Treatment to reduce plasma levels of arginine, an amino acid that contributes to the growth of melanoma, may be a safe and effective approach to controlling metastatic melanoma, according to the results of phase I and II studies published in the Journal of Clinical Oncology .
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. The prognosis for patients diagnosed with metastatic melanoma is poor since this disease typically does not respond well to standard therapies.
A newer approach being explored for the treatment of metastatic melanoma involves reducing plasma levels of the amino acid arginine. Arginine is a nonessential amino acid for humans; this means that it can be synthesized by the body and therefore does not need to be consumed in the diet. In contrast to normal cells, however, many melanoma cells cannot synthesize arginine and rely on external sources of arginine for growth. Thus, researchers speculate that reducing plasma levels of arginine may slow the growth of melanoma and have only a limited effect on normal cells.
To evaluate the effect of treatment with an enzyme that degrades arginine (arginine deiminase), researchers conducted a phase I clinical trial among 15 patients in the US and a phase I to II clinical trial among 24 patients in Italy. All patients had inoperable metastatic melanoma.
Treatment greatly reduced plasma arginine. Levels were lowered from roughly 130 mmol/L to less than 2 mmol/L. There were no serious adverse effects of treatment. The 24 patients enrolled in the phase I to II study had the following responses:
- 6 patients (25%) responded to treatment.
- 5 patients experienced a partial disappearance of detectable melanoma.
- 1 patient experienced a complete disappearance of detectable melanoma.
The researchers conclude that elimination of plasma arginine was well tolerated by patients with metastatic melanoma and may be effective against cancer. Further testing in a larger population of patients is warranted.
Patients with melanoma may wish to talk with their doctor about the risks and benefits of participating in a clinical trial further evaluating this or other therapeutic options. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (www.cancer.gov)and www.cancerconsultants.com.
Reference: Ascierto PA, Scala S, Castello G et al. Pegylated Arginine Deiminase Treatment of Patients with Metastatic Melanoma: Results from Phase I and II Studies. Journal of Clinical Oncology. 2005;7660-7668.
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