Continuous interleukin-2 and tumor-infiltrating lymphocytes as treatment of advanced melanoma. A national biotherapy study group trial.
Melanoma metastases were harvested from 82 patients for the purpose of growing and expanding tumor-infiltrating lymphocytes (TIL). Tumor tissue cell suspensions were incubated with interleukin-2 (IL-2), followed by repeated exposure to tumor antigen with or without OKT3 monoclonal antibody (MoAb). Initial growth success was achieved in 56 of 82 cultures (72%). Efforts were made to expand 26 of these 56 cultures for therapeutic TIL; 23 of 26 early cultures (88%) were successfully expanded for in vivo therapy. It took a mean of 78.5 +/- 25.4 days to grow sufficient TIL for treatment. Therapy included cyclophosphamide (1 g/m2) on day 1, followed by a 96-hour continuous infusion of IL-2 (18 x 10(6) IU/m2/d) on days 2 to 5, and approximately 10(11) (mean 1.49 +/- 0.93 x 10(11)) TIL on day 2. Patients who responded received monthly IL-2 as a 96-hour infusion. Median patient age was 45 years of age. Sixty-seven percent of the patients were men. Performance status was 0 to 1 in 77% of patients. Thirty-four percent of the patients had liver metastases. The usual IL-2 toxicities were seen. Response rate for 21 patients was 24% (95% confidence interval, 10% to 49%). One complete response was achieved with cells 98% CD4+; four partial responses were achieved with cells 80%, 94%, 98%, and 98% CD8+, respectively. Four of eight patients who received TIL, which had never been stimulated with OKT3, had tumor response. The authors conclude that a treatment plan for IL-2/TIL is technically difficult, costly, and effective for only a minority of patients. Overall, clinical results are not clearly superior to those obtained with other IL-2 regimens.
Dillman
R O
RO
Hoag Cancer Center, Newport Beach, CA 92658.
Oldham
R K
RK
Barth
N M
NM
Cohen
R J
RJ
Minor
D R
DR
Birch
R
R
Yannelli
J R
JR
Maleckar
J R
JR
Sferruzza
A
A
Arnold
J
J
D000328:Adult; D003131:Combined Modality Therapy; D003365:Costs and Cost Analysis; D003520:Cyclophosphamide / Q000008:administration & dosage; D004802:Eosinophilia / Q000209:etiology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D007902:Length of Stay / Q000191:economics; D016246:Lymphocytes, Tumor-Infiltrating / Q000637:transplantation*; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D012074:Remission Induction; D012878:Skin Neoplasms / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D003520:Cyclophosphamide