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Prophylactic Minocycline Keeps Cetuximab-Induced Rash at Bay

Web Exclusives

ORLANDO—Breakthrough pain in cancer patients can be managed easily and effectively with fentanyl pectin nasal spray, according to new data.

Minocycline, given before the start of treatment with cetuximab and chemoradiotherapy, plus topical pimecrolimus as needed, can reduce the severity of cetuximab-induced skin toxicity in patients with non–small-cell lung cancer (NSCLC), according to researchers from The Netherlands.

Cetuximab, a chimeric monoclonal antibody that binds to the extracellular domain of the epidermal growth factor receptor, has shown activity in patients with metastatic colorectal cancer, in addition to patients with NSCLC, but its potential for severe skin toxicity may cause some patients to abandon their treatment, said Wilma Uyterlinde, MANP, a nurse practitioner at the Netherlands Cancer Institute in Amsterdam.

In 2008, oncologists at the institute began to test the feasibility of combining cetuximab with concurrent chemoradiation in their patients with locally advanced NSCLC.

“We added cetuximab to our treatment because of the promising effects it was shown to have in colorectal cancer patients, and when we did so, we saw a lot of grade 3 skin toxicity, so we conferred with a dermatologist and an oncologist and we came up with a new protocol to see if we could reduce it,” said Uyterlinde, who specializes in thoracic oncology.

To test their protocol, the re searchers divided patients into two groups. All patients received cetuximab once weekly for 6 weeks along with daily cisplatin and radiotherapy. The 12 patients in group 1 were treated on demand after the appearance of an acneiform rash. The 14 patients in group 2 received prophylactic oral minocycline, 100 mg/day for 45 days, and, if necessary, topical pimecrolimus, 1%, twice daily.

Toxicity was scored according to the Common Toxicity Criteria for Adverse Events, version 3.0.

In the first group, 11 of 12 patients developed grade 2 or 3 acneiform rash, and one patient discontinued treatment because of the rash. In the second group, three of 14 patients developed grade 2 rash, and none of the patients developed grade 3 rash. This represents a significant difference be tween the groups (P = .001), Uyter linde said.

“In the cohort that did not get prophylactic treatment, we sometimes had to send patients to a specialized hospital for their skin toxicity because it was so bad, and we had to stop treatment with cetuximab because of the rash,” Uyterlinde noted. “If we give minocycline prophylactically and do not wait for the rash to appear, we manage to reduce the skin toxicity to a maximum of grade 2.”

She noted that controlling the acneiform rash did not compromise the effectiveness of cetuximab.

“It has not been proven that developing a rash means that cetuximab is working,” she said. “This is what they say, but it has never really been proven. That is a hypothesis. Controlling the rash works by a different mechanism and does not prevent the cetuximab from working on the tumor.”

The protocol has now become the institute’s standard for use in patients with other types of cancer undergoing treatment with cetuximab, she said

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Web Exclusives published on December 10, 2010 in Gynecologic Cancers