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

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/m(2)) 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.

• Authors: Steven F Powell, Amer Beitinjaneh, Mathewos Tessema, Robin L Bliss, Robert A Kratzke, Joseph Leach, Arkadiusz Z Dudek
• Journal: Clinical lung cancer (Clin Lung Cancer) Vol. 14 Issue 5 Pg. 495-501 (Sep 2013) ISSN: 1938-0690 [Electronic] United States
• PMID: 23816875 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Bevacizumab
• Topotecan

Topics

• Adenocarcinoma (drug therapy, mortality, pathology)
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab
• Carcinoma, Large Cell (drug therapy, mortality, pathology)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality, pathology)
• Cohort Studies
• Drug Resistance, Neoplasm (drug effects)
• Female
• Follow-Up Studies
• Humans
• Lung Neoplasms (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Salvage Therapy
• Survival Rate
• Topotecan (administration & dosage)