title: A phase II, open-label trial of bortezomib (VELCADE(®)) in combination with gemcitabine and cisplatin in patients with locally advanced or metastatic non-small cell lung cancer.
abstract: Bortezomib is a selective reversible proteasome inhibitor with proapoptotic effects. Preclinical and phase I clinical data suggest activity of bortezomib in NSCLC, either as monotherapy or in combination with chemotherapeutic agents including gemcitabine and cisplatin.
  
  
  
  Chemotherapy-naïve patients with inoperable stage IIIB or IV NSCLC were administered bortezomib 1 mg/m(2) i.v. on days 1 and 8, and starting on day 21 (cycle 2), bortezomib (days 1 and 8) in combination with gemcitabine 1000 mg/m(2), (days 1 and 8), and cisplatin 70 mg/m(2) (day 1) in cycles of 21 days. Up to 8 cycles of combination therapy could be administered; single-agent bortezomib was continued until disease progression or unacceptable toxicity.
  
  
  
  Fifty-three patients [median age 66 years; 79.2 % male; 96.2 % stage IV; performance status (ECOG) 0/1 73.6/26.4 %; adenocarcinoma 45.3 %, squamous cell carcinoma 41.5 %] were enrolled. All patients were evaluable for toxicity and 43 for efficacy. Grade 3-4 hematologic toxicity consisted of neutropenia (22.6 %) and thrombocytopenia (17 %). Grade 2-4 non-hematologic adverse events were fever (9.4 %), fatigue (20.8 %), infection (18.9 %), and dyspnea (15.1 %). There was no >grade 2 neurotoxicity. Febrile neutropenia occurred in two (1.9 %) patients, and there were three possibly treatment-related deaths (5.4 %). In the intention-to-treat population, the objective response rate was 17 % (95 % CI 6.9-27.1 %). No difference in response rate was observed for squamous versus other histology (18.2 vs. 16.1 %, p = 0.845). The median progression-free survival was 2.5 months, the median overall survival 10.6 months and the 1-year survival rate 38.1 %.
  
  
  
  The incorporation of bortezomib into the gemcitabine/cisplatin regimen, in the dose and schedule used in this study, could not improve the efficacy of the chemotherapy regimen and has not to be further investigated.
authors.affiliation: Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Kontopodis
authors.affiliation: Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Kotsakis
authors.affiliation: Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Kentepozidis
authors.affiliation: Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Syrigos
authors.affiliation: Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Ziras
authors.affiliation: Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Moutsos
authors.affiliation: Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Filippa
authors.affiliation: Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Mala
authors.affiliation: Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors.forename: L
authors.initials: L
authors.lastname: Vamvakas
authors.affiliation: Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Mavroudis
authors.affiliation: Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece. info@horg.gr.
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.affiliation: Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Agelaki
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000069286:Bortezomib; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Bortezomib; Cisplatin; Gemcitabine; Non-small cell lung cancer