title: Bortezomib plus docetaxel in advanced non-small cell lung cancer and other solid tumors: a phase I California Cancer Consortium trial.
abstract: BACKGROUND
  This phase I study was performed to determine the dose-limiting toxicity and maximum tolerated dose (MTD) of docetaxel in combination with bortezomib in patients with advanced non-small cell lung cancer (NSCLC) or other solid tumors.
  
  
  METHODS
  Patients were enrolled in cohorts of three over six dose levels. Each treatment cycle was 3 weeks long and consisted of one docetaxel infusion (day 1) and four bortezomib injections (days 1, 4, 8, and 11). Dose escalation and MTD determination were based on the occurrence of dose-limiting toxicities in cycle 1 only.
  
  
  RESULTS
  A total of 36 patients were enrolled, 26 of whom had NSCLC. All patients received at least one dose of study drug at one of five dose levels. The MTD of the combined regimen was determined to be 1.0/75 mg/m bortezomib/docetaxel. The combination was generally well tolerated. Toxicities were manageable, and no additive toxicities were observed. The most common adverse events were fatigue (67% of patients), nausea (50%), diarrhea (39%), and neutropenia (39%). Two patients with NSCLC achieved a partial response, and seven (19%) patients achieved stable disease (including six patients with NSCLC).
  
  
  CONCLUSIONS
  The combination of bortezomib and docetaxel was feasible and well tolerated in patients with advanced NSCLC or other solid tumors. The recommended phase II dose is bortezomib 1.0 mg/m on days 1, 4, 8, and 11 plus docetaxel 75 mg/m on day 1, cycled every 21 days. Therapeutic doses of docetaxel and bortezomib are achievable for this combination.
authors.affiliation: University of California, Davis Cancer Center, Sacramento, California 95817, USA. Primo.Lara@ucdmc.ucdavis.edu
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: Mariana
authors.initials: M
authors.lastname: Koczywas
authors.forename: David I
authors.initials: DI
authors.lastname: Quinn
authors.forename: Heinz Josef
authors.initials: HJ
authors.lastname: Lenz
authors.forename: Angela M
authors.initials: AM
authors.lastname: Davies
authors.forename: Derick H M
authors.initials: DH
authors.lastname: Lau
authors.forename: Paul H
authors.initials: PH
authors.lastname: Gumerlock
authors.forename: Jeff
authors.initials: J
authors.lastname: Longmate
authors.forename: James H
authors.initials: JH
authors.lastname: Doroshow
authors.forename: David
authors.initials: D
authors.lastname: Schenkein
authors.forename: Oscar
authors.initials: O
authors.lastname: Kashala
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D000069286:Bortezomib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents; D015996:Survival Rate / Q000639:trends; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; D000069286:Bortezomib