title: A randomized, multicenter study to determine the safety and efficacy of the immunoconjugate SGN-15 plus docetaxel for the treatment of non-small cell lung carcinoma.
abstract: OBJECTIVE
  Chemotherapy prolongs survival and improves quality of life (QOL) for good performance status (PS) patients with advanced non-small cell lung cancer (NSCLC). Targeted therapies may improve chemotherapy effectiveness without worsening toxicity. SGN-15 is an antibody-drug conjugate (ADC), consisting of a chimeric murine monoclonal antibody recognizing the Lewis Y (Le(y)) antigen, conjugated to doxorubicin. Le(y) is an attractive target since it is expressed by most NSCLC. SGN-15 was active against Le(y)-positive tumors in early phase clinical trials and was synergistic with docetaxel in preclinical experiments. This Phase II, open-label study was conducted to confirm the activity of SGN-15 plus docetaxel in previously treated NSCLC patients.
  
  
  METHODS
  Sixty-two patients with recurrent or metastatic NSCLC expressing Le(y), one or two prior chemotherapy regimens, and PS< or =2 were randomized 2:1 to receive SGN-15 200 mg/m2/week with docetaxel 35 mg/m2/week (Arm A) or docetaxel 35 mg/m2/week alone (Arm B) for 6 of 8 weeks. Intrapatient dose-escalation of SGN-15 to 350 mg/m2 was permitted in the second half of the study. Endpoints were survival, safety, efficacy, and quality of life.
  
  
  RESULTS
  Forty patients on Arm A and 19 on Arm B received at least one treatment. Patients on Arms A and B had median survivals of 31.4 and 25.3 weeks, 12-month survivals of 29% and 24%, and 18-month survivals of 18% and 8%, respectively. Toxicity was mild in both arms. QOL analyses favored Arm A.
  
  
  CONCLUSIONS
  SGN-15 plus docetaxel is a well-tolerated and active second and third line treatment for NSCLC patients. Ongoing studies are exploring alternate schedules to maximize synergy between these agents.
authors.affiliation: Thoracic Oncology Program, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, 4805 NE Glisan Street, #5F40 Portland, OR 97213, United States. hross@orclinic.com
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Ross
authors.forename: Lowell L
authors.initials: LL
authors.lastname: Hart
authors.forename: Paul M
authors.initials: PM
authors.lastname: Swanson
authors.forename: Mark U
authors.initials: MU
authors.lastname: Rarick
authors.forename: Robert A
authors.initials: RA
authors.lastname: Figlin
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Jacobs
authors.forename: David E
authors.initials: DE
authors.lastname: McCune
authors.forename: Arthur H
authors.initials: AH
authors.lastname: Rosenberg
authors.forename: Ari D
authors.initials: AD
authors.lastname: Baron
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Grove
authors.forename: Michael D
authors.initials: MD
authors.lastname: Thorn
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Miller
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Drachman
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011788:Quality of Life; D015996:Survival Rate; D043823:Taxoids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States
chemical_list: D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D018796:Immunoconjugates; D043823:Taxoids; D000077143:Docetaxel