title: Bortezomib for patients with advanced-stage bronchioloalveolar carcinoma: a California Cancer Consortium Phase II study (NCI 7003).
abstract: BACKGROUND
  Bronchioloalveolar carcinoma (BAC), a subtype of non-small cell lung cancer, is a difficult disease to treat with low response rates with cytotoxic chemotherapy. Bortezomib, a proteasome inhibitor, has demonstrated objective responses in patients with BAC in early-phase clinical trials. We conducted a phase II study of bortezomib in patients with advanced-stage BAC.
  
  
  METHODS
  Patients with advanced BAC, adenocarcinoma with BAC features or BAC with adenocarcinoma features, and less than two prior regimens were eligible. Prior epidermal growth factor receptor (EGFR) inhibitor therapy was allowed. Bortezomib was administered intravenously at 1.6 mg/m on days 1 and 8 of every 21-day cycle until disease progression or unacceptable toxicity. The primary end point was response rate. The Simon two-stage design was used.
  
  
  RESULTS
  Forty-two patients were enrolled, and the study was halted early for slow accrual. Patient characteristics were female 55%, median age 68 years, and Eastern Cooperative Oncology Group performance status of 0 and 1 in 31 and 11 patients, respectively. Twenty-six (62%) patients had received prior therapy with an EGFR inhibitor. A median of four cycles of therapy were administered. Objective responses were noted in 5%, whereas 57% had disease stabilization. The median progression-free survival and overall survival were 5.5 and 13.6 months, respectively. Grade 3 diarrhea and fatigue were noted in three and five patients, respectively.
  
  
  CONCLUSIONS
  Bortezomib is tolerated well and is associated with modest anticancer activity in patients with advanced BAC, including patients who progressed on EGFR inhibitor therapy.
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA. suresh.ramalingam@emory.edu
authors.forename: Suresh S
authors.initials: SS
authors.lastname: Ramalingam
authors.forename: Angela M
authors.initials: AM
authors.lastname: Davies
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Longmate
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Miguel
authors.initials: M
authors.lastname: Villalona-Calero
authors.forename: Barbara
authors.initials: B
authors.lastname: Gitlitz
authors.forename: Karen
authors.initials: K
authors.lastname: Reckamp
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
authors.forename: John J
authors.initials: JJ
authors.lastname: Wright
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy*; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002140:California; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib