title: Phase I trial of murine monoclonal antibody L6 in combination with subcutaneous interleukin-2 in patients with advanced carcinoma of the breast, colorectum, and lung.
abstract: OBJECTIVE
  A phase I trial was undertaken to determine the toxicity and biologic effects of a combination of murine monoclonal antibody L6 (MoAb L6) plus subcutaneous (SC) interleukin-2 (IL-2).
  
  
  METHODS
  Fifteen patients with refractory adenocarcinoma (five breast, five lung, five colorectal), received L6 at 200 mg/m2 intravenously (IV) daily on days 1 to 7, followed by a 1-week rest period. IL-2 was given at either 2, 3, or 4.5 x 10(6) U/m2 daily doses times 4 days for a total duration of 3 weeks.
  
  
  RESULTS
  Side effects of L6 consisted of mild fever and chills along with a rash and serum sickness in one patient. One patient developed dyspnea and urticaria, that resolved with antihistamines. Maximum-tolerated dose (MTD) of SC IL-2 was 3 x 10(6) U/m2, with dose-limiting toxicities that consisted of grade 4 fatigue and dyspnea. Significant decreases in complement levels along with increases in absolute lymphocyte count and eosinophil count were observed. Mean antibody-dependent cellular cytotoxicity from mononuclear cells taken from patients who received IL-2 was elevated significantly compared with baseline in all patients independent of IL-2 dose (P less than .05). Serum IL-2 levels were elevated in 13 of 14 patients (range, 0.9 to 100 U/mL). Human antimouse antibody (HAMA) titers were elevated in nine of 14 (64%) patients who were tested between 3 and 8 weeks after L6 infusion. One patient with breast cancer had a transient mixed response, and one patient with colorectal cancer had a partial response.
  
  
  CONCLUSIONS
  L6 and SC IL-2 were well tolerated in the majority of patients when given in the outpatient setting. In view of the clinical efficacy of this combination, more phase II trials are warranted.
authors.affiliation: Department of Clinical Immunology and Biological Therapy, University of Texas MD Anderson Cancer Center, Houston 77030.
authors.forename: L D
authors.initials: LD
authors.lastname: Ziegler
authors.forename: P
authors.initials: P
authors.lastname: Palazzolo
authors.forename: J
authors.initials: J
authors.lastname: Cunningham
authors.forename: M
authors.initials: M
authors.lastname: Janus
authors.forename: K
authors.initials: K
authors.lastname: Itoh
authors.forename: K
authors.initials: K
authors.lastname: Hayakawa
authors.forename: I
authors.initials: I
authors.lastname: Hellstrom
authors.forename: K E
authors.initials: KE
authors.lastname: Hellstrom
authors.forename: C
authors.initials: C
authors.lastname: Nicaise
authors.forename: R
authors.initials: R
authors.lastname: Dennin
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000097:blood; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D007376:Interleukin-2