A phase II trial of low-dose total body irradiation and subcutaneous interleukin-2 in metastatic melanoma.

BACKGROUND AND PURPOSE

Our own experimental data suggests a therapeutic synergism between low-dose total body irradiation (LTBI) and interleukin-2 (IL-2).

PATIENTS AND METHODS

Forty-five patients received a maximum of 2 cycles of high dose subcutaneous (s.c.) IL-2 and LTBI. One treatment cycle included 5 weeks treatment followed by 2 weeks break and composed of a single radiation fraction 0.1 Gy on days 1, 8, 22 and 30 and IL-2: 18 MU x 2 daily s.c. on days 2 to 5 and days 16-19 as well as 9 MU x 2 daily s.c. on days 9-12 and 31-34. In 17 patients, flow cytometric analyses of the various subpopulations of immune cells were done on blood samples before the first LTBI fraction and 24h after LTBI as well as after the first week of treatment.

RESULTS

Two patients (4.4%) had a partial response (PR) and 13 patients (29%) had stable disease (SD). The duration of the partial remission and stable disease did not exceed 3 months. The median overall survival was 5.8 months (95% CI, 4-8 months). Thirty-four of the 58 treatment cycles (74%) were given in 100% of the intended dose without modification or delay. The dose was modified in 15 cycles (26%) because of progression (6), liver toxicity (3), CNS toxicity (2), thrombocytopenia (1), lung morbidity (1) and itching (1). There were no treatment-related deaths. Flowcytometry data showed a significant increase in the percentage of cells carrying the beta chain of IL-2 receptor (CD122+), a significant increase in the percentage of NK cells (CD56+ cells) as well as a significant reduction in the percentage of B cells (CD20+) and monocytes (CD14+).

CONCLUSIONS

This LTBI and IL-2 regimen was well tolerated, however it cannot be recommended because of its low clinical efficacy. No indication of increased efficacy or altered toxicity was seen using LTBI.