Melanoma

ORLANDO – Patients who express a KIT genetic abnormality represent a small minority of those with melanoma, but there is a lot of interest in the development of specific inhibitors, said Dr. Richard D. Carvajal at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery.

Studies from Dr. Carvajal and other researchers indicate that inhibitors could significantly prolong median progression-free survival for patients who have amplification, overexpression, or a mutation of this genetic driver of melanoma.

In his phase II study of Novartis’ imatinib (Gleevec) for patients with melanoma and KIT alterations, 4 of 25 evaluable patients responded, for an overall durable response rate of 16%. Median progression-free survival was "pretty modest at 3 to 3.5 months," Dr. Carvajal said. Two patients had a complete response to therapy, and another two achieved a partial response (JAMA 2011;305:2327-34).

"So the question is: Can we better select patients likely to respond?" Dr. Carvajal asked at the meeting. "Certainly this is not vemurafenib [Zelboraf], where we get a response in 50% of patients. It could be due to variability in KIT mutations," said Dr. Carvajal, a medical oncologist specializing in melanoma and sarcomas at Memorial Sloan-Kettering Cancer Center in New York.

Only 3% of patients with melanoma harbor a KIT mutation. "You have to have a mutation in KIT; otherwise, the patient is not going to respond to imatinib," he said. The study was preceded by three negative clinical trials in unselected patients (before the mutation was identified).

In another phase II study enrolling only patients with KIT alterations, investigators reported that 10 of 43 patients responded to treatment with imatinib, for a 23% overall response rate (J. Clin. Oncol. 2011;29:2904-9).

Studies are underway with potential KIT inhibitors other than imatinib, including Pfizer’s sunitinib (Sutent), Novartis’ nilotinib (Tasigna), and Bristol-Myers Squibb’s dasatinib (Sprycel).

Sunitinib

Sunitinib is "reasonably promising" for melanoma patients with KIT mutations, said Dr. David Minor, of the California Pacific Center for Melanoma Research and Treatment at the University of California, San Francisco.

He and his colleagues conducted gene sequencing of tumors from 90 patients with advanced melanoma. The findings revealed that 11% featured a KIT mutation (Clin. Cancer Res. 2012:18:1457-63).

Ten of 12 patients treated with sunitinib were evaluable – 4 with KIT mutations and 6 with KIT amplification or overexpression. Although the mutation was a significant predictor of shortened survival time, treatment with sunitinib was associated with complete remission in 1 patient for 15 months and 2 partial responses for 1 and 7 months, he noted. A KIT mutation might be more clinically relevant because there were no complete responses and only one partial response in patients with KIT amplification or overexpression. Dr. Minor is director of inpatient oncology at the California Pacific Medical Center.

Nilotinib

Because only a small percentage of melanoma patients harbor a KIT mutation, conducting large efficacy studies remains a challenge, Dr. Carvajal said. "Indeed, a randomized, phase III trial of nilotinib versus DTIC [dacarbazine] in KIT-mutant melanoma was designed to be the definitive study demonstrating improved outcomes with nilotinib versus DTIC," he said. However, after patient accrual began for the TEAM (Tasigna Efficacy in Advanced Melanoma) trial in 2010, researchers reported difficulty enrolling a sufficient number of patients with metastatic or inoperable melanoma and a KIT mutation. Therefore, they redesigned the study into a single-arm phase II trial of nilotinib alone.

Researchers at the University of Pittsburgh also termed nilotinib a promising agent for melanoma patients with relevant KIT mutations in a review article (Expert Opin. Investig. Drugs 2012;21:861-9).

Dasatinib

Dr. Harriet Kluger and her colleagues at Yale University in New Haven, Conn., reported mixed efficacy for dasatinib in a phase II study (Cancer 2011;117:2202-8).

"At this point I would say that other than in the setting of patients with c-KIT mutations in their tumors, which is still being studied, dasatinib is not a promising agent for this disease," Dr. Kluger said in an interview. She is on the medical oncology faculty at Yale.

She and her colleagues studied 36 evaluable patients with stage 3 or 4 unresectable melanoma. Dasatinib was associated with two partial responses (24 weeks and 64 weeks) and three minor responses. Another patient who initially responded discontinued because of noncompliance. The median progression-free survival was 8 weeks, and the 6-month progression-free survival was 13%. Some activity of dasatinib was observed in a small subset of patients without KIT mutations, suggesting that more research is needed to identify predictive biomarkers for response to this inhibitor.

The KIT gene is located on chromosome 4 and codes for a family of proteins, the receptor tyrosine kinases. KIT function is essential for normal melanocyte genesis and migration. KIT protein signaling also is important for the development of reproductive germ cells, early hematopoietic stem cells, immune mast cells, and interstitial cells of Cajal located in the gastrointestinal tract.

Available data suggest that patients with mutations affecting exons 11 or 13 of KIT may be more likely to achieve clinical benefit with KIT inhibition, Dr. Carvajal said. He added that greater expression of the mutant KIT allele, compared with the wild type, may be a marker of tumors more "addicted" to KIT activation and that may be more susceptible to inhibition.

"This work is still fairly new," he said.

Dr. Carvajal is a consultant to Novartis. Dr. Minor and Dr. Kluger said that they had no relevant disclosures.

ORLANDO – Patients who express a KIT genetic abnormality represent a small minority of those with melanoma, but there is a lot of interest in the development of specific inhibitors, said Dr. Richard D. Carvajal at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery.

Studies from Dr. Carvajal and other researchers indicate that inhibitors could significantly prolong median progression-free survival for patients who have amplification, overexpression, or a mutation of this genetic driver of melanoma.

In his phase II study of Novartis’ imatinib (Gleevec) for patients with melanoma and KIT alterations, 4 of 25 evaluable patients responded, for an overall durable response rate of 16%. Median progression-free survival was "pretty modest at 3 to 3.5 months," Dr. Carvajal said. Two patients had a complete response to therapy, and another two achieved a partial response (JAMA 2011;305:2327-34).

"So the question is: Can we better select patients likely to respond?" Dr. Carvajal asked at the meeting. "Certainly this is not vemurafenib [Zelboraf], where we get a response in 50% of patients. It could be due to variability in KIT mutations," said Dr. Carvajal, a medical oncologist specializing in melanoma and sarcomas at Memorial Sloan-Kettering Cancer Center in New York.

Only 3% of patients with melanoma harbor a KIT mutation. "You have to have a mutation in KIT; otherwise, the patient is not going to respond to imatinib," he said. The study was preceded by three negative clinical trials in unselected patients (before the mutation was identified).

In another phase II study enrolling only patients with KIT alterations, investigators reported that 10 of 43 patients responded to treatment with imatinib, for a 23% overall response rate (J. Clin. Oncol. 2011;29:2904-9).

Studies are underway with potential KIT inhibitors other than imatinib, including Pfizer’s sunitinib (Sutent), Novartis’ nilotinib (Tasigna), and Bristol-Myers Squibb’s dasatinib (Sprycel).

Sunitinib

Sunitinib is "reasonably promising" for melanoma patients with KIT mutations, said Dr. David Minor, of the California Pacific Center for Melanoma Research and Treatment at the University of California, San Francisco.

He and his colleagues conducted gene sequencing of tumors from 90 patients with advanced melanoma. The findings revealed that 11% featured a KIT mutation (Clin. Cancer Res. 2012:18:1457-63).

Ten of 12 patients treated with sunitinib were evaluable – 4 with KIT mutations and 6 with KIT amplification or overexpression. Although the mutation was a significant predictor of shortened survival time, treatment with sunitinib was associated with complete remission in 1 patient for 15 months and 2 partial responses for 1 and 7 months, he noted. A KIT mutation might be more clinically relevant because there were no complete responses and only one partial response in patients with KIT amplification or overexpression. Dr. Minor is director of inpatient oncology at the California Pacific Medical Center.

Nilotinib

Because only a small percentage of melanoma patients harbor a KIT mutation, conducting large efficacy studies remains a challenge, Dr. Carvajal said. "Indeed, a randomized, phase III trial of nilotinib versus DTIC [dacarbazine] in KIT-mutant melanoma was designed to be the definitive study demonstrating improved outcomes with nilotinib versus DTIC," he said. However, after patient accrual began for the TEAM (Tasigna Efficacy in Advanced Melanoma) trial in 2010, researchers reported difficulty enrolling a sufficient number of patients with metastatic or inoperable melanoma and a KIT mutation. Therefore, they redesigned the study into a single-arm phase II trial of nilotinib alone.

Researchers at the University of Pittsburgh also termed nilotinib a promising agent for melanoma patients with relevant KIT mutations in a review article (Expert Opin. Investig. Drugs 2012;21:861-9).

Dasatinib

Dr. Harriet Kluger and her colleagues at Yale University in New Haven, Conn., reported mixed efficacy for dasatinib in a phase II study (Cancer 2011;117:2202-8).

"At this point I would say that other than in the setting of patients with c-KIT mutations in their tumors, which is still being studied, dasatinib is not a promising agent for this disease," Dr. Kluger said in an interview. She is on the medical oncology faculty at Yale.

She and her colleagues studied 36 evaluable patients with stage 3 or 4 unresectable melanoma. Dasatinib was associated with two partial responses (24 weeks and 64 weeks) and three minor responses. Another patient who initially responded discontinued because of noncompliance. The median progression-free survival was 8 weeks, and the 6-month progression-free survival was 13%. Some activity of dasatinib was observed in a small subset of patients without KIT mutations, suggesting that more research is needed to identify predictive biomarkers for response to this inhibitor.

The KIT gene is located on chromosome 4 and codes for a family of proteins, the receptor tyrosine kinases. KIT function is essential for normal melanocyte genesis and migration. KIT protein signaling also is important for the development of reproductive germ cells, early hematopoietic stem cells, immune mast cells, and interstitial cells of Cajal located in the gastrointestinal tract.

Available data suggest that patients with mutations affecting exons 11 or 13 of KIT may be more likely to achieve clinical benefit with KIT inhibition, Dr. Carvajal said. He added that greater expression of the mutant KIT allele, compared with the wild type, may be a marker of tumors more "addicted" to KIT activation and that may be more susceptible to inhibition.

"This work is still fairly new," he said.

Dr. Carvajal is a consultant to Novartis. Dr. Minor and Dr. Kluger said that they had no relevant disclosures.

ORLANDO – Patients who express a KIT genetic abnormality represent a small minority of those with melanoma, but there is a lot of interest in the development of specific inhibitors, said Dr. Richard D. Carvajal at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery.

Studies from Dr. Carvajal and other researchers indicate that inhibitors could significantly prolong median progression-free survival for patients who have amplification, overexpression, or a mutation of this genetic driver of melanoma.

In his phase II study of Novartis’ imatinib (Gleevec) for patients with melanoma and KIT alterations, 4 of 25 evaluable patients responded, for an overall durable response rate of 16%. Median progression-free survival was "pretty modest at 3 to 3.5 months," Dr. Carvajal said. Two patients had a complete response to therapy, and another two achieved a partial response (JAMA 2011;305:2327-34).

"So the question is: Can we better select patients likely to respond?" Dr. Carvajal asked at the meeting. "Certainly this is not vemurafenib [Zelboraf], where we get a response in 50% of patients. It could be due to variability in KIT mutations," said Dr. Carvajal, a medical oncologist specializing in melanoma and sarcomas at Memorial Sloan-Kettering Cancer Center in New York.

Only 3% of patients with melanoma harbor a KIT mutation. "You have to have a mutation in KIT; otherwise, the patient is not going to respond to imatinib," he said. The study was preceded by three negative clinical trials in unselected patients (before the mutation was identified).

In another phase II study enrolling only patients with KIT alterations, investigators reported that 10 of 43 patients responded to treatment with imatinib, for a 23% overall response rate (J. Clin. Oncol. 2011;29:2904-9).

Studies are underway with potential KIT inhibitors other than imatinib, including Pfizer’s sunitinib (Sutent), Novartis’ nilotinib (Tasigna), and Bristol-Myers Squibb’s dasatinib (Sprycel).

Sunitinib

Sunitinib is "reasonably promising" for melanoma patients with KIT mutations, said Dr. David Minor, of the California Pacific Center for Melanoma Research and Treatment at the University of California, San Francisco.

He and his colleagues conducted gene sequencing of tumors from 90 patients with advanced melanoma. The findings revealed that 11% featured a KIT mutation (Clin. Cancer Res. 2012:18:1457-63).

Ten of 12 patients treated with sunitinib were evaluable – 4 with KIT mutations and 6 with KIT amplification or overexpression. Although the mutation was a significant predictor of shortened survival time, treatment with sunitinib was associated with complete remission in 1 patient for 15 months and 2 partial responses for 1 and 7 months, he noted. A KIT mutation might be more clinically relevant because there were no complete responses and only one partial response in patients with KIT amplification or overexpression. Dr. Minor is director of inpatient oncology at the California Pacific Medical Center.

Nilotinib

Because only a small percentage of melanoma patients harbor a KIT mutation, conducting large efficacy studies remains a challenge, Dr. Carvajal said. "Indeed, a randomized, phase III trial of nilotinib versus DTIC [dacarbazine] in KIT-mutant melanoma was designed to be the definitive study demonstrating improved outcomes with nilotinib versus DTIC," he said. However, after patient accrual began for the TEAM (Tasigna Efficacy in Advanced Melanoma) trial in 2010, researchers reported difficulty enrolling a sufficient number of patients with metastatic or inoperable melanoma and a KIT mutation. Therefore, they redesigned the study into a single-arm phase II trial of nilotinib alone.

Researchers at the University of Pittsburgh also termed nilotinib a promising agent for melanoma patients with relevant KIT mutations in a review article (Expert Opin. Investig. Drugs 2012;21:861-9).

Dasatinib

Dr. Harriet Kluger and her colleagues at Yale University in New Haven, Conn., reported mixed efficacy for dasatinib in a phase II study (Cancer 2011;117:2202-8).

"At this point I would say that other than in the setting of patients with c-KIT mutations in their tumors, which is still being studied, dasatinib is not a promising agent for this disease," Dr. Kluger said in an interview. She is on the medical oncology faculty at Yale.

She and her colleagues studied 36 evaluable patients with stage 3 or 4 unresectable melanoma. Dasatinib was associated with two partial responses (24 weeks and 64 weeks) and three minor responses. Another patient who initially responded discontinued because of noncompliance. The median progression-free survival was 8 weeks, and the 6-month progression-free survival was 13%. Some activity of dasatinib was observed in a small subset of patients without KIT mutations, suggesting that more research is needed to identify predictive biomarkers for response to this inhibitor.

The KIT gene is located on chromosome 4 and codes for a family of proteins, the receptor tyrosine kinases. KIT function is essential for normal melanocyte genesis and migration. KIT protein signaling also is important for the development of reproductive germ cells, early hematopoietic stem cells, immune mast cells, and interstitial cells of Cajal located in the gastrointestinal tract.

Available data suggest that patients with mutations affecting exons 11 or 13 of KIT may be more likely to achieve clinical benefit with KIT inhibition, Dr. Carvajal said. He added that greater expression of the mutant KIT allele, compared with the wild type, may be a marker of tumors more "addicted" to KIT activation and that may be more susceptible to inhibition.

"This work is still fairly new," he said.

Dr. Carvajal is a consultant to Novartis. Dr. Minor and Dr. Kluger said that they had no relevant disclosures.

Riddle me this: How is a fish like a canary?

As you know, miners used canaries underground, where they functioned as warning systems – when toxic gases leaked into the shaft, the birds would die, signaling a need for the minors to leave the shaft.

Today, it seems prudent to heed the plight of the Great Barrier Reef coral trout, Plectropomus leopardus.

Courtesy Newcastle University/Australian Institute of Marine Science

According to Dr. Michael Sweet, a marine research associate at Newcastle (Australia) University, 15% of coral trout caught in two reef locations in Australia were found to have skin cancer. This is the first report of melanoma occurring in a wild fish population, he noted.

Coral trout are a valuable food and sport fish that live at a depth of up to 30 m in unpolluted, clear water – well within the 60-m reach of Australia’s strong UVB radiation, wrote Dr. Sweet.

Several decades ago, there was no problem. But today, a hovering ozone hole seems to have compromised the fish’s health, he noted.

After he heard of coral trout with dark skin lesions, Dr. Sweet went reef fishing. He and his colleagues pulled in 136; 20 of the fish showed visible skin lesions that were raised and darkly pigmented. He took samples from each fish and tested them for microbial, fungal, and parasitic infections (PLoS ONE 2012 Aug. 1 [doi: 10.1371/journal.pone.0041989])

The fish had no infections or disease. But, histologically, they showed disorganized pleomorphic cells, melanocytes, epithelioid-like cells, melanophores, and macromelanophore cells, consistent with lesions induced in a fish cancer model.

The fishes’ behavior seemed unaffected, and all the lesions appeared to be stage I or II. But that isn’t necessarily reassuring, Dr. Sweet reported. Fish exhibiting stage III, IV, or V cancers may show behavioral differences in the wild and may, therefore, have not been caught.

So – other than a general concern for the health of the Great Barrier Reef – why should we care about wild fish developing melanoma?

Jen Makin, a research and evaluation manager for Australia’s SunSmart program, cited unsettling figures about the Australian UV situation and skin cancer (Health Promot. J. Austr. 2011;22:S39-41).

"It is estimated that nearly 450,000 Australians get skin cancer every year," she wrote – 95% of the cancers are directly related to UV radiation.

The ozone layer is slowly recovering its health, but an ever-hotter Earth may undo that skin-protecting change. "Before recovery, it is expected that higher levels of UV radiation will continue in most Australian regions, with an associated higher risk of skin cancer. Indeed, recent data show increases in surface UV radiation throughout Australia since the 1970s. Second, mean temperatures in Australia have increased over the past 30 years and are projected to rise further by 2030," she wrote.

In hot weather, adults spend more time outdoors, are less likely to cover up, and are more likely to get burned. And – as the coral trout have proved – there seem to be few places to hide.

–Michele Sullivan (on Twitter @Alz_Gal)

Riddle me this: How is a fish like a canary?

As you know, miners used canaries underground, where they functioned as warning systems – when toxic gases leaked into the shaft, the birds would die, signaling a need for the minors to leave the shaft.

Today, it seems prudent to heed the plight of the Great Barrier Reef coral trout, Plectropomus leopardus.

Courtesy Newcastle University/Australian Institute of Marine Science

According to Dr. Michael Sweet, a marine research associate at Newcastle (Australia) University, 15% of coral trout caught in two reef locations in Australia were found to have skin cancer. This is the first report of melanoma occurring in a wild fish population, he noted.

Coral trout are a valuable food and sport fish that live at a depth of up to 30 m in unpolluted, clear water – well within the 60-m reach of Australia’s strong UVB radiation, wrote Dr. Sweet.

Several decades ago, there was no problem. But today, a hovering ozone hole seems to have compromised the fish’s health, he noted.

After he heard of coral trout with dark skin lesions, Dr. Sweet went reef fishing. He and his colleagues pulled in 136; 20 of the fish showed visible skin lesions that were raised and darkly pigmented. He took samples from each fish and tested them for microbial, fungal, and parasitic infections (PLoS ONE 2012 Aug. 1 [doi: 10.1371/journal.pone.0041989])

The fish had no infections or disease. But, histologically, they showed disorganized pleomorphic cells, melanocytes, epithelioid-like cells, melanophores, and macromelanophore cells, consistent with lesions induced in a fish cancer model.

The fishes’ behavior seemed unaffected, and all the lesions appeared to be stage I or II. But that isn’t necessarily reassuring, Dr. Sweet reported. Fish exhibiting stage III, IV, or V cancers may show behavioral differences in the wild and may, therefore, have not been caught.

So – other than a general concern for the health of the Great Barrier Reef – why should we care about wild fish developing melanoma?

Jen Makin, a research and evaluation manager for Australia’s SunSmart program, cited unsettling figures about the Australian UV situation and skin cancer (Health Promot. J. Austr. 2011;22:S39-41).

"It is estimated that nearly 450,000 Australians get skin cancer every year," she wrote – 95% of the cancers are directly related to UV radiation.

The ozone layer is slowly recovering its health, but an ever-hotter Earth may undo that skin-protecting change. "Before recovery, it is expected that higher levels of UV radiation will continue in most Australian regions, with an associated higher risk of skin cancer. Indeed, recent data show increases in surface UV radiation throughout Australia since the 1970s. Second, mean temperatures in Australia have increased over the past 30 years and are projected to rise further by 2030," she wrote.

In hot weather, adults spend more time outdoors, are less likely to cover up, and are more likely to get burned. And – as the coral trout have proved – there seem to be few places to hide.

–Michele Sullivan (on Twitter @Alz_Gal)

Riddle me this: How is a fish like a canary?

As you know, miners used canaries underground, where they functioned as warning systems – when toxic gases leaked into the shaft, the birds would die, signaling a need for the minors to leave the shaft.

Today, it seems prudent to heed the plight of the Great Barrier Reef coral trout, Plectropomus leopardus.

Courtesy Newcastle University/Australian Institute of Marine Science

According to Dr. Michael Sweet, a marine research associate at Newcastle (Australia) University, 15% of coral trout caught in two reef locations in Australia were found to have skin cancer. This is the first report of melanoma occurring in a wild fish population, he noted.

Coral trout are a valuable food and sport fish that live at a depth of up to 30 m in unpolluted, clear water – well within the 60-m reach of Australia’s strong UVB radiation, wrote Dr. Sweet.

Several decades ago, there was no problem. But today, a hovering ozone hole seems to have compromised the fish’s health, he noted.

After he heard of coral trout with dark skin lesions, Dr. Sweet went reef fishing. He and his colleagues pulled in 136; 20 of the fish showed visible skin lesions that were raised and darkly pigmented. He took samples from each fish and tested them for microbial, fungal, and parasitic infections (PLoS ONE 2012 Aug. 1 [doi: 10.1371/journal.pone.0041989])

The fish had no infections or disease. But, histologically, they showed disorganized pleomorphic cells, melanocytes, epithelioid-like cells, melanophores, and macromelanophore cells, consistent with lesions induced in a fish cancer model.

The fishes’ behavior seemed unaffected, and all the lesions appeared to be stage I or II. But that isn’t necessarily reassuring, Dr. Sweet reported. Fish exhibiting stage III, IV, or V cancers may show behavioral differences in the wild and may, therefore, have not been caught.

So – other than a general concern for the health of the Great Barrier Reef – why should we care about wild fish developing melanoma?

Jen Makin, a research and evaluation manager for Australia’s SunSmart program, cited unsettling figures about the Australian UV situation and skin cancer (Health Promot. J. Austr. 2011;22:S39-41).

"It is estimated that nearly 450,000 Australians get skin cancer every year," she wrote – 95% of the cancers are directly related to UV radiation.

The ozone layer is slowly recovering its health, but an ever-hotter Earth may undo that skin-protecting change. "Before recovery, it is expected that higher levels of UV radiation will continue in most Australian regions, with an associated higher risk of skin cancer. Indeed, recent data show increases in surface UV radiation throughout Australia since the 1970s. Second, mean temperatures in Australia have increased over the past 30 years and are projected to rise further by 2030," she wrote.

In hot weather, adults spend more time outdoors, are less likely to cover up, and are more likely to get burned. And – as the coral trout have proved – there seem to be few places to hide.

–Michele Sullivan (on Twitter @Alz_Gal)

MINNEAPOLIS – Pregnancy-associated cancers are increasing, although the phenomenon of delayed childbirth is only partially responsible, researchers suggest.

From 1994 to 2008, the crude incidence of pregnancy-associated cancer increased from 112 to 192 per 100,000 pregnancies (P less than .001) in an analysis of 787,907 Australian women.

During the same period, the number of Australian mothers aged 35 years or more nearly doubled from 13% to 24%, including an increase from 2% to 4% of mothers over age 40, Christine L. Roberts, Ph.D., said at the annual meeting of the Society for Pediatric and Perinatal Epidemiologic Research.

Patrice Wendling/IMNG Medical Media

After the cancer rate was standardized to the age of the 1994 population, however, only 14% of the increase in cancer was explained by increasing maternal age, said Dr. Roberts of the University of Sydney, New South Wales, Australia.

"Improved diagnostic techniques, detection, and interracial health services likely contribute to the unexplained portion," she said. "The increasing incidence of cancer confirmed a clinical impression that obstetricians were seeing women with cancer more frequently, although of course it remains uncommon."

The growing number of women postponing childbearing has raised concerns that the incidence of pregnancy-associated cancer would rise. The incidence is generally reported to be about 1 in 1,000 pregnancies, but estimates based largely on cancer reports have been imprecise, Dr. Roberts said.

The investigators obtained cancer and maternal information from linked cancer registry, birth, and hospital records for 1.31 million pregnancies and 1.33 million infants among 781,907 women in Australia.

During the study period, 1,798 women had a new cancer diagnosis: 499 during pregnancy and 1,299 within 12 months of delivery. This equates to 137.3 cancers per 100,000 pregnancies, Dr. Roberts said.

There were 42 cancer deaths, or 3.2 deaths per 100,000 pregnancies.

The highest proportion of cancers (14.5%) was diagnosed in the first 2 months post partum, lending support to the rationale that women and physicians may incorrectly attribute cancer-related symptoms to the physiologic changes of pregnancy and may be reluctant to use radiographs or invasive procedures during pregnancy, she observed.

The cancers were predominantly melanoma (599) or breast cancer (377), followed by thyroid/endocrine (228) and lymphohematopoietic (151) cancers.

Melanoma was twice as likely to be observed in pregnant women as in women of similar reproductive age (observed to expected ratio, 2.2), according to the authors, led by Dr. Yuen Yi (Cathy) Lee of the New South Wales Ministry of Health in North Sydney, Australia.

In prior studies, breast and thyroid cancer were the most common pregnancy-related cancers in California in the 1990s (Am. J. Obstet. Gynecol. 2003;189:1128-35), whereas more recently, melanoma and cervical cancer were the most common cancers during pregnancy in Norway (J. Clin. Oncol. 2009;27:45-51), Dr. Roberts noted.

In logistic regression analysis adjusted for age, country of birth, socioeconomic status, rural residence, parity, plurality, previous cancer, and assisted reproductive technology, significant risk factors for a pregnancy-associated cancer were previous cancer diagnosis (adjusted odds ratio, 3.8), multiple pregnancy (OR, 1.5), age 30-34 years (OR, 2.1), age 35-39 years (OR, 3.0), and age 40 years or older (OR, 3.6).

Women with a cancer diagnosis had a significantly higher risk of thromboembolic events (OR, 10.2), sepsis (OR, 4.3), and life-threatening maternal morbidity (OR, 6.9) after adjustment for maternal age, socioeconomic status, plurality, parity, previous preterm birth, diabetes, and hypertension.

A novel finding was that cancer during pregnancy also was associated with large-for-gestational age infants (OR, 1.5), said Dr. Roberts, who pointed out that large-for-gestational age is also a risk factor for pediatric cancer.

"Elevated levels of maternal hormone angiogenic factors during pregnancy may influence both infant size and tumor growth," she speculated.

Dr. Roberts said there is an Australian national policy on cervical screening recommending that Pap smears be offered to every woman presenting for antenatal care who has not had cervical screening within the past 2 years; however, this was introduced in 2008 at the end of the study period. "We are not aware of other policies for screening during pregnancy," she added.

Full details of the study are expected to be published in the coming weeks (BJOG 2012 [doi: 10.111/j.1471-0528.2012.03475.x]).

The authors report no conflicts of interest.

MINNEAPOLIS – Pregnancy-associated cancers are increasing, although the phenomenon of delayed childbirth is only partially responsible, researchers suggest.

From 1994 to 2008, the crude incidence of pregnancy-associated cancer increased from 112 to 192 per 100,000 pregnancies (P less than .001) in an analysis of 787,907 Australian women.

During the same period, the number of Australian mothers aged 35 years or more nearly doubled from 13% to 24%, including an increase from 2% to 4% of mothers over age 40, Christine L. Roberts, Ph.D., said at the annual meeting of the Society for Pediatric and Perinatal Epidemiologic Research.

Patrice Wendling/IMNG Medical Media

After the cancer rate was standardized to the age of the 1994 population, however, only 14% of the increase in cancer was explained by increasing maternal age, said Dr. Roberts of the University of Sydney, New South Wales, Australia.

"Improved diagnostic techniques, detection, and interracial health services likely contribute to the unexplained portion," she said. "The increasing incidence of cancer confirmed a clinical impression that obstetricians were seeing women with cancer more frequently, although of course it remains uncommon."

The growing number of women postponing childbearing has raised concerns that the incidence of pregnancy-associated cancer would rise. The incidence is generally reported to be about 1 in 1,000 pregnancies, but estimates based largely on cancer reports have been imprecise, Dr. Roberts said.

The investigators obtained cancer and maternal information from linked cancer registry, birth, and hospital records for 1.31 million pregnancies and 1.33 million infants among 781,907 women in Australia.

During the study period, 1,798 women had a new cancer diagnosis: 499 during pregnancy and 1,299 within 12 months of delivery. This equates to 137.3 cancers per 100,000 pregnancies, Dr. Roberts said.

There were 42 cancer deaths, or 3.2 deaths per 100,000 pregnancies.

The highest proportion of cancers (14.5%) was diagnosed in the first 2 months post partum, lending support to the rationale that women and physicians may incorrectly attribute cancer-related symptoms to the physiologic changes of pregnancy and may be reluctant to use radiographs or invasive procedures during pregnancy, she observed.

The cancers were predominantly melanoma (599) or breast cancer (377), followed by thyroid/endocrine (228) and lymphohematopoietic (151) cancers.

Melanoma was twice as likely to be observed in pregnant women as in women of similar reproductive age (observed to expected ratio, 2.2), according to the authors, led by Dr. Yuen Yi (Cathy) Lee of the New South Wales Ministry of Health in North Sydney, Australia.

In prior studies, breast and thyroid cancer were the most common pregnancy-related cancers in California in the 1990s (Am. J. Obstet. Gynecol. 2003;189:1128-35), whereas more recently, melanoma and cervical cancer were the most common cancers during pregnancy in Norway (J. Clin. Oncol. 2009;27:45-51), Dr. Roberts noted.

In logistic regression analysis adjusted for age, country of birth, socioeconomic status, rural residence, parity, plurality, previous cancer, and assisted reproductive technology, significant risk factors for a pregnancy-associated cancer were previous cancer diagnosis (adjusted odds ratio, 3.8), multiple pregnancy (OR, 1.5), age 30-34 years (OR, 2.1), age 35-39 years (OR, 3.0), and age 40 years or older (OR, 3.6).

Women with a cancer diagnosis had a significantly higher risk of thromboembolic events (OR, 10.2), sepsis (OR, 4.3), and life-threatening maternal morbidity (OR, 6.9) after adjustment for maternal age, socioeconomic status, plurality, parity, previous preterm birth, diabetes, and hypertension.

A novel finding was that cancer during pregnancy also was associated with large-for-gestational age infants (OR, 1.5), said Dr. Roberts, who pointed out that large-for-gestational age is also a risk factor for pediatric cancer.

"Elevated levels of maternal hormone angiogenic factors during pregnancy may influence both infant size and tumor growth," she speculated.

Dr. Roberts said there is an Australian national policy on cervical screening recommending that Pap smears be offered to every woman presenting for antenatal care who has not had cervical screening within the past 2 years; however, this was introduced in 2008 at the end of the study period. "We are not aware of other policies for screening during pregnancy," she added.

Full details of the study are expected to be published in the coming weeks (BJOG 2012 [doi: 10.111/j.1471-0528.2012.03475.x]).

The authors report no conflicts of interest.

MINNEAPOLIS – Pregnancy-associated cancers are increasing, although the phenomenon of delayed childbirth is only partially responsible, researchers suggest.

From 1994 to 2008, the crude incidence of pregnancy-associated cancer increased from 112 to 192 per 100,000 pregnancies (P less than .001) in an analysis of 787,907 Australian women.

During the same period, the number of Australian mothers aged 35 years or more nearly doubled from 13% to 24%, including an increase from 2% to 4% of mothers over age 40, Christine L. Roberts, Ph.D., said at the annual meeting of the Society for Pediatric and Perinatal Epidemiologic Research.

Patrice Wendling/IMNG Medical Media

After the cancer rate was standardized to the age of the 1994 population, however, only 14% of the increase in cancer was explained by increasing maternal age, said Dr. Roberts of the University of Sydney, New South Wales, Australia.

"Improved diagnostic techniques, detection, and interracial health services likely contribute to the unexplained portion," she said. "The increasing incidence of cancer confirmed a clinical impression that obstetricians were seeing women with cancer more frequently, although of course it remains uncommon."

The growing number of women postponing childbearing has raised concerns that the incidence of pregnancy-associated cancer would rise. The incidence is generally reported to be about 1 in 1,000 pregnancies, but estimates based largely on cancer reports have been imprecise, Dr. Roberts said.

The investigators obtained cancer and maternal information from linked cancer registry, birth, and hospital records for 1.31 million pregnancies and 1.33 million infants among 781,907 women in Australia.

During the study period, 1,798 women had a new cancer diagnosis: 499 during pregnancy and 1,299 within 12 months of delivery. This equates to 137.3 cancers per 100,000 pregnancies, Dr. Roberts said.

There were 42 cancer deaths, or 3.2 deaths per 100,000 pregnancies.

The highest proportion of cancers (14.5%) was diagnosed in the first 2 months post partum, lending support to the rationale that women and physicians may incorrectly attribute cancer-related symptoms to the physiologic changes of pregnancy and may be reluctant to use radiographs or invasive procedures during pregnancy, she observed.

The cancers were predominantly melanoma (599) or breast cancer (377), followed by thyroid/endocrine (228) and lymphohematopoietic (151) cancers.

Melanoma was twice as likely to be observed in pregnant women as in women of similar reproductive age (observed to expected ratio, 2.2), according to the authors, led by Dr. Yuen Yi (Cathy) Lee of the New South Wales Ministry of Health in North Sydney, Australia.

In prior studies, breast and thyroid cancer were the most common pregnancy-related cancers in California in the 1990s (Am. J. Obstet. Gynecol. 2003;189:1128-35), whereas more recently, melanoma and cervical cancer were the most common cancers during pregnancy in Norway (J. Clin. Oncol. 2009;27:45-51), Dr. Roberts noted.

In logistic regression analysis adjusted for age, country of birth, socioeconomic status, rural residence, parity, plurality, previous cancer, and assisted reproductive technology, significant risk factors for a pregnancy-associated cancer were previous cancer diagnosis (adjusted odds ratio, 3.8), multiple pregnancy (OR, 1.5), age 30-34 years (OR, 2.1), age 35-39 years (OR, 3.0), and age 40 years or older (OR, 3.6).

Women with a cancer diagnosis had a significantly higher risk of thromboembolic events (OR, 10.2), sepsis (OR, 4.3), and life-threatening maternal morbidity (OR, 6.9) after adjustment for maternal age, socioeconomic status, plurality, parity, previous preterm birth, diabetes, and hypertension.

A novel finding was that cancer during pregnancy also was associated with large-for-gestational age infants (OR, 1.5), said Dr. Roberts, who pointed out that large-for-gestational age is also a risk factor for pediatric cancer.

"Elevated levels of maternal hormone angiogenic factors during pregnancy may influence both infant size and tumor growth," she speculated.

Dr. Roberts said there is an Australian national policy on cervical screening recommending that Pap smears be offered to every woman presenting for antenatal care who has not had cervical screening within the past 2 years; however, this was introduced in 2008 at the end of the study period. "We are not aware of other policies for screening during pregnancy," she added.

Full details of the study are expected to be published in the coming weeks (BJOG 2012 [doi: 10.111/j.1471-0528.2012.03475.x]).

The authors report no conflicts of interest.

In this month's program, Dr. Jeffrey Curtis discusses his study, which found new evidence supporting the safety of the shingles vaccine for patients on biologics.

Then, Dr. Jonathan Silverberg talks about the best climates for children with eczema.

Dr. Bruce Brod of the American Academy of Dermatology reports on which states have the toughest laws on indoor tanning, and he highlights the latest legislation on the matter.

Meanwhile, Dr. Lily Talakoub talks about a common summer skin condition, Pityrosporum folliculitis, and Dr. Alan Rockoff presents his musical marketing plan.

Don't miss another episode of The Skinny Podcast; subscribe for free on iTunes!

In this month's program, Dr. Jeffrey Curtis discusses his study, which found new evidence supporting the safety of the shingles vaccine for patients on biologics.

Then, Dr. Jonathan Silverberg talks about the best climates for children with eczema.

Dr. Bruce Brod of the American Academy of Dermatology reports on which states have the toughest laws on indoor tanning, and he highlights the latest legislation on the matter.

Meanwhile, Dr. Lily Talakoub talks about a common summer skin condition, Pityrosporum folliculitis, and Dr. Alan Rockoff presents his musical marketing plan.

Don't miss another episode of The Skinny Podcast; subscribe for free on iTunes!

In this month's program, Dr. Jeffrey Curtis discusses his study, which found new evidence supporting the safety of the shingles vaccine for patients on biologics.

Then, Dr. Jonathan Silverberg talks about the best climates for children with eczema.

Dr. Bruce Brod of the American Academy of Dermatology reports on which states have the toughest laws on indoor tanning, and he highlights the latest legislation on the matter.

Meanwhile, Dr. Lily Talakoub talks about a common summer skin condition, Pityrosporum folliculitis, and Dr. Alan Rockoff presents his musical marketing plan.

Don't miss another episode of The Skinny Podcast; subscribe for free on iTunes!

Commonly used photosensitizing antihypertensive drugs increase the risk for lip cancer by two- to fourfold, according to a study published online Aug. 6 in Archives of Internal Medicine.

"Lip cancer is rare, and an increased risk of its development is generally outweighed by the benefits of drugs that are effective for other conditions. However, physicians prescribing photosensitizing drugs should ascertain whether patients are at high risk of lip cancer because of their fair skin and long-term sun exposure, and discuss lip protection with them," wrote Dr. Gary D. Friedman of the division of research, Kaiser Permanente Medical Care Program, Oakland Calif., and his colleagues. "Likely preventive measures are simple: a hat with a sufficiently wide brim to shade the lips, and lip sunscreens," they added.

The diuretics hydrochlorothiazide and hydrochlorothiazide-triamterene, as well as the calcium channel blocker nifedipine, were associated with at least a doubling in the risk for lip cancer in a study involving 23,616 hypertensive non-Hispanic white adults. The association between lip cancer and the ACE inhibitor lisinopril, which also is photosensitizing, was characterized as "equivocal." And atenolol, a beta-adrenergic blocker that is not photosensitizing, was not linked to a higher risk.

Dr. Friedman and his colleagues used prescription data from the Kaiser Permanente pharmacy database and information from its cancer registry to perform a case-control study examining the relationship between the four classes of antihypertensive medications and lip cancer. They assessed the period from 1994 through 2008. The database includes an ethnically and socioeconomically diverse population of residents in the San Francisco and central valley regions of California.

There were few cases of lip cancer among nonwhite patients, so the analysis was restricted to white patients. Those with human immunodeficiency virus infection and those taking immunosuppressants after receiving organ transplants also were excluded because these factors were likely to be confounders.

The study population comprised 712 patients with lip cancer and 22,904 age-matched control patients. Nearly all malignancies were squamous cell. As expected, cigarette smokers in both study groups were more likely than nonsmokers to develop lip cancer.

The risk of developing lip cancer showed a dose-response relationship with the use of certain antihypertensive drugs, with the risk increasing as the duration of drug use increased. For patients treated with hydrochlorothiazide for 5 years or more, the odds ratio of developing lip cancer was 4.22. The OR for the combination drug hydrochlorothiazide-triamterene was 2.82, and the OR for nifedipine was 2.50. The OR was of borderline significance for lisinopril (1.42).

In contrast, for patients treated with atenolol for 5 years or more, the risk of developing lip cancer was reduced, with an odds ratio of 0.54, the investigators reported (Arch. Intern. Med. 2012 Aug. 6 [doi:10.1001/archinternmed.2012.2754]).

It should not be surprising that previous large clinical trials of these drugs’ efficacy failed to find an association with lip cancer, because of the rarity of the malignancy, they added.

For example, one study of antihypertensive medications involved more than 33,000 patients followed for a mean of 5 years. And after the investigators excluded the nonwhite patients, adjusted for the much lower incidence of lip cancer in women (who comprised half of the study population) than in men, and considered the low background incidence of the malignancy, they found that only seven lip cancers would have been expected to be detected in all the treatment groups combined, reported Dr. Friedman, also of the department of health research and policy, Stanford (Calif.) University, and his associates.

"Although the relatively high odds ratios, the evidence for specificity, and the biological mechanism are consistent with a causal relationship, causality cannot usually be established by a single observational study such as ours. Further investigations are needed to confirm and characterize relationships between photosensitizing antihypertensive agents and lip cancer," the researchers noted.

The study was limited because the researchers were unable to account for patients’ sun exposure, which is the most important factor contributing to lip cancer risk. "However, it does not seem likely that users of the antihypertensive drugs associated with lip cancer experience a great deal more sun exposure than nonusers or than users of atenolol," they wrote.

This study was supported by the National Cancer Institute. Dr. Friedman reported ties to Allergan, and his associates reported ties to Genentech, Merck, Sanofi-Aventis, and Takeda.

Commonly used photosensitizing antihypertensive drugs increase the risk for lip cancer by two- to fourfold, according to a study published online Aug. 6 in Archives of Internal Medicine.

"Lip cancer is rare, and an increased risk of its development is generally outweighed by the benefits of drugs that are effective for other conditions. However, physicians prescribing photosensitizing drugs should ascertain whether patients are at high risk of lip cancer because of their fair skin and long-term sun exposure, and discuss lip protection with them," wrote Dr. Gary D. Friedman of the division of research, Kaiser Permanente Medical Care Program, Oakland Calif., and his colleagues. "Likely preventive measures are simple: a hat with a sufficiently wide brim to shade the lips, and lip sunscreens," they added.

The diuretics hydrochlorothiazide and hydrochlorothiazide-triamterene, as well as the calcium channel blocker nifedipine, were associated with at least a doubling in the risk for lip cancer in a study involving 23,616 hypertensive non-Hispanic white adults. The association between lip cancer and the ACE inhibitor lisinopril, which also is photosensitizing, was characterized as "equivocal." And atenolol, a beta-adrenergic blocker that is not photosensitizing, was not linked to a higher risk.

Dr. Friedman and his colleagues used prescription data from the Kaiser Permanente pharmacy database and information from its cancer registry to perform a case-control study examining the relationship between the four classes of antihypertensive medications and lip cancer. They assessed the period from 1994 through 2008. The database includes an ethnically and socioeconomically diverse population of residents in the San Francisco and central valley regions of California.

There were few cases of lip cancer among nonwhite patients, so the analysis was restricted to white patients. Those with human immunodeficiency virus infection and those taking immunosuppressants after receiving organ transplants also were excluded because these factors were likely to be confounders.

The study population comprised 712 patients with lip cancer and 22,904 age-matched control patients. Nearly all malignancies were squamous cell. As expected, cigarette smokers in both study groups were more likely than nonsmokers to develop lip cancer.

The risk of developing lip cancer showed a dose-response relationship with the use of certain antihypertensive drugs, with the risk increasing as the duration of drug use increased. For patients treated with hydrochlorothiazide for 5 years or more, the odds ratio of developing lip cancer was 4.22. The OR for the combination drug hydrochlorothiazide-triamterene was 2.82, and the OR for nifedipine was 2.50. The OR was of borderline significance for lisinopril (1.42).

In contrast, for patients treated with atenolol for 5 years or more, the risk of developing lip cancer was reduced, with an odds ratio of 0.54, the investigators reported (Arch. Intern. Med. 2012 Aug. 6 [doi:10.1001/archinternmed.2012.2754]).

It should not be surprising that previous large clinical trials of these drugs’ efficacy failed to find an association with lip cancer, because of the rarity of the malignancy, they added.

For example, one study of antihypertensive medications involved more than 33,000 patients followed for a mean of 5 years. And after the investigators excluded the nonwhite patients, adjusted for the much lower incidence of lip cancer in women (who comprised half of the study population) than in men, and considered the low background incidence of the malignancy, they found that only seven lip cancers would have been expected to be detected in all the treatment groups combined, reported Dr. Friedman, also of the department of health research and policy, Stanford (Calif.) University, and his associates.

"Although the relatively high odds ratios, the evidence for specificity, and the biological mechanism are consistent with a causal relationship, causality cannot usually be established by a single observational study such as ours. Further investigations are needed to confirm and characterize relationships between photosensitizing antihypertensive agents and lip cancer," the researchers noted.

The study was limited because the researchers were unable to account for patients’ sun exposure, which is the most important factor contributing to lip cancer risk. "However, it does not seem likely that users of the antihypertensive drugs associated with lip cancer experience a great deal more sun exposure than nonusers or than users of atenolol," they wrote.

This study was supported by the National Cancer Institute. Dr. Friedman reported ties to Allergan, and his associates reported ties to Genentech, Merck, Sanofi-Aventis, and Takeda.

Commonly used photosensitizing antihypertensive drugs increase the risk for lip cancer by two- to fourfold, according to a study published online Aug. 6 in Archives of Internal Medicine.

"Lip cancer is rare, and an increased risk of its development is generally outweighed by the benefits of drugs that are effective for other conditions. However, physicians prescribing photosensitizing drugs should ascertain whether patients are at high risk of lip cancer because of their fair skin and long-term sun exposure, and discuss lip protection with them," wrote Dr. Gary D. Friedman of the division of research, Kaiser Permanente Medical Care Program, Oakland Calif., and his colleagues. "Likely preventive measures are simple: a hat with a sufficiently wide brim to shade the lips, and lip sunscreens," they added.

The diuretics hydrochlorothiazide and hydrochlorothiazide-triamterene, as well as the calcium channel blocker nifedipine, were associated with at least a doubling in the risk for lip cancer in a study involving 23,616 hypertensive non-Hispanic white adults. The association between lip cancer and the ACE inhibitor lisinopril, which also is photosensitizing, was characterized as "equivocal." And atenolol, a beta-adrenergic blocker that is not photosensitizing, was not linked to a higher risk.

Dr. Friedman and his colleagues used prescription data from the Kaiser Permanente pharmacy database and information from its cancer registry to perform a case-control study examining the relationship between the four classes of antihypertensive medications and lip cancer. They assessed the period from 1994 through 2008. The database includes an ethnically and socioeconomically diverse population of residents in the San Francisco and central valley regions of California.

There were few cases of lip cancer among nonwhite patients, so the analysis was restricted to white patients. Those with human immunodeficiency virus infection and those taking immunosuppressants after receiving organ transplants also were excluded because these factors were likely to be confounders.

The study population comprised 712 patients with lip cancer and 22,904 age-matched control patients. Nearly all malignancies were squamous cell. As expected, cigarette smokers in both study groups were more likely than nonsmokers to develop lip cancer.

The risk of developing lip cancer showed a dose-response relationship with the use of certain antihypertensive drugs, with the risk increasing as the duration of drug use increased. For patients treated with hydrochlorothiazide for 5 years or more, the odds ratio of developing lip cancer was 4.22. The OR for the combination drug hydrochlorothiazide-triamterene was 2.82, and the OR for nifedipine was 2.50. The OR was of borderline significance for lisinopril (1.42).

In contrast, for patients treated with atenolol for 5 years or more, the risk of developing lip cancer was reduced, with an odds ratio of 0.54, the investigators reported (Arch. Intern. Med. 2012 Aug. 6 [doi:10.1001/archinternmed.2012.2754]).

It should not be surprising that previous large clinical trials of these drugs’ efficacy failed to find an association with lip cancer, because of the rarity of the malignancy, they added.

For example, one study of antihypertensive medications involved more than 33,000 patients followed for a mean of 5 years. And after the investigators excluded the nonwhite patients, adjusted for the much lower incidence of lip cancer in women (who comprised half of the study population) than in men, and considered the low background incidence of the malignancy, they found that only seven lip cancers would have been expected to be detected in all the treatment groups combined, reported Dr. Friedman, also of the department of health research and policy, Stanford (Calif.) University, and his associates.

"Although the relatively high odds ratios, the evidence for specificity, and the biological mechanism are consistent with a causal relationship, causality cannot usually be established by a single observational study such as ours. Further investigations are needed to confirm and characterize relationships between photosensitizing antihypertensive agents and lip cancer," the researchers noted.

The study was limited because the researchers were unable to account for patients’ sun exposure, which is the most important factor contributing to lip cancer risk. "However, it does not seem likely that users of the antihypertensive drugs associated with lip cancer experience a great deal more sun exposure than nonusers or than users of atenolol," they wrote.

This study was supported by the National Cancer Institute. Dr. Friedman reported ties to Allergan, and his associates reported ties to Genentech, Merck, Sanofi-Aventis, and Takeda.

ORLANDO – Oral isotretinoin holds potential as a bridge therapy for cancer patients who develop severe rashes during treatment, according to Dr. Milan J. Anadkat.

Dermatologists can play an integral role here. "Most oncologists see these patients first, and most oncologists are not enrolled in the iPledge program," said Dr. Anadkat of the division of dermatology at Washington University in St. Louis.

He noted that all treatment options are off label because there are no Food and Drug Administration–approved agents to treat chemotherapy-related cutaneous toxicities.

Getting patients through rashes that occur within a week or two of beginning targeted chemotherapy is important, as patients who develop the greatest reactions tend to have cancers that respond best to treatment, said Dr. Anadkat at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery. For this reason, the management of these patients is more complicated than simple drug cessation.

"The problem with just taking them off the drug is that they have cancer. Ultimately, the big goal here is treating the cancer, not avoiding the rash," he said.

Tetracycline or doxycycline can also reduce the severity of the rash, but the timing of administration is important. Better outcomes are associated with prophylaxis that is timed with the initiation of EGFR (epidermal growth factor receptor) inhibitors (Cancer 2008;113:847-53). "Waiting for the rash to appear is not the time to give it. It makes a difference if you give at day 0, not in terms of incidence but in the severity of the rash," he said.

Educate patients that the rash typically appears in an estimated 60%-90% of people within 8-10 days of EGFR inhibitor initiation, with a peak presentation at 2-4 weeks. "Bridging them through with something as effective as isotretinoin is useful," said Dr. Anadkat.

The rash generally appears on the face and upper trunk, but be careful not to confuse the presentation with a photo-exposure phenomenon.

Although some oncologists will describe the skin eruptions as "acnelike," histology will show mixed inflammatory infiltrate and follicular rupture. For this reason, "topical acne medications do very little," Dr. Anadkat said. Also, rule out infection, except when patients present with pustules on their arms, legs, or other non–EGFR receptor areas.

EGFR inhibitors can cause inflammatory alopecia, eyelash trichomegaly, and periungual and nail alterations.

About one in six patients will develop periungual or nail abnormalities, typically on their first finger or toe. These effects can be painful, Dr. Anadkat said. Culture is mandatory to rule out superinfection.

Again, the approach is to get patients through the adverse events with petroleum jelly, high-dose topical steroids, or oral tetracyclines. "Tumor markers are going down; [oncologists] are not going to want to stop chemotherapy for a painful thumb or toe," he said. "I recommend antimicrobial soaks with bleach or vinegar to prevent paronychia superinfection."

Dry, itchy skin is another concern with long-term EGFR inhibitor treatment. Histology shows "stark differences" in the stratum corneum. "This is the No. 1 side effect for patients on long-term EGFR – 3 months or longer; [it is] not a grade 3 or higher toxicity, but it is annoying."

Investigators compared oral minocycline and topical tazarotene prophylaxis in a study of 48 patients with cetuximab associated rash (J. Clin. Oncol. 2007:25:5390-6). Although oral minocycline was associated with reduced lesion counts, topical tazarotene yielded no significant benefit. "Again, this is not acne," Dr. Anadkat said.

He disclosed being a consultant or speaker for AstraZeneca, Bristol-Myers Squibb, Eisai, Genentech, and ImClone regarding strategies for managing skin toxicities from chemotherapy. He has never prescribed chemotherapy agents.

ORLANDO – Oral isotretinoin holds potential as a bridge therapy for cancer patients who develop severe rashes during treatment, according to Dr. Milan J. Anadkat.

Dermatologists can play an integral role here. "Most oncologists see these patients first, and most oncologists are not enrolled in the iPledge program," said Dr. Anadkat of the division of dermatology at Washington University in St. Louis.

He noted that all treatment options are off label because there are no Food and Drug Administration–approved agents to treat chemotherapy-related cutaneous toxicities.

Getting patients through rashes that occur within a week or two of beginning targeted chemotherapy is important, as patients who develop the greatest reactions tend to have cancers that respond best to treatment, said Dr. Anadkat at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery. For this reason, the management of these patients is more complicated than simple drug cessation.

"The problem with just taking them off the drug is that they have cancer. Ultimately, the big goal here is treating the cancer, not avoiding the rash," he said.

Tetracycline or doxycycline can also reduce the severity of the rash, but the timing of administration is important. Better outcomes are associated with prophylaxis that is timed with the initiation of EGFR (epidermal growth factor receptor) inhibitors (Cancer 2008;113:847-53). "Waiting for the rash to appear is not the time to give it. It makes a difference if you give at day 0, not in terms of incidence but in the severity of the rash," he said.

Educate patients that the rash typically appears in an estimated 60%-90% of people within 8-10 days of EGFR inhibitor initiation, with a peak presentation at 2-4 weeks. "Bridging them through with something as effective as isotretinoin is useful," said Dr. Anadkat.

The rash generally appears on the face and upper trunk, but be careful not to confuse the presentation with a photo-exposure phenomenon.

Although some oncologists will describe the skin eruptions as "acnelike," histology will show mixed inflammatory infiltrate and follicular rupture. For this reason, "topical acne medications do very little," Dr. Anadkat said. Also, rule out infection, except when patients present with pustules on their arms, legs, or other non–EGFR receptor areas.

EGFR inhibitors can cause inflammatory alopecia, eyelash trichomegaly, and periungual and nail alterations.

About one in six patients will develop periungual or nail abnormalities, typically on their first finger or toe. These effects can be painful, Dr. Anadkat said. Culture is mandatory to rule out superinfection.

Again, the approach is to get patients through the adverse events with petroleum jelly, high-dose topical steroids, or oral tetracyclines. "Tumor markers are going down; [oncologists] are not going to want to stop chemotherapy for a painful thumb or toe," he said. "I recommend antimicrobial soaks with bleach or vinegar to prevent paronychia superinfection."

Dry, itchy skin is another concern with long-term EGFR inhibitor treatment. Histology shows "stark differences" in the stratum corneum. "This is the No. 1 side effect for patients on long-term EGFR – 3 months or longer; [it is] not a grade 3 or higher toxicity, but it is annoying."

Investigators compared oral minocycline and topical tazarotene prophylaxis in a study of 48 patients with cetuximab associated rash (J. Clin. Oncol. 2007:25:5390-6). Although oral minocycline was associated with reduced lesion counts, topical tazarotene yielded no significant benefit. "Again, this is not acne," Dr. Anadkat said.

He disclosed being a consultant or speaker for AstraZeneca, Bristol-Myers Squibb, Eisai, Genentech, and ImClone regarding strategies for managing skin toxicities from chemotherapy. He has never prescribed chemotherapy agents.

ORLANDO – Oral isotretinoin holds potential as a bridge therapy for cancer patients who develop severe rashes during treatment, according to Dr. Milan J. Anadkat.

Dermatologists can play an integral role here. "Most oncologists see these patients first, and most oncologists are not enrolled in the iPledge program," said Dr. Anadkat of the division of dermatology at Washington University in St. Louis.

He noted that all treatment options are off label because there are no Food and Drug Administration–approved agents to treat chemotherapy-related cutaneous toxicities.

Getting patients through rashes that occur within a week or two of beginning targeted chemotherapy is important, as patients who develop the greatest reactions tend to have cancers that respond best to treatment, said Dr. Anadkat at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery. For this reason, the management of these patients is more complicated than simple drug cessation.

"The problem with just taking them off the drug is that they have cancer. Ultimately, the big goal here is treating the cancer, not avoiding the rash," he said.

Tetracycline or doxycycline can also reduce the severity of the rash, but the timing of administration is important. Better outcomes are associated with prophylaxis that is timed with the initiation of EGFR (epidermal growth factor receptor) inhibitors (Cancer 2008;113:847-53). "Waiting for the rash to appear is not the time to give it. It makes a difference if you give at day 0, not in terms of incidence but in the severity of the rash," he said.

Educate patients that the rash typically appears in an estimated 60%-90% of people within 8-10 days of EGFR inhibitor initiation, with a peak presentation at 2-4 weeks. "Bridging them through with something as effective as isotretinoin is useful," said Dr. Anadkat.

The rash generally appears on the face and upper trunk, but be careful not to confuse the presentation with a photo-exposure phenomenon.

Although some oncologists will describe the skin eruptions as "acnelike," histology will show mixed inflammatory infiltrate and follicular rupture. For this reason, "topical acne medications do very little," Dr. Anadkat said. Also, rule out infection, except when patients present with pustules on their arms, legs, or other non–EGFR receptor areas.

EGFR inhibitors can cause inflammatory alopecia, eyelash trichomegaly, and periungual and nail alterations.

About one in six patients will develop periungual or nail abnormalities, typically on their first finger or toe. These effects can be painful, Dr. Anadkat said. Culture is mandatory to rule out superinfection.

Again, the approach is to get patients through the adverse events with petroleum jelly, high-dose topical steroids, or oral tetracyclines. "Tumor markers are going down; [oncologists] are not going to want to stop chemotherapy for a painful thumb or toe," he said. "I recommend antimicrobial soaks with bleach or vinegar to prevent paronychia superinfection."

Dry, itchy skin is another concern with long-term EGFR inhibitor treatment. Histology shows "stark differences" in the stratum corneum. "This is the No. 1 side effect for patients on long-term EGFR – 3 months or longer; [it is] not a grade 3 or higher toxicity, but it is annoying."

Investigators compared oral minocycline and topical tazarotene prophylaxis in a study of 48 patients with cetuximab associated rash (J. Clin. Oncol. 2007:25:5390-6). Although oral minocycline was associated with reduced lesion counts, topical tazarotene yielded no significant benefit. "Again, this is not acne," Dr. Anadkat said.

He disclosed being a consultant or speaker for AstraZeneca, Bristol-Myers Squibb, Eisai, Genentech, and ImClone regarding strategies for managing skin toxicities from chemotherapy. He has never prescribed chemotherapy agents.