Phase I Study of Navitoclax (ABT-263), a Novel Bcl-2 Family Inhibitor, in Patients With Small-Cell Lung Cancer and Other Solid Tumors

DOI Web Site 14 Citations
  • D. Ross Camidge
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Leena Gandhi
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Moacyr Ribeiro de Oliveira
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Philip Bonomi
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Divis Khaira
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • David Gandara
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Christine L. Hann
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Elizabeth Litvinovich
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Philip M. Hemken
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Evelyn M. McKeegan
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Caroline Dive
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Sari H. Enschede
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Cathy Nolan
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Todd Busman
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Hao Xiong
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Yi-Lin Chiu
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Andrew P. Krivoshik
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Rod Humerickhouse
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Geoffrey I. Shapiro
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.
  • Charles M. Rudin
    From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Cancer Center, Aurora, CO; Northwest Medical Specialties, Tacoma, WA; Rush University Medical Center, Chicago; Abbott Laboratories, Abbott Park, IL; University of California Davis Cancer Center, Sacramento, CA; Sunterra Oncology Associates, Phoenix, AZ; Johns Hopkins University, Baltimore, MD; and Paterson Institute for Cancer Research, University of Manchester, United Kingdom.

Bibliographic Information

Published
2011-03-01
DOI
  • 10.1200/jco.2010.31.6208
Publisher
American Society of Clinical Oncology (ASCO)

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<jats:sec><jats:title>Purpose</jats:title><jats:p> Resistance to chemotherapy-induced apoptosis represents a major obstacle to cancer control. Overexpression of Bcl-2 is seen in multiple tumor types and targeting Bcl-2 may provide therapeutic benefit. A phase I study of navitoclax, a novel inhibitor of Bcl-2 family proteins, was conducted to evaluate safety, pharmacokinetics, and preliminary efficacy in patients with solid tumors. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> Patients enrolled to intermittent dosing cohorts received navitoclax on day −3, followed by dosing on days 1 to 14 of a 21-day cycle. Patients on continuous dosing received a 1-week lead-in dose of 150 mg followed by continuous daily administration. Blood samples were collected for pharmacokinetic analyses, biomarker analyses, and platelet monitoring. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Forty-seven patients, including 29 with small-cell lung cancer (SCLC) or pulmonary carcinoid, were enrolled between 2007 and 2008, 35 on intermittent and 12 on continuous dosing cohorts. Primary toxicities included diarrhea (40%), nausea (34%), vomiting (36%), and fatigue (34%); most were grade 1 or 2. Dose- and schedule-dependent thrombocytopenia was seen in all patients. One patient with SCLC had a confirmed partial response lasting longer than 2 years, and eight patients with SCLC or carcinoid had stable disease (one remained on study for 13 months). Pro-gastrin releasing peptide (pro-GRP) was identified as a surrogate marker of Bcl-2 amplification and changes correlated with changes in tumor volume. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Navitoclax is safe and well tolerated, with dose-dependent thrombocytopenia as the major adverse effect. Preliminary efficacy data are encouraging in SCLC. Efficacy in SCLC and the utility of pro-GRP as a marker of treatment response will be further evaluated in phase II studies. </jats:p></jats:sec>

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