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.
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: Kathryn F McGonigle; Howard G Muntz; Jacqueline Vuky; Pamela J Paley; Dan S Veljovich; Benjamin E Greer; Barbara A Goff; Heidi J Gray; Thomas W Malpass Journal: Cancer Date: 2011-02-24 Impact factor: 6.860
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Authors: G Fontanini; M Lucchi; S Vignati; A Mussi; F Ciardiello; M De Laurentiis; S De Placido; F Basolo; C A Angeletti; G Bevilacqua Journal: J Natl Cancer Inst Date: 1997-06-18 Impact factor: 13.506
Authors: Alan Sandler; Robert Gray; Michael C Perry; Julie Brahmer; Joan H Schiller; Afshin Dowlati; Rogerio Lilenbaum; David H Johnson Journal: N Engl J Med Date: 2006-12-14 Impact factor: 91.245
Authors: Nasser Hanna; Frances A Shepherd; Frank V Fossella; Jose R Pereira; Filippo De Marinis; Joachim von Pawel; Ulrich Gatzemeier; Thomas Chang Yao Tsao; Miklos Pless; Thomas Muller; Hong-Liang Lim; Christopher Desch; Klara Szondy; Radj Gervais; Christian Manegold; Sofia Paul; Paolo Paoletti; Lawrence Einhorn; Paul A Bunn Journal: J Clin Oncol Date: 2004-05-01 Impact factor: 44.544
Authors: M Tessema; C M Yingling; C L Thomas; D M Klinge; A M Bernauer; Y Liu; S Dacic; J M Siegfried; S E Dahlberg; J H Schiller; S A Belinsky Journal: Oncogene Date: 2011-12-12 Impact factor: 9.867