atypia on the right anterior thigh that had been biopsied 6 months prior. Complete excision of the lesion was recommended at the initial presentation but was not performed due to scheduling conflicts. The patient reported applying black salve to the biopsy site and also to the left thigh 3 months later. There was no reaction on the left thigh after one 24-hour application of black salve, but an area around the biopsy site on the right thigh became thickened and irritated with superficial erosion of the skin following 2 applications of black salve, each of 24 hours’ duration. Physical examination revealed a granulomatous plaque at the biopsy site that was approximately 5 cm in diameter (Figure 1A). One year later the lesion had completely healed (Figure 1B) and a biopsy revealed scarring with basal layer pigmentation (Figure 2).

Figure 1. A 5-cm granulomatous reaction surrounding a biopsy site on the right anterior thigh 3 months after application of black salve (A). One year later, the lesion had completely healed (B).					Figure 2. A biopsy one year following application of black salve demonstrated scarring with basal layer pigmentation (H&E, original magnification ×4).

Comment

A Web search using the term black salve yields a large number of products labeled as skin cancer salves, many showing glowing reviews and some being sold by major US retailers. The ingredients in black salves often vary in the innocuous substances they contain, but most products include the escharotics zinc chloride and bloodroot extract, which is derived from the plant S canadensis.^1,3 For example, the ingredients of one popular black salve product include zinc chloride, chaparral (active ingredient is nordihydroguaiaretic acid), graviola leaf extract, oleander leaf extract, bloodroot extract, and glycerine,⁷ while another product includes bloodroot extract, zinc chloride, chaparral, cayenne pepper, red clover, birch bark, dimethyl sulfoxide, and burdock root.⁴

Bloodroot extract’s antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory effects derive from its benzylisoquinoline alkaloids including sanguinarine, allocryptopine, berberine, coptisine, protopine, and stylopine.^3,8 Bloodroot extract possesses some degree of tumoricidal potency, with one study finding that it selectively targets cancer cells.⁹ However, this differential response is seen only at low doses and not at the high concentrations contained in most black salve products.¹ According to fluorometric assays, sanguinarine is not selective for tumor cells and therefore damages healthy tissue in addition to the unwanted lesions.^6,10,11 The US Food and Drug Administration includes black salve products on its list of fake cancer cures that consumers should avoid.¹² Reports of extensive damage from black salve use include skin ulceration^2,10 and complete loss of a naris¹ and nasal ala.⁵ Our case suggests the possible association between black salve use and an irritant reaction and erosion of the skin.

Furthermore, reliance on black salve alone in the treatment of skin cancer poses the threat of recurrence or metastasis of cancer because there is no way to know if the salve completely removed the cancer without a biopsy. Self-treatment can delay more effective therapy and may require further treatments.

Black salve should be subject to standarddrug regulations and its use discouraged by dermatologists due to the associated harmful effects and the availability of safer treatments. To better treat and inform their patients, dermatologists should be aware that patients may be attracted to alternative treatments such as black salves.

Black salve is composed of various ingredients, many of which are inert; however, some black salves contain escharotics, the 2 most common are zinc chloride and bloodroot (Sanguinaria canadensis) extract. In high doses, such as those contained in most black salve products, these corrosive agents can indiscriminately damage both healthy and diseased tissue.¹ Nevertheless, many black salve products currently are advertised as safe and natural methods for curing skin cancer^2-4 or treating a variety of other skin conditions (eg, moles, warts, skin tags, boils, abscesses, bee stings, other minor wounds)^1,5 and even nondermatologic conditions such as a sore throat.⁶ Despite the information and testimonials that are widely available on the Internet, black salve use has not been validated by rigorous studies. Black salve is not regulated by the US Food and Drug Administration, resulting in poor quality control and inconsistent user instructions. We report the case of application of black salve to a biopsy site of a compound nevus with moderate atypia that resulted in the formation of a dermatitis plaque with subsequent scarring and basal layer pigmentation.

Case Report

A 35-year-old woman with a family history of melanoma presented for follow-up of a compound nevus with moderate atypia on the right anterior thigh that had been biopsied 6 months prior. Complete excision of the lesion was recommended at the initial presentation but was not performed due to scheduling conflicts. The patient reported applying black salve to the biopsy site and also to the left thigh 3 months later. There was no reaction on the left thigh after one 24-hour application of black salve, but an area around the biopsy site on the right thigh became thickened and irritated with superficial erosion of the skin following 2 applications of black salve, each of 24 hours’ duration. Physical examination revealed a granulomatous plaque at the biopsy site that was approximately 5 cm in diameter (Figure 1A). One year later the lesion had completely healed (Figure 1B) and a biopsy revealed scarring with basal layer pigmentation (Figure 2).

Figure 1. A 5-cm granulomatous reaction surrounding a biopsy site on the right anterior thigh 3 months after application of black salve (A). One year later, the lesion had completely healed (B).					Figure 2. A biopsy one year following application of black salve demonstrated scarring with basal layer pigmentation (H&E, original magnification ×4).

Comment

A Web search using the term black salve yields a large number of products labeled as skin cancer salves, many showing glowing reviews and some being sold by major US retailers. The ingredients in black salves often vary in the innocuous substances they contain, but most products include the escharotics zinc chloride and bloodroot extract, which is derived from the plant S canadensis.^1,3 For example, the ingredients of one popular black salve product include zinc chloride, chaparral (active ingredient is nordihydroguaiaretic acid), graviola leaf extract, oleander leaf extract, bloodroot extract, and glycerine,⁷ while another product includes bloodroot extract, zinc chloride, chaparral, cayenne pepper, red clover, birch bark, dimethyl sulfoxide, and burdock root.⁴

Bloodroot extract’s antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory effects derive from its benzylisoquinoline alkaloids including sanguinarine, allocryptopine, berberine, coptisine, protopine, and stylopine.^3,8 Bloodroot extract possesses some degree of tumoricidal potency, with one study finding that it selectively targets cancer cells.⁹ However, this differential response is seen only at low doses and not at the high concentrations contained in most black salve products.¹ According to fluorometric assays, sanguinarine is not selective for tumor cells and therefore damages healthy tissue in addition to the unwanted lesions.^6,10,11 The US Food and Drug Administration includes black salve products on its list of fake cancer cures that consumers should avoid.¹² Reports of extensive damage from black salve use include skin ulceration^2,10 and complete loss of a naris¹ and nasal ala.⁵ Our case suggests the possible association between black salve use and an irritant reaction and erosion of the skin.

Furthermore, reliance on black salve alone in the treatment of skin cancer poses the threat of recurrence or metastasis of cancer because there is no way to know if the salve completely removed the cancer without a biopsy. Self-treatment can delay more effective therapy and may require further treatments.

Black salve should be subject to standarddrug regulations and its use discouraged by dermatologists due to the associated harmful effects and the availability of safer treatments. To better treat and inform their patients, dermatologists should be aware that patients may be attracted to alternative treatments such as black salves.

“An apple a day keeps the doctor away,” and coffee each day keeps the melanoma away. A recent analysis of data by Loftfield et al from a food frequency questionnaire published online on January 20 in the Journal of the National Cancer Institute demonstrated that caffeinated coffee intake was inversely associated with melanoma. Specifically, consuming 4 or more cups of caffeinated coffee each day was found to decrease the risk for melanoma by 20%.

The authors’ reference groups were derived from a National Institutes of Health–AARP prospective cohort diet and health study that commenced in 1995 to 1996 and concluded on December 31, 2006. They observed that the lower risk for melanoma was only associated with caffeinated coffee. Unexpectedly, they also observed that caffeinated coffee drinking only decreased the risk for melanoma but not melanoma in situ.

There is scientific evidence that coffee has a role in decreasing UVB-induced carcinogenesis. Caffeine (both orally and topically) inhibits UVB-induced carcinogenesis by absorbing UV radiation. Also, 5-O-caffeoylquinic acid (the major chlorogenic acid in coffee) and its metabolite caffeic acid inhibit cyclooxygenase 2 expression, which is overexpressed in human melanoma cells and in response to UVB exposure. In addition to caffeine, coffee also contains several bioactive compounds: diterpenes, polyphenols, and trigonelline. Topical diterpenes inhibit inflammation in epidermal cells. During coffee roasting, trigonelline generates nicotinic acid and nicotinamide, both of which are protective against UVB-induced skin carcinogenesis in mice and UVB-induced immunosuppression in both humans and mice.

What’s the issue?

According to an article in The Washington Post, the “apple” adage originated in the 1860s; the original phrase was “Eat an apple on going to bed, and you’ll keep the doctor from earning his bread,” which evolved to “An apple a day, no doctor to pay,” then “An apple a day sends the doctor away” before the current version was first used in 1922. As one who enjoys having a cup of caffeinated coffee next to my computer in the office or at home, I can easily welcome the prospect of a few additional cups each day to prevent melanoma. And, as advocates for a possible benefit to our patients’ better health, should we should provide complimentary caffeinated coffee in our office waiting rooms to encourage our dermatology patients to decrease their risk for developing melanoma?

We want to know your views! Tell us what you think.

“An apple a day keeps the doctor away,” and coffee each day keeps the melanoma away. A recent analysis of data by Loftfield et al from a food frequency questionnaire published online on January 20 in the Journal of the National Cancer Institute demonstrated that caffeinated coffee intake was inversely associated with melanoma. Specifically, consuming 4 or more cups of caffeinated coffee each day was found to decrease the risk for melanoma by 20%.

The authors’ reference groups were derived from a National Institutes of Health–AARP prospective cohort diet and health study that commenced in 1995 to 1996 and concluded on December 31, 2006. They observed that the lower risk for melanoma was only associated with caffeinated coffee. Unexpectedly, they also observed that caffeinated coffee drinking only decreased the risk for melanoma but not melanoma in situ.

There is scientific evidence that coffee has a role in decreasing UVB-induced carcinogenesis. Caffeine (both orally and topically) inhibits UVB-induced carcinogenesis by absorbing UV radiation. Also, 5-O-caffeoylquinic acid (the major chlorogenic acid in coffee) and its metabolite caffeic acid inhibit cyclooxygenase 2 expression, which is overexpressed in human melanoma cells and in response to UVB exposure. In addition to caffeine, coffee also contains several bioactive compounds: diterpenes, polyphenols, and trigonelline. Topical diterpenes inhibit inflammation in epidermal cells. During coffee roasting, trigonelline generates nicotinic acid and nicotinamide, both of which are protective against UVB-induced skin carcinogenesis in mice and UVB-induced immunosuppression in both humans and mice.

What’s the issue?

According to an article in The Washington Post, the “apple” adage originated in the 1860s; the original phrase was “Eat an apple on going to bed, and you’ll keep the doctor from earning his bread,” which evolved to “An apple a day, no doctor to pay,” then “An apple a day sends the doctor away” before the current version was first used in 1922. As one who enjoys having a cup of caffeinated coffee next to my computer in the office or at home, I can easily welcome the prospect of a few additional cups each day to prevent melanoma. And, as advocates for a possible benefit to our patients’ better health, should we should provide complimentary caffeinated coffee in our office waiting rooms to encourage our dermatology patients to decrease their risk for developing melanoma?

We want to know your views! Tell us what you think.

“An apple a day keeps the doctor away,” and coffee each day keeps the melanoma away. A recent analysis of data by Loftfield et al from a food frequency questionnaire published online on January 20 in the Journal of the National Cancer Institute demonstrated that caffeinated coffee intake was inversely associated with melanoma. Specifically, consuming 4 or more cups of caffeinated coffee each day was found to decrease the risk for melanoma by 20%.

The authors’ reference groups were derived from a National Institutes of Health–AARP prospective cohort diet and health study that commenced in 1995 to 1996 and concluded on December 31, 2006. They observed that the lower risk for melanoma was only associated with caffeinated coffee. Unexpectedly, they also observed that caffeinated coffee drinking only decreased the risk for melanoma but not melanoma in situ.

There is scientific evidence that coffee has a role in decreasing UVB-induced carcinogenesis. Caffeine (both orally and topically) inhibits UVB-induced carcinogenesis by absorbing UV radiation. Also, 5-O-caffeoylquinic acid (the major chlorogenic acid in coffee) and its metabolite caffeic acid inhibit cyclooxygenase 2 expression, which is overexpressed in human melanoma cells and in response to UVB exposure. In addition to caffeine, coffee also contains several bioactive compounds: diterpenes, polyphenols, and trigonelline. Topical diterpenes inhibit inflammation in epidermal cells. During coffee roasting, trigonelline generates nicotinic acid and nicotinamide, both of which are protective against UVB-induced skin carcinogenesis in mice and UVB-induced immunosuppression in both humans and mice.

What’s the issue?

According to an article in The Washington Post, the “apple” adage originated in the 1860s; the original phrase was “Eat an apple on going to bed, and you’ll keep the doctor from earning his bread,” which evolved to “An apple a day, no doctor to pay,” then “An apple a day sends the doctor away” before the current version was first used in 1922. As one who enjoys having a cup of caffeinated coffee next to my computer in the office or at home, I can easily welcome the prospect of a few additional cups each day to prevent melanoma. And, as advocates for a possible benefit to our patients’ better health, should we should provide complimentary caffeinated coffee in our office waiting rooms to encourage our dermatology patients to decrease their risk for developing melanoma?

We want to know your views! Tell us what you think.

CHICAGO – It’s getting very personal in oncology, and that’s a very good thing.

At the annual meeting of the American Society of Clinical Oncology, major cancer organizations announced new precision medicine initiatives that will attempt to match patients who have advanced cancers with the best available therapies based not on the location or histologic subtypes of their tumors, but on specific molecular abnormalities.

The National Cancer Institute’s Molecular Analysis for Therapy Choice (NCI-MATCH) trial will begin enrolling patients in July 2015. The study’s objective is “to understand the relative efficacy of the same therapy applied to oncogene-defined subsets across the entire cancer population as defined by site of origin or tumor histology,” said co–principal investigator Dr. Keith T. Flaherty of Harvard Medical School, Boston.

“This is the beginning, not the end, in terms of how we think about applying these therapies,” he said at a briefing that was held to announce the start of trial enrollment and a second initiative – the Targeted Agent and Profiling Utilization Registry (TAPUR) Study – by ASCO in cooperation with major pharmaceutical companies.

NCI-MATCH

NCI-MATCH is a phase II trial that will be operated through the National Clinical Trials Network. Oncologists at participating centers throughout the United States can enroll patients aged 18 years and older who have solid tumors or lymphomas that have relapsed or are refractory to conventional therapy, or who have a type of cancer for which no effective, consensus-based therapy is available.

Investigators plan to screen 3,000 patients initially, with the goal of enrolling 1,000 patients distributed among several substudies that will be evaluating specific drugs against specific molecular targets.

Patients will undergo biopsy at study entry, and their tumors will be subjected to genomic analysis to detect specific, targetable molecular abnormalities.

If a patient has a specific abnormality that is being explored in a current substudy, that patient will be further evaluated to determine whether he or she meets the eligibility criteria for that trial arm. Once enrolled, patients can remain on therapy until disease progression. The therapies will include both currently marketed agents and investigational therapies contributed by drug companies. Most of the trial arms will explore monotherapy with a targeted agent, but a few may investigate combinations which have accumulated enough safety and efficacy data to suggest that they might work against a specific molecular target.

The primary endpoint will be overall response rate, with a secondary endpoint of 6-month progression-free survival (PFS).

“This holds promise to bring faster cures to millions of Americans who so desperately need them,” ASCO past president Dr. Clifford A. Hudis said at the briefing.

TAPUR Trial

In cooperation with major pharmaceutical manufacturers (currently five, with more expected to sign on), ASCO has initiated a study designed to help answer the question, “I’ve got the tumor genome – now what do I do with it?”

The goal of the TAPUR trial, says ASCO Chief Medical Officer Dr. Richard Schilsky, is “to learn from the real world practice of prescribing targeted therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be a drug target.”

The primary objectives are to describe the antitumor activity and toxicity profiles of targeted therapies, and to help patients get access to Food and Drug Administration–approved agents from which they may be able to benefit.

The trial will enroll patients with advanced solid tumors, B-cell non-Hodgkin’s lymphomas, and multiple myelomas for which there are no standard therapies. The patients must have adequate organ function and good performance status (0-2).

Patients will be matched by their personal physicians to specific therapies, if such a match exists; otherwise, they will be treated at the physician’s discretion.

The primary endpoint of the study will be overall response rates by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints will be PFS, OS, time on treatment, grade 3 or greater adverse events, and serious adverse event. The investigators plan to begin patient enrollment in the fourth quarter of 2015.

Current industry partners include AstraZeneca, Bristol Myers Squibb, Eli Lilly, Genentech, and Pfizer.

The NCI-MATCH study is funded by the National Institutes of Health. Dr. Flaherty has received NIH research grants. Dr. Hudis disclosed ties to AstraZeneca, Sanofi-Aventis, Amgen, Bristol-Myers Squibb, Genentech, Eli Lilly, Novartis, Ortho Biotech, Pfizer, and Roche. Dr. Schilsky disclosed no relevant conflicts of interest.

CHICAGO – It’s getting very personal in oncology, and that’s a very good thing.

At the annual meeting of the American Society of Clinical Oncology, major cancer organizations announced new precision medicine initiatives that will attempt to match patients who have advanced cancers with the best available therapies based not on the location or histologic subtypes of their tumors, but on specific molecular abnormalities.

The National Cancer Institute’s Molecular Analysis for Therapy Choice (NCI-MATCH) trial will begin enrolling patients in July 2015. The study’s objective is “to understand the relative efficacy of the same therapy applied to oncogene-defined subsets across the entire cancer population as defined by site of origin or tumor histology,” said co–principal investigator Dr. Keith T. Flaherty of Harvard Medical School, Boston.

“This is the beginning, not the end, in terms of how we think about applying these therapies,” he said at a briefing that was held to announce the start of trial enrollment and a second initiative – the Targeted Agent and Profiling Utilization Registry (TAPUR) Study – by ASCO in cooperation with major pharmaceutical companies.

NCI-MATCH

NCI-MATCH is a phase II trial that will be operated through the National Clinical Trials Network. Oncologists at participating centers throughout the United States can enroll patients aged 18 years and older who have solid tumors or lymphomas that have relapsed or are refractory to conventional therapy, or who have a type of cancer for which no effective, consensus-based therapy is available.

Investigators plan to screen 3,000 patients initially, with the goal of enrolling 1,000 patients distributed among several substudies that will be evaluating specific drugs against specific molecular targets.

Patients will undergo biopsy at study entry, and their tumors will be subjected to genomic analysis to detect specific, targetable molecular abnormalities.

If a patient has a specific abnormality that is being explored in a current substudy, that patient will be further evaluated to determine whether he or she meets the eligibility criteria for that trial arm. Once enrolled, patients can remain on therapy until disease progression. The therapies will include both currently marketed agents and investigational therapies contributed by drug companies. Most of the trial arms will explore monotherapy with a targeted agent, but a few may investigate combinations which have accumulated enough safety and efficacy data to suggest that they might work against a specific molecular target.

The primary endpoint will be overall response rate, with a secondary endpoint of 6-month progression-free survival (PFS).

“This holds promise to bring faster cures to millions of Americans who so desperately need them,” ASCO past president Dr. Clifford A. Hudis said at the briefing.

TAPUR Trial

In cooperation with major pharmaceutical manufacturers (currently five, with more expected to sign on), ASCO has initiated a study designed to help answer the question, “I’ve got the tumor genome – now what do I do with it?”

The goal of the TAPUR trial, says ASCO Chief Medical Officer Dr. Richard Schilsky, is “to learn from the real world practice of prescribing targeted therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be a drug target.”

The primary objectives are to describe the antitumor activity and toxicity profiles of targeted therapies, and to help patients get access to Food and Drug Administration–approved agents from which they may be able to benefit.

The trial will enroll patients with advanced solid tumors, B-cell non-Hodgkin’s lymphomas, and multiple myelomas for which there are no standard therapies. The patients must have adequate organ function and good performance status (0-2).

Patients will be matched by their personal physicians to specific therapies, if such a match exists; otherwise, they will be treated at the physician’s discretion.

The primary endpoint of the study will be overall response rates by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints will be PFS, OS, time on treatment, grade 3 or greater adverse events, and serious adverse event. The investigators plan to begin patient enrollment in the fourth quarter of 2015.

Current industry partners include AstraZeneca, Bristol Myers Squibb, Eli Lilly, Genentech, and Pfizer.

The NCI-MATCH study is funded by the National Institutes of Health. Dr. Flaherty has received NIH research grants. Dr. Hudis disclosed ties to AstraZeneca, Sanofi-Aventis, Amgen, Bristol-Myers Squibb, Genentech, Eli Lilly, Novartis, Ortho Biotech, Pfizer, and Roche. Dr. Schilsky disclosed no relevant conflicts of interest.

CHICAGO – It’s getting very personal in oncology, and that’s a very good thing.

At the annual meeting of the American Society of Clinical Oncology, major cancer organizations announced new precision medicine initiatives that will attempt to match patients who have advanced cancers with the best available therapies based not on the location or histologic subtypes of their tumors, but on specific molecular abnormalities.

The National Cancer Institute’s Molecular Analysis for Therapy Choice (NCI-MATCH) trial will begin enrolling patients in July 2015. The study’s objective is “to understand the relative efficacy of the same therapy applied to oncogene-defined subsets across the entire cancer population as defined by site of origin or tumor histology,” said co–principal investigator Dr. Keith T. Flaherty of Harvard Medical School, Boston.

“This is the beginning, not the end, in terms of how we think about applying these therapies,” he said at a briefing that was held to announce the start of trial enrollment and a second initiative – the Targeted Agent and Profiling Utilization Registry (TAPUR) Study – by ASCO in cooperation with major pharmaceutical companies.

NCI-MATCH

NCI-MATCH is a phase II trial that will be operated through the National Clinical Trials Network. Oncologists at participating centers throughout the United States can enroll patients aged 18 years and older who have solid tumors or lymphomas that have relapsed or are refractory to conventional therapy, or who have a type of cancer for which no effective, consensus-based therapy is available.

Investigators plan to screen 3,000 patients initially, with the goal of enrolling 1,000 patients distributed among several substudies that will be evaluating specific drugs against specific molecular targets.

Patients will undergo biopsy at study entry, and their tumors will be subjected to genomic analysis to detect specific, targetable molecular abnormalities.

If a patient has a specific abnormality that is being explored in a current substudy, that patient will be further evaluated to determine whether he or she meets the eligibility criteria for that trial arm. Once enrolled, patients can remain on therapy until disease progression. The therapies will include both currently marketed agents and investigational therapies contributed by drug companies. Most of the trial arms will explore monotherapy with a targeted agent, but a few may investigate combinations which have accumulated enough safety and efficacy data to suggest that they might work against a specific molecular target.

The primary endpoint will be overall response rate, with a secondary endpoint of 6-month progression-free survival (PFS).

“This holds promise to bring faster cures to millions of Americans who so desperately need them,” ASCO past president Dr. Clifford A. Hudis said at the briefing.

TAPUR Trial

In cooperation with major pharmaceutical manufacturers (currently five, with more expected to sign on), ASCO has initiated a study designed to help answer the question, “I’ve got the tumor genome – now what do I do with it?”

The goal of the TAPUR trial, says ASCO Chief Medical Officer Dr. Richard Schilsky, is “to learn from the real world practice of prescribing targeted therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be a drug target.”

The primary objectives are to describe the antitumor activity and toxicity profiles of targeted therapies, and to help patients get access to Food and Drug Administration–approved agents from which they may be able to benefit.

The trial will enroll patients with advanced solid tumors, B-cell non-Hodgkin’s lymphomas, and multiple myelomas for which there are no standard therapies. The patients must have adequate organ function and good performance status (0-2).

Patients will be matched by their personal physicians to specific therapies, if such a match exists; otherwise, they will be treated at the physician’s discretion.

The primary endpoint of the study will be overall response rates by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints will be PFS, OS, time on treatment, grade 3 or greater adverse events, and serious adverse event. The investigators plan to begin patient enrollment in the fourth quarter of 2015.

Current industry partners include AstraZeneca, Bristol Myers Squibb, Eli Lilly, Genentech, and Pfizer.

The NCI-MATCH study is funded by the National Institutes of Health. Dr. Flaherty has received NIH research grants. Dr. Hudis disclosed ties to AstraZeneca, Sanofi-Aventis, Amgen, Bristol-Myers Squibb, Genentech, Eli Lilly, Novartis, Ortho Biotech, Pfizer, and Roche. Dr. Schilsky disclosed no relevant conflicts of interest.

Nicotinamide, an inexpensive, over-the-counter form of vitamin B₃, is safe and efficacious for the chemoprevention of nonmelanoma skin cancer in patients at high risk, according to data from the Australian Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) Study.

Results reported in a press briefing held before the annual meeting of the American Society of Clinical Oncology showed that patients taking nicotinamide were about one-fourth less likely than peers taking a placebo to develop new basal cell and squamous cell skin cancers. They also had a smaller reduction in new actinic keratoses.

“Nicotinamide, vitamin B₃, significantly reduced nonmelanoma skin cancers and keratoses in just 12 months in a group of pretty high-risk patients. It’s safe, it’s almost obscenely inexpensive, and it’s already widely commercially available, so this one’s ready to go straight into the clinic,” commented senior investigator Dr. Diona Damian, professor of dermatology at the University of Sydney.

She cautioned that the results apply only to the population studied: adults who had experienced two or more nonmelanoma skin cancers in the past 5 years.

“These are the people we’d be recommending it for – people who have already got a skin cancer track record. It’s not something that we’d recommend at this stage for the general population,” she said. Likewise, the findings do not speak to patients at the other end of the spectrum who are in treatment for advanced or metastatic skin cancer, as they also were excluded.

That said, the researchers are planning additional studies in other populations, such patients who are at high risk because they have immunosuppression, according to Dr. Damian.

“We still need the overall skin cancer prevention strategies of sun-safe behavior, sunscreen, and regular skin surveillance,” she stressed, “but we now have an additional exciting opportunity for affordable skin cancer chemoprevention which we can instantly translate into clinical practice.”

Dr. Peter Paul Yu, ASCO President and a medical oncologist and hematologist who is director of cancer research at the Palo Alto Medical Foundation, Sunnyvale, Calif., commented, “This is a very exciting prevention trial. We all know that we clamor for preventing rather than treating diseases, and this is a major advance for us.”

Exposure to ultraviolet light packs a one-two punch to the skin, both damaging cellular DNA and suppressing the skin’s immune response, according to Dr. Damian. The investigators opted to test nicotinamide as it counters both of these events.

The 386 patients in ONTRAC had heavily sun damaged skin, with a mean of 8 nonmelanoma skin cancers in the past 5 years and 50 keratoses at baseline. They were randomized evenly to receive nicotinamide (500 mg twice daily) or placebo for 12 months.

Results showed that the average number of new nonmelanoma skin cancers per patient during the treatment period was 1.77 in the nicotinamide group and 2.42 in the placebo group. The difference translated to a 23% lower rate of new cancers with the vitamin.

“There were comparable reductions seen for both basal and squamous cell carcinomas,” Dr. Damian noted. “Interestingly, this reduction in skin cancers seemed to start as early as the first 3-month visit. And then when people stopped taking their tablets after 12 months, the benefit was no longer seen. In other words, you need to continue taking the tablets in order for them to be effective.”

The nicotinamide group also had a roughly 15% lower rate of new actinic keratoses, compared with the placebo group.

“Nicotinamide was very well tolerated. There was no difference in adverse events, blood parameters, or blood pressure in the two arms” of the study, reported Dr. Damian. She stressed that it is critically important to distinguish nicotinamide from niacin (nicotinic acid), another form of vitamin B₃ that has a host of side effects such as headache and flushing.

“One of the great things about [nicotinamide] is that it really has hardly any drug interactions, which means that elderly patients who may be taking a whole cocktail of medications for their heart disease and their hypertension, and whatever else, the nicotinamide won’t interact with those,” she added.

Some evidence also has shown nonsteroidal anti-inflammatory drugs to reduce the risk of skin cancer. “The advantage of nicotinamide is that it doesn’t have the potential gastrointestinal bleeding or renal side effects of nonsteroidals, so it may be suitable for a group of people who aren’t suitable for taking nonsteroidals,” she said. “In our ONTRAC study, we didn’t find synergy or additional benefit in people who were coincidentally taking nonsteroidals for other indications.”

The trial’s results should be generalizable to similar high-risk patients in less sunny parts of the world, Dr. Damian said. “If their skin has shown that degree of damage to get skin cancer, then we suspect nicotinamide would offer benefits to them as well.”

Dr. Damian disclosed no relevant conflicts of interest. The study was funded by the National Health & Medical Research Council.

Nicotinamide, an inexpensive, over-the-counter form of vitamin B₃, is safe and efficacious for the chemoprevention of nonmelanoma skin cancer in patients at high risk, according to data from the Australian Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) Study.

Results reported in a press briefing held before the annual meeting of the American Society of Clinical Oncology showed that patients taking nicotinamide were about one-fourth less likely than peers taking a placebo to develop new basal cell and squamous cell skin cancers. They also had a smaller reduction in new actinic keratoses.

“Nicotinamide, vitamin B₃, significantly reduced nonmelanoma skin cancers and keratoses in just 12 months in a group of pretty high-risk patients. It’s safe, it’s almost obscenely inexpensive, and it’s already widely commercially available, so this one’s ready to go straight into the clinic,” commented senior investigator Dr. Diona Damian, professor of dermatology at the University of Sydney.

She cautioned that the results apply only to the population studied: adults who had experienced two or more nonmelanoma skin cancers in the past 5 years.

“These are the people we’d be recommending it for – people who have already got a skin cancer track record. It’s not something that we’d recommend at this stage for the general population,” she said. Likewise, the findings do not speak to patients at the other end of the spectrum who are in treatment for advanced or metastatic skin cancer, as they also were excluded.

That said, the researchers are planning additional studies in other populations, such patients who are at high risk because they have immunosuppression, according to Dr. Damian.

“We still need the overall skin cancer prevention strategies of sun-safe behavior, sunscreen, and regular skin surveillance,” she stressed, “but we now have an additional exciting opportunity for affordable skin cancer chemoprevention which we can instantly translate into clinical practice.”

Dr. Peter Paul Yu, ASCO President and a medical oncologist and hematologist who is director of cancer research at the Palo Alto Medical Foundation, Sunnyvale, Calif., commented, “This is a very exciting prevention trial. We all know that we clamor for preventing rather than treating diseases, and this is a major advance for us.”

Exposure to ultraviolet light packs a one-two punch to the skin, both damaging cellular DNA and suppressing the skin’s immune response, according to Dr. Damian. The investigators opted to test nicotinamide as it counters both of these events.

The 386 patients in ONTRAC had heavily sun damaged skin, with a mean of 8 nonmelanoma skin cancers in the past 5 years and 50 keratoses at baseline. They were randomized evenly to receive nicotinamide (500 mg twice daily) or placebo for 12 months.

Results showed that the average number of new nonmelanoma skin cancers per patient during the treatment period was 1.77 in the nicotinamide group and 2.42 in the placebo group. The difference translated to a 23% lower rate of new cancers with the vitamin.

“There were comparable reductions seen for both basal and squamous cell carcinomas,” Dr. Damian noted. “Interestingly, this reduction in skin cancers seemed to start as early as the first 3-month visit. And then when people stopped taking their tablets after 12 months, the benefit was no longer seen. In other words, you need to continue taking the tablets in order for them to be effective.”

The nicotinamide group also had a roughly 15% lower rate of new actinic keratoses, compared with the placebo group.

“Nicotinamide was very well tolerated. There was no difference in adverse events, blood parameters, or blood pressure in the two arms” of the study, reported Dr. Damian. She stressed that it is critically important to distinguish nicotinamide from niacin (nicotinic acid), another form of vitamin B₃ that has a host of side effects such as headache and flushing.

“One of the great things about [nicotinamide] is that it really has hardly any drug interactions, which means that elderly patients who may be taking a whole cocktail of medications for their heart disease and their hypertension, and whatever else, the nicotinamide won’t interact with those,” she added.

Some evidence also has shown nonsteroidal anti-inflammatory drugs to reduce the risk of skin cancer. “The advantage of nicotinamide is that it doesn’t have the potential gastrointestinal bleeding or renal side effects of nonsteroidals, so it may be suitable for a group of people who aren’t suitable for taking nonsteroidals,” she said. “In our ONTRAC study, we didn’t find synergy or additional benefit in people who were coincidentally taking nonsteroidals for other indications.”

The trial’s results should be generalizable to similar high-risk patients in less sunny parts of the world, Dr. Damian said. “If their skin has shown that degree of damage to get skin cancer, then we suspect nicotinamide would offer benefits to them as well.”

Dr. Damian disclosed no relevant conflicts of interest. The study was funded by the National Health & Medical Research Council.

Nicotinamide, an inexpensive, over-the-counter form of vitamin B₃, is safe and efficacious for the chemoprevention of nonmelanoma skin cancer in patients at high risk, according to data from the Australian Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) Study.

Results reported in a press briefing held before the annual meeting of the American Society of Clinical Oncology showed that patients taking nicotinamide were about one-fourth less likely than peers taking a placebo to develop new basal cell and squamous cell skin cancers. They also had a smaller reduction in new actinic keratoses.

“Nicotinamide, vitamin B₃, significantly reduced nonmelanoma skin cancers and keratoses in just 12 months in a group of pretty high-risk patients. It’s safe, it’s almost obscenely inexpensive, and it’s already widely commercially available, so this one’s ready to go straight into the clinic,” commented senior investigator Dr. Diona Damian, professor of dermatology at the University of Sydney.

She cautioned that the results apply only to the population studied: adults who had experienced two or more nonmelanoma skin cancers in the past 5 years.

“These are the people we’d be recommending it for – people who have already got a skin cancer track record. It’s not something that we’d recommend at this stage for the general population,” she said. Likewise, the findings do not speak to patients at the other end of the spectrum who are in treatment for advanced or metastatic skin cancer, as they also were excluded.

That said, the researchers are planning additional studies in other populations, such patients who are at high risk because they have immunosuppression, according to Dr. Damian.

“We still need the overall skin cancer prevention strategies of sun-safe behavior, sunscreen, and regular skin surveillance,” she stressed, “but we now have an additional exciting opportunity for affordable skin cancer chemoprevention which we can instantly translate into clinical practice.”

Dr. Peter Paul Yu, ASCO President and a medical oncologist and hematologist who is director of cancer research at the Palo Alto Medical Foundation, Sunnyvale, Calif., commented, “This is a very exciting prevention trial. We all know that we clamor for preventing rather than treating diseases, and this is a major advance for us.”

Exposure to ultraviolet light packs a one-two punch to the skin, both damaging cellular DNA and suppressing the skin’s immune response, according to Dr. Damian. The investigators opted to test nicotinamide as it counters both of these events.

The 386 patients in ONTRAC had heavily sun damaged skin, with a mean of 8 nonmelanoma skin cancers in the past 5 years and 50 keratoses at baseline. They were randomized evenly to receive nicotinamide (500 mg twice daily) or placebo for 12 months.

Results showed that the average number of new nonmelanoma skin cancers per patient during the treatment period was 1.77 in the nicotinamide group and 2.42 in the placebo group. The difference translated to a 23% lower rate of new cancers with the vitamin.

“There were comparable reductions seen for both basal and squamous cell carcinomas,” Dr. Damian noted. “Interestingly, this reduction in skin cancers seemed to start as early as the first 3-month visit. And then when people stopped taking their tablets after 12 months, the benefit was no longer seen. In other words, you need to continue taking the tablets in order for them to be effective.”

The nicotinamide group also had a roughly 15% lower rate of new actinic keratoses, compared with the placebo group.

“Nicotinamide was very well tolerated. There was no difference in adverse events, blood parameters, or blood pressure in the two arms” of the study, reported Dr. Damian. She stressed that it is critically important to distinguish nicotinamide from niacin (nicotinic acid), another form of vitamin B₃ that has a host of side effects such as headache and flushing.

“One of the great things about [nicotinamide] is that it really has hardly any drug interactions, which means that elderly patients who may be taking a whole cocktail of medications for their heart disease and their hypertension, and whatever else, the nicotinamide won’t interact with those,” she added.

Some evidence also has shown nonsteroidal anti-inflammatory drugs to reduce the risk of skin cancer. “The advantage of nicotinamide is that it doesn’t have the potential gastrointestinal bleeding or renal side effects of nonsteroidals, so it may be suitable for a group of people who aren’t suitable for taking nonsteroidals,” she said. “In our ONTRAC study, we didn’t find synergy or additional benefit in people who were coincidentally taking nonsteroidals for other indications.”

The trial’s results should be generalizable to similar high-risk patients in less sunny parts of the world, Dr. Damian said. “If their skin has shown that degree of damage to get skin cancer, then we suspect nicotinamide would offer benefits to them as well.”

Dr. Damian disclosed no relevant conflicts of interest. The study was funded by the National Health & Medical Research Council.