title: A phase I-II study of dacarbazine in combination with outpatient interleukin-2 in metastatic malignant melanoma.
abstract: Because of encouraging response rates published with recombinant interleukin-2 (rIL-2) alone in metastatic malignant melanoma (MMM), dacarbazine (DTIC) and rIL-2 were sequentially combined to evaluate efficacy, toxicity, pharmacokinetics, and immunologic interaction. Thirty-two patients aged 18 to 67 years have received 127 courses of treatment. The dose of DTIC was 1.0 g/m2 as a 24-hour infusion every 28 days on day 1. Recombinant interleukin-2 (2.0, 3.0, 4.0, or 5.0 x 10(6) Cetus units/m2) was administered as a 30-minute infusion on days 15 through 19 and 22 through 26 of each 28-day cycle. Seven of 32 patients (22%) who received therapy had a remission, one complete and six partial. The complete response was in a lung mass. Partial responses were seen in lymph nodes, liver, and lung. The median duration of response was 4.7 months. One patient is in persistent partial remission of the liver for greater than 2 years. One patient had residual mediastinal disease resected after partial response and remains without evidence of disease for 18+ months. This regimen was generally well tolerated, did not create overlapping toxicity, and produced encouraging responses in visceral sites. This provides a framework for future combinations of chemotherapy with rIL-2 alone or in combination with other biologic response modifiers in an outpatient setting.
authors.affiliation: Department of Internal Medicine, Harper Hospital, Wayne State University School of Medicine, Detroit, Michigan 48201.
authors.forename: L E
authors.initials: LE
authors.lastname: Flaherty
authors.forename: B G
authors.initials: BG
authors.lastname: Redman
authors.forename: G G
authors.initials: GG
authors.lastname: Chabot
authors.forename: S
authors.initials: S
authors.lastname: Martino
authors.forename: S M
authors.initials: SM
authors.lastname: Gualdoni
authors.forename: L K
authors.initials: LK
authors.lastname: Heilbrun
authors.forename: M
authors.initials: M
authors.lastname: Valdivieso
authors.forename: E C
authors.initials: EC
authors.lastname: Bradley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins; D003606:Dacarbazine