Bortezomib plus docetaxel in advanced non-small cell lung cancer and other solid tumors

A phase I california cancer consortium trial

Primo N Lara, Mariana Koczywas, David I. Quinn, Heinz Josef Lenz, Angela M. Davies, Derick H Lau, Paul H. Gumerlock, Jeff Longmate, James H. Doroshow, David Schenkein, Oscar Kashala, David R Gandara

Research output: Contribution to journalArticle

28 Citations (Scopus)

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). 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 75mg/m on day 1, cycled every 21 days. Therapeutic doses of docetaxel and bortezomib are achievable for this combination.

Original languageEnglish (US)
Pages (from-to)126-134
Number of pages9
JournalJournal of Thoracic Oncology
Volume1
Issue number2
DOIs
StatePublished - Feb 2006

Fingerprint

docetaxel
Non-Small Cell Lung Carcinoma
Neoplasms
Maximum Tolerated Dose
Bortezomib
Neutropenia

Keywords

  • Bortezomib
  • Docetaxel
  • Non-small cell lung cancer
  • Proteasome

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Medicine(all)

Cite this

Bortezomib plus docetaxel in advanced non-small cell lung cancer and other solid tumors : A phase I california cancer consortium trial. / Lara, Primo N; Koczywas, Mariana; Quinn, David I.; Lenz, Heinz Josef; Davies, Angela M.; Lau, Derick H; Gumerlock, Paul H.; Longmate, Jeff; Doroshow, James H.; Schenkein, David; Kashala, Oscar; Gandara, David R.

In: Journal of Thoracic Oncology, Vol. 1, No. 2, 02.2006, p. 126-134.

Research output: Contribution to journalArticle

Lara, Primo N ; Koczywas, Mariana ; Quinn, David I. ; Lenz, Heinz Josef ; Davies, Angela M. ; Lau, Derick H ; Gumerlock, Paul H. ; Longmate, Jeff ; Doroshow, James H. ; Schenkein, David ; Kashala, Oscar ; Gandara, David R. / Bortezomib plus docetaxel in advanced non-small cell lung cancer and other solid tumors : A phase I california cancer consortium trial. In: Journal of Thoracic Oncology. 2006 ; Vol. 1, No. 2. pp. 126-134.
@article{456391eb48524020b5045ae4488852f0,
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). 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 75mg/m on day 1, cycled every 21 days. Therapeutic doses of docetaxel and bortezomib are achievable for this combination.",
keywords = "Bortezomib, Docetaxel, Non-small cell lung cancer, Proteasome",
author = "Lara, {Primo N} and Mariana Koczywas and Quinn, {David I.} and Lenz, {Heinz Josef} and Davies, {Angela M.} and Lau, {Derick H} and Gumerlock, {Paul H.} and Jeff Longmate and Doroshow, {James H.} and David Schenkein and Oscar Kashala and Gandara, {David R}",
year = "2006",
month = "2",
doi = "10.1097/01243894-200602000-00005",
language = "English (US)",
volume = "1",
pages = "126--134",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "2",

}

TY - JOUR

T1 - Bortezomib plus docetaxel in advanced non-small cell lung cancer and other solid tumors

T2 - A phase I california cancer consortium trial

AU - Lara, Primo N

AU - Koczywas, Mariana

AU - Quinn, David I.

AU - Lenz, Heinz Josef

AU - Davies, Angela M.

AU - Lau, Derick H

AU - Gumerlock, Paul H.

AU - Longmate, Jeff

AU - Doroshow, James H.

AU - Schenkein, David

AU - Kashala, Oscar

AU - Gandara, David R

PY - 2006/2

Y1 - 2006/2

N2 - 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 75mg/m on day 1, cycled every 21 days. Therapeutic doses of docetaxel and bortezomib are achievable for this combination.

AB - 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 75mg/m on day 1, cycled every 21 days. Therapeutic doses of docetaxel and bortezomib are achievable for this combination.

KW - Bortezomib

KW - Docetaxel

KW - Non-small cell lung cancer

KW - Proteasome

UR - http://www.scopus.com/inward/record.url?scp=34247882671&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247882671&partnerID=8YFLogxK

U2 - 10.1097/01243894-200602000-00005

DO - 10.1097/01243894-200602000-00005

M3 - Article

VL - 1

SP - 126

EP - 134

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

IS - 2

ER -