Manage Cancer Drugs

Rash as a Marker

There appears to be some evidence of a relationship between HER1/EGFR efficacy and associated rash severity. There have been at least 19 trials and additional compassionate use centers that have found the relationship of a positive correlation between rash and response/survival.

For example, in a Phase II study in 57 patients with non-small cell lung cancer, those with grade zero rashes had a median survival of 1.5 months, those with rash grade one had a median survival of 8.5 months, and those with rash grades two or three had a 19.6 month survival. In another study with erlotinib monotherapy, patients with a skin rash had significantly greater survival rates (approximately 80%) than those without skin rashes. In trials of cetuximab in patients with different cancer types, those who developed a rash lived substantially longer than those who did not.

There are also data supporting gefitinib and cetuximab. Many of the studies note a poorer clinical outcome in those patients without rash. These findings suggest that lack of a rash after a specific period of therapy may be an early indicator of treatment failure and the need for another treatment.

Rash Treatment

While receiving treatment with these agents, patients should be advised to moisturize dry body areas twice daily with a thick alcohol-free emollient. Patients should minimize sun exposure and wear a broad-spectrum sunscreen (SPF 15). Zinc oxide or titanium dioxide is preferred over chemical sunscreens. The following treatment interventions are suggested:

• Mild toxicity: topical hydrocortisone 1% to 2.5% cream or clindamycin 1% gel. The HER1/EGFR dose should not be adjusted;
• Moderate toxicity: topical hydrocortisone 2.5% cream, clindamycin 1% gel, or pimecrolimus 1% cream (Elidel) with doxycycline 100mg orally twice a day or minocycline 100mg orally twice a day. The HER1/EGFR dose should not be adjusted; or
• Severe toxicity: topical hydrocortisone 2.5% cream, clindamycin 1% gel, or pimecrolimus 1% cream (Elidel) with doxycycline 100mg orally twice a day or minocycline 100mg orally twice a day. Also add methylprednisolone dose pack.

Reduce the HER1/EGFR dose, if after two to four weeks the toxicities have not sufficiently abated, then the HER1/EGFR therapy should be interrupted. Once the skin reactions have resolved or diminished in severity, the HER1/EGFR dose may typically be restarted or re-escalated.

Results of a recent double-blind, placebo-controlled study suggest tetracycline may be effective in decreasing EGFR-associated rash severity and improving some quality-of-life parameters (e.g., irritation, burning, stinging).7 Remaining alert to these reactions in patients receiving HER1/EGFRs is important for monitoring treatment and managing patients. TH

Michele B. Kaufman is a freelance medical writer based in New York City.

References

1. Castillo L, Etienne-Grimaldi MC, Fischel JL, et al. Pharmacologic background of EGFR targeting. Ann Oncol. 2004;15(7):1007-1012.
2. Robert C, Soria JC, Spatz A et al. Cutaneous side effects of kinase inhibitors and blocking antibodies. Lancet Oncol. 2005;6(7):491-500.
3. Peréz-Soler R, Saltz L. Cutaneous adverse effects with HER1/EGFR-targeted agents: Is there a silver lining? J Clin Oncol. 2005;23(22):5235-5246.
4. Seiverling EV, Fernandez EM, Adams D. Epidermal growth factor receptor inhibitor associated skin eruption. J Drugs Dermatol. 2006;5(4)368-369. Available at http://findarticles.com/p/articles/ mi_m0PDG/ is_4_5/ai_n16361317Accessed August 7, 2007
5. Tyrosine Kinase Inhibitors. www.oncolink.com/treatment/article.cfm?c=12&s=90&id=268. Accessed August 7, 2007
6. Lynch TJ, Kim ES, Eaby B, et al. Epidermal growth factor receptor inhibitor-associated toxicities: An evolving paradigm in clinical management. Oncologist 2007;12(5):610-621.
7. Jatoi A, Rowland K, Sloan JA, et al. J Clin Oncol 2007; ASCO Annual Meeting Proceedings Part I. Vol. 25(18S);June 20:LBA9006.