Recombinant interleukin-2 (rIL-2) with flavone acetic acid (FAA) in advanced malignant melanoma: a phase II study.

Recombinant interleukin 2 (rIL-2) and flavone acetic acid (FAA) were used to treat 34 patients with progressing metastatic melanoma. Five patients had solely non-visceral disease and the median number of organ sites involved was two. Five doses of rIL-2 were given, the first dose intrasplenically via a femoral artery catheter with a further dose 4 h later i.v. and the other doses i.v. on alternate days. The rIL-2 dose was 11 x 10(6) Cetus units m-2; the day before rIL-2, FAA (4.8 G m-2) was given as a 6 h i.v. infusion, in order to enhance further killer cell activity. A total of three courses at 21-day intervals was planned and 74 courses in all were given. Despite the high dose of rIL-2 and the potential overlapping toxicity affecting blood pressure with the addition of FAA, side-effects were generally mild. There were only five episodes of grade 4 toxicity: one of ventricular tachycardia and four other episodes of transient biochemical or haematological disturbance. Grade 3 hypotension or hypertension occurred on 22 courses but again was transient. No patient required intensive care facilities. Five patients had tumour response, one being complete. Responses occurred in pulmonary and hepatic metastases, but mainly in non-visceral sites. Eleven patients remain alive at 6-17 months and in five there is no relapse or progression of disease. Despite the impressive results in animal tumour models, the addition of FAA to rIL-2 in the present study has not markedly improved results over rIL-2 alone.