Histamine Plus Interleukin-2 Produces Responses in Advanced Melanoma

Histamine Plus Interleukin-2 Produces Responses in Advanced Melanoma

According to a recent article published in the

Journal of Clinical Oncology, a histamine agent (dihydrochloride) added to interleukin-2 may improve survival time for some patients with metastatic melanoma.

Melanoma is a cancer of the skin that usually begins in the form of a mole. The cancer can grow deep into the skin and spread to different parts of the body through blood or lymph vessels. It usually spreads first to lymph nodes that are near the site of cancer origin and when advanced, can spread to organs and other lymph nodes throughout the body. Treatment for advanced or metastatic melanoma may consist of surgery, radiation, chemotherapy and/or biologic therapy. However, the prognosis for patients diagnosed with this disease is poor, as melanoma typically does not respond well to standard therapies.

One type of biologic therapy that has shown promise against this type of cancer is interleukin-2 (IL-2). Interleukin-2 is a cytokine, a substance that is naturally produced by the body’s immune system. In some cases, the use of interleukin-2 as a therapy can help stimulate the immune system and fight the cancer. In the case of metastatic melanoma, intravenous interleukin-2 has produced anti-cancer response rates of 15% to 20%; however, the side effects of this treatment often limit its use. Efforts to minimize these side effects by developing innovative ways to deliver interleukin-2 are ongoing.

In previous studies, researchers have attributed the presence of a substance called ROS (reactive oxidative species) within malignant tumors to immune suppression. This immune suppression inhibits the body from fighting the cancer. Histamine has been shown to block the formation of ROS and potentially increase the body’s immune response to a malignant tumor. Dihydrochloride is one type of histamine being used in research for the treatment of advanced melanoma.

Researchers recently conducted a multi-center clinical trial to determine the efficacy of the addition of dihydrochloride to subcutaneous IL-2 in 305 patients with metastatic melanoma. In this trial, all patients were treated with subcutaneous IL-2 on an outpatient basis. In addition, half of the patients received dihydrochloride. Disease progression occurred in 38% of patients who received IL-2 alone and 20% of patients who received IL-2 and dihydrochloride. The overall survival difference was only slightly better for patients receiving both IL-2 and histamine (272 days) compared to 245 days for patients receiving only IL-2. However, survival for patients whose cancer had spread to the liver was significantly improved by histamine and IL-2 at 283 days compared to 154 days for IL-2 alone. Side effects and therapy tolerance were similar for both groups.

These results are promising for the treatment for metastatic melanoma, as dihydrochloride and subcutaneous IL-2 appears to be well-tolerated and may potentially increase survival time, especially for patients with liver metastasis. Future clinical trials may further define the role of histamine with IL-2 for the treatment of advanced melanoma.

Patients with metastatic melanoma may wish to speak with their physician about the risks and benefits of participating in a clinical trial evaluating dihydrochloride with IL-2 or other novel therapeutic approaches. Two sources of information regarding ongoing clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute

www.eCancerTrials.com. eCancerTrials.com also provides personalized clinical trial searches on behalf of patients. (

Journal of Clinical Oncology, Vol 20, No 1, pp 125-133, 2002)

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