Phase II study of topotecan and bevacizumab in advanced, refractory non-small-cell lung cancer

Steven F. Powell, Amer Beitinjaneh, Mathewos Tessema, Robin L. Bliss, Robert A. Kratzke, Joseph Leach, Arkadiusz Z. Dudek

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: This clinical trial evaluated whether topotecan in combination with bevacizumab improved progression-free survival (PFS) in patients with advanced, refractory non-small-cell lung cancer in a second-line setting. Patient and Methods: Patients aged 18 years old and older received topotecan (4.0 mg/m2) on days 1, 8, and 15, and bevacizumab (10 mg/kg) on days 1 and 15 as intravenous infusions on a 28-day treatment cycle. Available tumor specimens were analyzed for ISG15 gene expression as a biomarker of response to topotecan. Results: Forty-two patients were enrolled in the study, with a median age of 62.5 years and a median of 3 (range, 1-7) prior treatment regimens. Almost half (n = 18, 42.9%) of the patients received prior bevacizumab therapy. PFS was 5.1 months (95% CI, 3.7-7.8 months), and overall survival was 11.5 months (95% CI, 6.8-15.5 months). Response rates were as follows: 14.3% partial response, 54.8% stable disease, and 28.6% progressive disease. Hematologic toxicities included grade 3 thrombocytopenia (n = 7, 16.7%), neutropenia (n = 4, 9.5%), and anemia (n = 2, 4.8%). One toxic death occurred due to pulmonary hemorrhage, and one patient experienced a grade 4 pulmonary embolism. Grade 3 nonhematologic adverse events were uncommon (< 8%). There was a trend for improved median PFS, 3.5 months vs. 1.8 months (P =.26), in patients with high ISG15 expression. Conclusion: Bevacizumab in combination with topotecan as a salvage therapy for metastatic non-small-cell lung cancer is well tolerated and is worthy of further investigation.

Original languageEnglish (US)
Pages (from-to)495-501
Number of pages7
JournalClinical Lung Cancer
Volume14
Issue number5
DOIs
StatePublished - Sep 2013
Externally publishedYes

Keywords

  • Bevacizumab
  • ISG15 expression
  • Non-small-cell lung cancer
  • Refractory
  • Second-line therapy
  • Topotecan

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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