title: Phase 2 study of frontline bortezomib in patients with advanced non-small cell lung cancer.
abstract: BACKGROUND
  Preliminary results indicated that bortezomib (B) (Velcade*) as a single agent may have activity in pretreated NSCLC patients with similar or lesser toxicity compared to chemotherapy. This phase II study was initiated to determine the efficacy of single-agent B in chemonaïve patients with advanced NSCLC. An early tumor assessment (after 6 weeks of therapy) was performed to allow for rapid and appropriate management of non-responding patients.
  
  
  METHODS
  Patients received B (1.5 mg/m2) twice a week for 2 consecutive weeks (days 1, 4, 8, and 11) followed by a 10-day rest period. The primary endpoint was non-progression rate (NPR) after 6 weeks of treatment. Secondary endpoints included response rate, progression-free survival (PFS), overall survival (OS), and safety. Exploratory analyses included FDG-PET response at 6 weeks and circulating tumors cell (CTC) assessment at day 1 of each cycle in a subset of patients.
  
  
  RESULTS
  18 patients were enrolled from 06/06 to 02/07 from 3 French institutions.
  
  
  METHODS
  male/female 15/3; median age 66 (54-79); PS 0/1/2, 3/12/3; pathology: adenocarcinoma 11, squamous cell carcinoma 5, large-cell carcinoma 2; smoking status never/former/current 1/10/7; stage IIIB/IV 2/16. Seventeen patients received B and 16 were assessable (1 early withdrawal and 1 progression at D26). The most frequent toxicity was fatigue (17 patients). Twelve patients (71%) had at least one grade 3 toxicity: 4 haematological, 1 infection, 5 gastro-intestinal toxicity, 9 fatigue, 1 neuropathy. The non-progression rate was 59% [33-82%] at 6 weeks (10/17 patients). No objective response was seen. With a median follow-up of 12.3 months, the median PFS and OS were 2.4 and 9.8 months respectively. Eleven deaths occurred. No PET response was observed, and CTC were detected only in 1 out of 8 patients evaluated.
  
  
  CONCLUSIONS
  Although according to the protocol rules the trial should not be stopped, the lack of any objective response either by CT-scan or PET-CT, along with substantial toxicity, did not argue in favor of the current strategy of B as a single agent in the front-line setting of NSCLC.
authors.affiliation: Département de Médecine, Institut Gustave Roussy, Villejuif, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
authors.forename: David
authors.initials: D
authors.lastname: Planchard
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Veillard
authors.forename: Laurent
authors.initials: L
authors.lastname: Taillade
authors.forename: David
authors.initials: D
authors.lastname: Khayat
authors.forename: Muriel
authors.initials: M
authors.lastname: Ducourtieux
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pignon
authors.forename: Jean
authors.initials: J
authors.lastname: Lumbroso
authors.forename: Carole
authors.initials: C
authors.lastname: Lafontaine
authors.forename: Claire
authors.initials: C
authors.lastname: Mathiot
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D018287:Carcinoma, Large Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D011379:Prognosis; D011719:Pyrazines / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib