Factors associated with response to high-dose interleukin-2 in patients with metastatic melanoma.
OBJECTIVE
The present study attempted to identify characteristics that correlated with clinical response to interleukin (IL)-2 therapy in patients with metastatic melanoma.


METHODS
We retrospectively evaluated laboratory and clinical characteristics of 374 consecutive patients with metastatic melanoma treated with high-dose intravenous bolus IL-2 (720,000 IU/kg) from July 1, 1988, to December 31, 1999, at the Surgery Branch of the National Cancer Institute.


RESULTS
The overall objective response rate was 15.5%. Pretreatment parameters such as patient demographics, laboratory values, and prior therapy did not correlate with response; however, 53.6% of patients with only subcutaneous and/or cutaneous metastases responded, compared with 12.4% of patients with disease at other sites (P2 =.000001). During therapy, patients who were responders tended to have received more doses during course 1 (16.2 +/- 0.3 doses v 14.5 +/- 0.2 doses; P2 =.0095); however, when limited to patients who were able to complete both cycles of course 1, there was no statistically significant difference (P2 =.27). Responders had a higher maximum lymphocyte count immediately after therapy compared with nonresponders (P2 =.0026). The development of abnormal thyroid function tests and vitiligo after therapy was associated with response (thyroid-stimulating hormone, P2 =.01; free T4, P2 =.0049; vitiligo, P2 < 10(-6)), although thyroid dysfunction may have been related more to the length of IL-2 therapy than to response.


CONCLUSIONS
The presence of metastases only to subcutaneous and/or cutaneous sites, lymphocytosis immediately after treatment, and long-term immunologic side effects, especially vitiligo, were associated with antitumor response to IL-2 therapy.
Phan
G Q
GQ
Surgery Branch and Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA.
Attia
P
P
Steinberg
S M
SM
White
D E
DE
Rosenberg
S A
SA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D008218:Lymphocytosis / Q000139:chemically induced; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy / Q000556:secondary; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D016896:Treatment Outcome
D007376:Interleukin-2; D011994:Recombinant Proteins; D013972:Thyrotropin; D013974:Thyroxine