title: Low-dose cyclophosphamide and low-dose interleukin-2 for malignant melanoma.
abstract: We have studied the effects of low-dose recombinant interleukin-2 preceded by low-dose cyclophosphamide on malignant melanoma. Thirty eight outpatients aged from 25 to 75 years were treated with interleukin-2, 3.6 million Cetus units/m2 i.v. daily for five days on two successive weeks beginning three days after 350 mg/m2 of intravenous cyclophosphamide. This schedule was repeated at least twice more with a one-week interval between cycles, usually at the same dosage level. Ten of the 38 patients (26.3%) had clinically significant remissions: two complete (5.3%), seven partial (18.4%), and one ongoing, long-term (greater than 18 mo) "minor" response (2.6%). Four others (10.5%) had shorter minor responses and four (10.5%) a mixed response. One patient with disease restricted to the skin had a complete remission, while the other patient with a complete remission had had three lung nodules and an enlarged hilar lymph node. It was gratifying that one of the major sites of disease responding to treatment was the liver. Two complete and two partial remissions (i.e., greater than 50% regressions for greater than four weeks at this site) were obtained in 10 patients with liver involvement. Lung metastases also responded in four of 16 patients (one complete and three partial remissions). Subcutaneous nodules responded in seven of 21 patients (two complete, five partial remissions), while lymph node metastases diminished significantly in four of 14 patients (one complete, three partial remissions). The median duration of response was nine months (range, 1.5-20 months), with four patients treated for more than one year. Toxicity was moderate and controllable, and only two patients required hospitalization, both overnight. Lymphokine activated killer cell activation was induced in 24 of 38 patients, including all nine of the major responders. Conversely, none of 14 patients without lymphokine activated killer cell activation had a significant clinical remission. This regimen appeared to be as effective in melanoma as those involving ex vivo activation of lymphokine activated killer cells, and was more tolerable than therapy with high doses of interleukin-2.
authors.forename: M S
authors.initials: MS
authors.lastname: Mitchell
authors.forename: R A
authors.initials: RA
authors.lastname: Kempf
authors.forename: W
authors.initials: W
authors.lastname: Harel
authors.forename: H
authors.initials: H
authors.lastname: Shau
authors.forename: W D
authors.initials: WD
authors.lastname: Boswell
authors.forename: S
authors.initials: S
authors.lastname: Lind
authors.forename: G
authors.initials: G
authors.lastname: Dean
authors.forename: J
authors.initials: J
authors.lastname: Moore
authors.forename: E C
authors.initials: EC
authors.lastname: Bradley
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D015166:Monitoring, Immunologic; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D007376:Interleukin-2; D003520:Cyclophosphamide; D007213:Indomethacin