title: Continuous infusion interleukin-2 and tumor-derived activated cells as treatment of advanced solid tumors: a National Biotherapy Study Group Trial.
abstract: Metastases from patients with solid tumors were harvested from 196 patients for the purpose of growing tumor-derived activated cells (TDAC). Cells were prepared from autologous tumor cultures by incubation with Interleukin-2 (IL-2) followed by repeated exposure to tumor antigen and/or anti-CD3 monoclonal antibody. Initial growth success was achieved in 66%; 45/56 (80%) of these early cultures were subsequently expanded for in vivo therapy. It took a mean of 69.4 +/- 24.0 days to grow TDAC for treatment. Thirty-eight patients were treated with cyclophosphamide (1 g/m2) on day one followed by a 96-hour continuous infusion of IL-2 (18 x 10(6) IU/m2/day) on days 2-5 and approximately 10(11) TDAC on day 2. Patients subsequently received monthly IL-2 as a 96-hour constant infusion if their cancers were stable or regressing. Median age was 51 yrs; 58% were male. Performance status was 0-1 in 64%, 29% had lung metastases; 34% had liver metastases. The usual IL-2 toxicities were seen. Responses were seen only in 1/38 patients (3%); a partial response in a patient with lymphoma. Forty-two percent were stable 90 days post-treatment, the rest were progressive or inevaluable. We conclude that a treatment plan for IL-2/TDAC is technically difficult, costly, and not practical under these conditions. Clinical results to date are not clearly different than those obtained with other IL-2 regimens.
authors.affiliation: Biological Therapy Institute, Franklin, TN 37065-1700.
authors.forename: R K
authors.initials: RK
authors.lastname: Oldham
authors.forename: R O
authors.initials: RO
authors.lastname: Dillman
authors.forename: J R
authors.initials: JR
authors.lastname: Yannelli
authors.forename: N M
authors.initials: NM
authors.lastname: Barth
authors.forename: J R
authors.initials: JR
authors.lastname: Maleckar
authors.forename: A
authors.initials: A
authors.lastname: Sferruzza
authors.forename: R J
authors.initials: RJ
authors.lastname: Cohen
authors.forename: D R
authors.initials: DR
authors.lastname: Minor
authors.forename: L
authors.initials: L
authors.lastname: Spitler
authors.forename: R
authors.initials: R
authors.lastname: Birch
mesh_terms: D000328:Adult; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D016219:Immunotherapy, Adoptive / Q000191:economics; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D015993:Life Tables; D016246:Lymphocytes, Tumor-Infiltrating / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D014182:Transplantation, Autologous
chemical_list: D007155:Immunologic Factors; D007376:Interleukin-2; D003520:Cyclophosphamide