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). CONCLUSION: 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.
RCT Entities:
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). CONCLUSION: 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: Primo N Lara; Jeff Longmate; Karen Reckamp; Barbara Gitlitz; Athanassios Argiris; Suresh Ramalingam; Chandra P Belani; Philip C Mack; Derick H M Lau; Mariana Koczywas; John J Wright; Frances A Shepherd; Natasha Leighl; David R Gandara Journal: Clin Lung Cancer Date: 2011-01 Impact factor: 4.785
Authors: Gregory J Kubicek; Maria Werner-Wasik; Mitchell Machtay; Gayle Mallon; Thomas Myers; Michael Ramirez; David Andrews; Walter J Curran; Adam P Dicker Journal: Int J Radiat Oncol Biol Phys Date: 2008-12-10 Impact factor: 7.038
Authors: Amanda F Baker; Neale T Hanke; Barbara J Sands; Liliana Carbajal; Janet L Anderl; Linda L Garland Journal: J Exp Clin Cancer Res Date: 2014-12-31
Authors: A Z Dudek; K Lesniewski-Kmak; N J Shehadeh; O N Pandey; M Franklin; R A Kratzke; E W Greeno; P Kumar Journal: Br J Cancer Date: 2009-05-05 Impact factor: 7.640
Authors: A Awada; J Albanell; P A Canney; L Y Dirix; T Gil; F Cardoso; P Gascon; M J Piccart; J Baselga Journal: Br J Cancer Date: 2008-04-29 Impact factor: 7.640