PRURITUS FROM TARGETED CANCER DRUGS 

MIAMI BEACH, Florida — A high number of cancer patients — 20% — treated with an epidermal growth-factor inhibitor or a mammalian target of rapamycin (mTOR) develop pruritus, 2 new studies reveal.

"It's important to recognize the risk and to treat it adequately," lead investigator of both studies, Alyx Rosen, told Medscape Medical News.

Persistent scratching left untreated can lead to unsightly and painful exfoliation, infection, and other adverse events that can interfere with activities of daily living.

"Prevention strategies are most important," Rosen said here at the American Academy of Dermatology 71st Annual Meeting. "A lot of patients are unprepared for the dermatologic side effects."

Rosen, a fourth-year medical student at Albert Einstein College of Medicine in the Bronx, New York, said patients should apply emollients to their skin and be encouraged not to scratch.

To objectively quantify risk for pruritus, the researchers conducted 2 studies — one of cetuximab (an epidermal growth-factor inhibitor) and the other of everolimus and temsirolimus (mTORs). They searched PubMed and Web of Science databases for prospective monotherapy trials with adverse-event data. They also searched relevant abstracts presented at American Society of Clinical Oncology annual meetings from 2004 to 2012.

The researchers found that each agent causes significantly more pruritus than placebo.

In addition, "we determined that there is a significant difference between everolimus and temsirolimus" in the risk for all-grade pruritus (P < .001), said Rosen, who was a clinical research fellow at the Memorial Sloan-Kettering Cancer Center in New York City at the time of the study. The types of trials included in the cetuximab meta-analysis precluded a relative risk calculation.

Table. Incidence and Relative Risk for Pruritus

Variables	Cetuximab (95% CI)	Everolimus (95% CI)	Temsirolimus (95% CI)
No. of patients	217	451	186
No. of trials	6	4	35
All-grade incidence, %	18.2 (10.8–28.8)	14.1 (11.1–17.6)	37.7 (20.9–58.0)
Relative risk	N/A	1.91 (1.01–3.63)*	5.01 (2.68–9.37)†

*P = .047; †P < .001

Milan   Anadkat, MD, from the Washington University School of Medicine in St. Louis, Missouri, who was asked by Medscape Medical News to comment on the study, said that "there is an underappreciation of how pruritus affects quality of life. These studies should highlight the burden on these patients."

Determining the precise cause of itch is a challenge for dermatologists because it can be multifactorial, Dr. Anadkat explained. With a patient treated with cetuximab, for example, pruritus can be associated with a papular pustular rash or dry skin. "mTOR inhibitors can also cause a fairly nondescript exanthematous itch," he noted.

"For dermatologists, our role is providing palliative care," Dr. Anadkat said. "That's where we are useful" in this patient population.

The cetuximab meta-analysis involved patients with multiple cancer types, including squamous cell, bronchoalveolar, hepatocellular, esophageal or gastric, nonsmall-cell lung, and salivary gland carcinoma. The everolimus and temsirolimus studies involved patients with kidney, lymphoma, endometrial, pancreatic, gastric, neuroendocrine, and head and neck squamous cell cancers.

Although these targeted treatments generally cause less overall toxicity than traditional radiation or chemotherapy, adverse cutaneous effects — including pruritus — could potentially hinder their use, Rosen said. "More study is required...to prevent suboptimal dosing and to maintain patient quality of life."

Further research could identify specific factors that contribute to pruritus and identify patients at greatest risk, Rosen noted.

The researchers have disclosed no relevant financial relationships. Dr. Anadkat reports working as a consultant for Bristol Myers Squibb, the maker of cetuximab.

American Academy of Dermatology (AAD) 71st Annual Meeting: Abstracts 6967 and 7000. Presented March 3, 2013.