Co-immunotherapy with interleukin-2 and taurolidine for progressive metastatic melanoma.
BACKGROUND
Recombinant interleukin-2(rIL-2) therapy in metastatic melanoma is limited by toxicities, particularly vascular leak syndrome(VLS). Taurolidine potentiates the anti-neoplastic effects of IL-2 while reducing its associated endothelial cell dysfunction in experimental settings. We hypothesized that co-administration of rIL-2 with taurolidine could enhance tolerability without weakening effectiveness.


METHODS
Eleven patients with progressive metastatic melanoma received high-dose rIL-2 with co-infusion of taurolidine. Patients were monitored for the development of toxicities and evidence of response.


RESULTS
Ten patients tolerated twenty-nine courses of high-dose rIL-2 without dose-reduction. Most toxicities were low-grade. No patient developed VLS. Seven patients died from disease progression. Two had complete clinical and radiological responses to treatment. Two patients remain alive despite evidence of disease progression a mean of 17.5 months after diagnosing metastatic disease.


CONCLUSIONS
Co-administration of taurolidine with high-dose rIL-2 in stage IV melanoma patients appears to greatly enhance the tolerability of this regime without diminishing its therapeutic value.
O'Brien
G C
GC
Dept of Academic Surgery, Cork University Hospital and NUI.
Cahill
R A
RA
Bouchier-Hayes
D J
DJ
Redmond
H P
HP
D000328:Adult; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D007494:Ireland; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D013654:Taurine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013829:Thiadiazines / Q000627:therapeutic use*
D004338:Drug Combinations; D007376:Interleukin-2; D013829:Thiadiazines; D013654:Taurine; C012566:taurolidine