Bortezomib (PS-341) in relapsed or refractory extensive stage small cell lung cancer: A Southwest Oncology Group phase II trial (S0327)

Primo N Lara, Kari Chansky, Angela M. Davies, Wilbur A. Franklin, Paul H. Gumerlock, Perry P. Guaglianone, James N. Atkins, Nichole Farneth, Philip Mack, John J. Crowley, David R Gandara

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

BACKGROUND: In preclinical models, the proteasome inhibitor bortezomib (PS-341) inhibits the growth of small cell lung cancer (SCLC) by inhibiting the antiapoptotic Bcl-2 signaling pathway. We conducted a phase II trial of PS-341 in previously treated patients with platinum-sensitive and -refractory extensive stage SCLC to determine response rate, toxicity, and survival. METHODS: Patients with histologically confirmed SCLC, measurable disease, Zubrod performance status 0-1, and previous treatment with platinum-based therapy were enrolled. They were stratified by platinum-sensitivity status: sensitive (relapse >90 days after platinum) or refractory (progression during or ≤90 days after platinum). PS-341 was administered at 1.3 mg/m intravenously on days 1, 4, 8, and 11 every 21 days. RESULTS: Of 56 eligible patients, 28 were platinum sensitive and 28 refractory. Twenty-nine patients (52%) had received two or more previous chemotherapy regimens. One platinum-refractory patient had a confirmed partial response. A majority of assessable patients (91%) progressed. Median progression-free survival and overall survival were 1 month and 3 months, respectively. Ten patients (18%) discontinued treatment due to adverse events or side effects. CONCLUSION: Although PS-341 induced a response in a patient with platinum-refractory disease, it has limited single-agent activity in this heavily pretreated cohort. As shown in preclinical models, testing of PS-341 in combination with an apoptotic trigger such as chemotherapy, is a rational clinical approach. A trial of topotecan plus PS-341 has been initiated to test this concept.

Original languageEnglish (US)
Pages (from-to)996-1001
Number of pages6
JournalJournal of Thoracic Oncology
Volume1
Issue number9
DOIs
StatePublished - Nov 2006

Keywords

  • Bcl-2
  • Bortezomib
  • Proteasome inhibition
  • Small cell lung cancer

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Bortezomib (PS-341) in relapsed or refractory extensive stage small cell lung cancer: A Southwest Oncology Group phase II trial (S0327)'. Together they form a unique fingerprint.

  • Cite this