title: Chemo-immunotherapy in patients with metastatic melanoma using sequential treatment with dacarbazine and recombinant human interleukin-2: evaluation of hematologic and immunologic parameters and correlation with clinical response.
abstract: We have treated 18 patients with metastatic malignant melanoma (MM) with high-dose IL-2 administered by continuous iv infusion in combination with dacarbazine (DTIC), and correlated the clinical response with various hematologic and immunologic parameters. Two regimens differing in the sequence of treatment were employed, and 1-6 treatment cycles were given, depending on patient response. Two patients had a complete response (CR, 46+m, 14m), two patients a partial response (PR, 16m,6m), one a minimal response and four had a stable disease lasting 2-7 months, thus the response rate (CR+PR) was 22%. None of the following parameters, tested prior to initiation of the therapy and 1-2 days after termination of each course of IL-2, correlated with the clinical response: WBC counts (total and differential), levels of blood CD4 and CD8 T cells, NK cells, monocytes and B cells, production of IL-1 and IL-1 inhibitor by monocytes, responsiveness to 3 mitogens, NK/LAK cell activity, and serum levels of IL-1 alpha, IL-2, soluble IL-2 receptor, and TNF alpha. The only prognostic parameter was the greater increase in the level of IL-2 receptor (Tac)-bearing lymphocytes in the responding patients after 1-3 cycles of IL-2. The data suggests that non-specific immune parameters have no prognostic value for patients undergoing IL-2-based immunotherapy.
authors.affiliation: Department of Oncology, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Isacson
authors.forename: E
authors.initials: E
authors.lastname: Kedar
authors.forename: V
authors.initials: V
authors.lastname: Barak
authors.forename: Z
authors.initials: Z
authors.lastname: Gazit
authors.forename: O
authors.initials: O
authors.lastname: Yurim
authors.forename: I
authors.initials: I
authors.lastname: Kalichman
authors.forename: H
authors.initials: H
authors.lastname: Ben-Bassat
authors.forename: S
authors.initials: S
authors.lastname: Biran
authors.forename: M
authors.initials: M
authors.lastname: Schlesinger
authors.forename: C R
authors.initials: CR
authors.lastname: Franks
mesh_terms: D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000276:immunology; D003606:Dacarbazine / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D008875:Middle Aged; D011994:Recombinant Proteins
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D011994:Recombinant Proteins; D003606:Dacarbazine