New Data Reported on Melanoma, Cutaneous T-cell Lymphoma, Basal Cell Carcinoma, and Cancer Treatment Side Effects 


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At the recent American Academy of Dermatology 71st Annual Meeting in Miami Beach, researchers presented interesting findings regarding melanoma and other skin cancers. The ASCO Post brings you the following news briefs on these topics.

Melanoma Incidence Decreases among Adolescents and Children

An analysis of Surveillance, Epidemiology and End Results (SEER) data showed that the incidence of melanoma in children and adolescents trended downward over the past decade (2000–2009).1 It is well established that melanoma incidence in adults has been increasing for 40 years, but trends among younger age groups have not been extensively studied.

Investigators from Case Western Reserve University, therefore, reviewed the SEER registries to calculate annual melanoma incidence rates in children and adolescents (age 0–19) from 1973 to 2009 and analyzed incidence trends in the recent decade from 2000 to 2009. They found that the incidence rate was < 0.2 per 100,000 persons in 1973, and then followed an inconsistent course to 1997, after which it rose to 0.7 in 2003 but declined to 0.5 by 2009. From 2000 to 2009, significant decreasing incidence trends were noted.

The decreasing incidence trend was most notable for the adolescent age group (age 15–19). The change was significant for male adolescents and for melanomas with good prognostic indicators, according to Laura B. Campbell, a medical student at Case Western Reserve University School of Medicine, Cleveland. She said the decline could be the result of increased adherence to sun protection in recent years as well as decreased time spent outdoors, with a shift to more time spent at indoor activities such as television- and electronics-based pursuits.

Preemptive Leucovorin May Ameliorate Pralatrexate Toxicity in CTCL

Patients with cutaneous T-cell lymphoma (CTCL) often experience a range of toxicities related to treatment with pralatrexate (Folotyn). In clinical trials and in clinical practice, mucositis and hematologic abnormalities are common dose-limiting toxicities of pralatrexate. Gastrointestinal side effects are also common. Adverse events are not relieved by B12 or folic acid. In a case series presented at the meeting by University of Pittsburgh researchers, CTCL patients who received preemptive leucovorin rescue along with pralatrexate were able to tolerate treatment.2

Preemptive leucovorin rescue (50 mg/m2) was given 24 hours after pralatrexate (30 mg/m2 weekly) as a salvage therapy to three patients who either failed to show improvement on prior therapies or experienced intolerable toxicity. Clinical responses were observed in all patients without the usual toxicity; no patients developed mucositis. The prophylactic use of leucovorin may alleviate pralatrexate-associated side effects without compromising clinical efficacy, reported Sara Story, MD, a cutaneous oncology clinical fellow at University of Pittsburgh Medical Center.

Melanoma Prognosis Improved by Screening

Seeing a dermatologist just once can mean the difference between melanoma diagnosed at an early stage, vs a later and more invasive stage, University of Pittsburgh investigators reported.3 The findings support growing evidence that general screening for melanoma—even once in a lifetime—is cost-effective in adults aged 50 and older.

In the study of 405 adults diagnosed with melanoma, patients with one prior visit to the dermatologist were about 30% more likely to present with noninvasive disease or melanomain situ and to have thinner lesions (approximately half the mean Breslow depth), compared with patients lacking a visit to the dermatologist prior to the diagnosis. 

Interestingly, the differences seemed to be largely attributable to a higher rate of self-detection of noninvasive lesions. Among patients who self-detected their cancer, 59% reported a previous dermatology consultation compared with 37% of those who did not (P = .007), said Michelle Cheng, MD, University of Pittsburgh School of Medicine. The findings highlight the critical role played by dermatologists in patient education, she noted. 

Tanning Bed Exposure and Melanoma Type

Patients with a history of exposure to artificial ultraviolet light via tanning beds had a higher risk for melanoma, but their average Breslow thickness at the time of diagnosis—especially for women—was lower than for patients with no history of exposure, a Polish study found.Barbara Borkowska, MD, and colleagues from the Department of Dermatology, CSK MSW, Warsaw, queried 113 patients with cutaneous melanoma about exposure to tanning beds throughout their lifetimes. The control group consisted of age- and sex-matched individuals.

Tanning bed exposure was highest for patients aged 30 to 39 (94.5%) and 40 to 49 (97.5%), compared to those < 29 (44.4%) and > 50 years of age (15%). The corresponding numbers in healthy controls were 23.2%, 26.4%, 16.2%, and 38.1%.

The average Breslow depth was 0.7 mm in women who declared tanning bed exposure and 1.8 mm in those without exposure, and the scores in men were 1.7 mm and 2.1 mm, respectively. Nodular melanoma was more than three times as common in patients who reported no exposure to artificial ultraviolet light as in patients claiming exposure. There was no correlation between the declared number of exposures and the Breslow depth.

Exposure to artificial ultraviolet light may be more likely to induce superficial spreading melanoma than nodular melanoma, the investigators suggested.

Neoadjuvant Vismodegib Enhances Cosmesis in Basal Cell Carcinoma

Resection of basal cell carcinoma tumors resulted in smaller cosmetic defects when patients received neoadjuvant vismodegib (Erivedge), in a small series reported by Stanford University investigators.5 The area of the defect was reduced by about 50% in patients who received 3 months of the hedgehog inhibitor vismodegib at 150 mg/d prior to surgical removal.

After a median 5.5 months of follow-up, no recurrences were seen in any of five patients given the drug prior to surgery for lesions in surgically challenging locations, such as the eyelid, reported Mina Ally, MBBS, a postdoctoral research fellow at Stanford School of Medicine, Stanford, California. The drug is approved for locally advanced and metastatic basal cell carcinoma, but no options exist to reduce surgical morbidity in challenging cases, she said.

The interim analysis included five patients with seven lesions treated for a median of 3.4 months. Mean estimated surgical defect decreased from 3 cm2 to 1.6 cm2 after preoperative treatment, a 46% reduction from baseline (P = .008). The downside was cost: For 3 months of treatment, the expenses exceeded $22,000 ($7,500 per month) and some patients needed more than 3 months of the high-priced biologic. 

Pruritus in Patients on Targeted Therapy

About one in five patients treated with inhibitors of the epidermal growth factor receptor or mammalian target of rapamycin (mTOR) develop pruritus, according to literature reviews performed by investigators from Memorial Sloan-Kettering Cancer Center in New York.6,7 The review evaluated 854 patients studied in 45 clinical trials of cetuximab (Erbitux), everolimus (Afinitor), and temsirolimus (Torisel).

In the cetuximab meta-analysis (based on six studies), the overall incidence of all-grade pruritus was 18.2%, whereas high-grade pruritus was observed in 2.0% of patients. In the studies of the mTOR inhibitors, the overall incidence of all-grade pruritus was 14.1% with everolimus and 37.7% with temsirolimus. For these drugs, the investigators were able to calculate a relative risk, vs placebo, which they found to be 1.91 and 5.01, respectively.

Prophylaxis, early detection, and proper management of symptoms are important for enhancing quality of life in these patients, said Alyx Rosen, a medical student at Albert Einstein College of Medicine and clinical research fellow at Memorial Sloan-Kettering Cancer Center, New York, who presented the studies. ■

Disclosure: Drs. Story, Cheng, and Borkowska, and Ms. Campbell, Ms. Rosen, and Ms. Ally reported no potential conflicts of interest.

References

1. Campbell LB, Bordeux J, Barnholtz-Sloan J, et al: Decreasing trends in melanoma incidence from 2000 to 2009 in children and adolescents. American Academy of Dermatology Annual Meeting. Abstract P6960. Presented March 2, 2013.

2. Story S, Koch E, Geskin L: Does preemptive leucovorin use compromise the efficacy of pralatrexate in CTCL? American Academy of Dermatology Annual Meeting. Abstract P7010. Presented March 3, 2013.

3. Cheng M, Moreau J, Ferris L, et al: The effect of full body skin examinations on the prognosis of melanoma. American Academy of Dermatology Annual Meeting. Abstract P6226. Presented March 3, 2013.

4. Borkowska B, Kardynal A, Sicinska J, et al: Invasiveness of melanoma in patients exposed to artificial UV light in tanning beds. American Academy of Dermatology Annual Meeting. Abstract P7126. Presented March 3, 2013.

5. Ally M, Aasi S, Oro A, et al: Vismodegib as an adjuvant to surgery for basal cell carcinomas. American Academy of Dermatology Annual Meeting. Late-breaking abstract. Presented March 2, 2013.

6. Rosen AC, Ensslin C, Wu S, et al:  Risk of pruritus in cancer patients treated with cetuximab: a systematic review of the literature and meta-analysis. American Academy of Dermatology Annual Meeting. Abstract P6967. Presented March 3, 2013.

7. Ensslin C, Rosen A, Wu S, et al: Risk of pruritus in cancer patients treated with inhibitors of the mammalian target of rapamycin, everolimus and temsirolimus: A systematic review of the literature and meta-analysis. American Academy of Dermatology Annual Meeting. Abstract P7000. Presented March 3, 2013.



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