The CancerWeb Report, What's New In Cancer: October, 1996
Malignant Melanoma

• Type of lymphocytes found in tumor predicts response to interferon alpha - About 20% of patients with melanoma respond to treatment with interferon alpha. Interferon alpha not only has its own antitumor action but also modulates the immune response, including the activity of white blood cells that might be capable of attacking tumors. Results of several studies have suggested that those whose tumors show white cells infiltrating them have the best prognosis, but this has not been seen in other studies. A possible reason for this discrepancy is that it may be only certain types of white cells that are critical for an anticancer effect. An article by researchers at the Linkoping Hospital in Sweden, appearing in the September, 1996 issue of the British Journal of Cancer, reported that the CD4+ lymphocytes were the cells associated with the best response. Among 21 patients with distant metastatic melanomas, tumor regression occurred in 10 of 11 with moderate to high numbers of CD4+ cells in relation to tumor cells in the metastases, as examined by fine needle biopsy, when treated with interferon alpha. On the other hand, among those with few such cells, 9 of 10 had progressive disease. Twenty patients with regional metastases underwent surgery after only 1-3 weeks of interferon alpha because of the curative potential of resection. In this group also, the short-term response to interferon alpha followed the same pattern, with 7 of 10 patients who had high numbers of CD4+ cells showing marked response, compared to only 1 of 6 who had low numbers of these cells. (Hakansson, Brit J Cancer 74:670, 1996)

  Editor's Comment: - The CD4+ lymphocyte is a critical component of the immune response, and the prominent role played by its depletion in persons with AIDS has made it familiar to the general public. It is not surprising to find it also playing a role in antitumor action as suggested by this study. Immune therapy of tumors using interleukin-2 and primed tumor-infiltrating white cells is an ongoing treatment approach to several kinds of cancer. Immune function seems to play a prominent role in development and dissemination of melanoma.

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• Interferon and interleukin-2 combination, high response rate but severe toxicity - The combination of interferon alpha and interleukin-2 has given very variable responses in metastatic melanoma, with studies reporting anywhere from 0% to 44% response rates. The best responses were claimed for high doses (11.7 million IU interleukin and 3 million IU interferon per m2) given three times daily for 5 days per cycle (National Cancer Institute study, Rosenberg, J Clin Oncol 7:1863, 1989) . Doctors at the Rotterdam Cancer Institute in the Netherlands used this schedule and obtained a similar response rate of 41%. However, their report in the September, 1996 issue of the British Journal of Cancer, showed that this good response was achieved at the price of severe toxicity to the heart and central nervous system, in 41% and 28% of patients, respectively. Using a 3-day schedule, toxicity became manageable, but the response rate dropped to 20%. The authors' conclusions were that addition of interferon alpha did not improve the results achieved by interleukin-2 without producing unacceptable side-effects. (Kruit, Br J Cancer 74:951, 1996)