Combination therapy proves effective in controlling melanoma

February 1, 2008

According to a recent study, a combination therapy of 5 percent imiquimod cream and intralesional interleukin-2 caused a regression of cutaneous and subcutaneous malignant melanoma lesions, as well as suppressed the advancement in accessible metastases.

Key Points

London - Effectively treating metastatic skin disease in patients with malignant melanoma is a very challenging task. Patients often must endure repeated treatments with various modalities in an attempt to control spread of the disease.

A combination therapy of topical imiquimod and intralesional interleukin-2 proves to be effective and shows great promise in controlling metastatic cutaneous and subcutaneous malignant melanoma, according to the results of a recent study.

A team of researchers at St. George's University of London, consisting of Miss Deborah Green; Mark Bodman-Smith, Ph.D.; Mr. Mike Fischer; and professor Angus Dalgleish, M.B.B.S., B.Sc., M.D., F.R.C.P., R.A.C.P., F.R.C.path., F.MedSci, conducted a study to evaluate the effects of a combined therapy consisting of topical imiquimod, and in selected lesions, intralesional interleukin-2 in 13 patients with cutaneous and subcutaneous metastatic melanoma disease, that were resistant to other treatment modalities.

Following this local therapy, intralesional interleukin-2 was injected up to three times a week into selected lesions, dosed at 0.1 ml per lesion at a concentration of 3.6 MIU ml with a total of 1 ml being given at each session.

The treated lesions were then assessed individually at three-month intervals.

A total of 182 lesions were treated. Of these, 137 were purely cutaneous and 41 were subcutaneous lesions.

"We saw that the combination of imiquimod and interleukin-2 was effective in controlling the cutaneous and subcutaneous metastases.

"A clinical response was seen in 92 lesions, and 74 of these demonstrated a complete response. Ninety-one percent of these complete response lesions were purely cutaneous lesions," the authors say.

Ten of the 13 patients recruited into the study completed 12 weeks or more of treatment, and therefore met the criteria for analysis. Of the 10 patients completing treatment, five had a mixture of cutaneous and subcutaneous disease, and five had purely subcutaneous disease.

The investigative team noticed that new lesions did appear throughout the course of treatment. However, patients with cutaneous disease demonstrated a marked slowing of the appearance of new cutaneous lesions with this novel treatment. Furthermore, none of the cutaneous lesions that responded reappeared upon the cessation of treatment.

"Topical imiquimod is often sufficient to elicit a response in purely cutaneous lesions. Yet, the combination of imiquimod with intralesional interleukin-2 increased the response rates in the subcutaneous lesions as well as in the cutaneous lesions, which are otherwise refractory to other treatment modalities," the authors say.

Until now, the treatment and management of nonsurgically resectable melanoma metastases has been less than optimal, as these lesions are multiple and recur often.

"Our results show that for patients with in-transit metastases of malignant melanoma, therapy with the combination of topical imiquimod with the addition of intralesional interleukin-2 for selected lesions can be effective and serve as a viable treatment option in clearing the majority of accessible cutaneous lesions.

"We saw that in five patients with mixed disease, 51 percent of cutaneous lesions showed a clinical response, with over 49 percent exhibiting a complete response," the authors say.

In the majority of cases, responses in purely cutaneous lesions were seen with the sole use of topical imiquimod.

According to the report, because intralesional interleukin-2 was administered systematically beginning at week four, the overall therapeutic effect seen is very likely due to the combined effectiveness of both drugs.

"No subcutaneous lesions larger than approximately 1 cm in diameter responded without the intensive schedule of intralesional interleukin-2 injections. Where stable disease or a partial response of subcutaneous lesions occurred, suspension of the intralesional interleukin-2 injections invariably resulted in notable progression within a matter of weeks," the authors say.

In general, the treatment was well-tolerated by the patients, and none of the patients withdrew from the study due to adverse events.