Phase II study of vandetanib or placebo in small-cell lung cancer patients after complete or partial response to induction chemotherapy with or without radiation therapy: National Cancer Institute of Canada Clinical Trials Group Study BR.20 - PubMed (original) (raw)
Clinical Trial
. 2007 Sep 20;25(27):4278-84.
doi: 10.1200/JCO.2007.12.3083.
Lesley Seymour, Michael Smylie, Keyue Ding, Yee Ung, Brian Findlay, Christopher W Lee, Marina Djurfeldt, Marlo Whitehead, Peter Ellis, Glenwood Goss, Adrien Chan, Jacinta Meharchand, Yasmin Alam, Richard Gregg, Charles Butts, Peter Langmuir, Frances Shepherd; National Cancer Institute of Canada Clinical Trials Group Study BR.20
Affiliations
- PMID: 17878480
- DOI: 10.1200/JCO.2007.12.3083
Clinical Trial
Phase II study of vandetanib or placebo in small-cell lung cancer patients after complete or partial response to induction chemotherapy with or without radiation therapy: National Cancer Institute of Canada Clinical Trials Group Study BR.20
Andrew M Arnold et al. J Clin Oncol. 2007.
Abstract
Purpose: This double-blind randomized phase II trial examined whether vandetanib, an inhibitor of vascular endothelial and epidermal growth factor receptors, could prolong progression-free survival in responding patients with small-cell lung cancer.
Patients and methods: Eligible patients with complete response (CR) or partial response (PR) to combination chemotherapy (+/- thoracic or prophylactic cranial radiation) received oral vandetanib 300 mg/d or matched placebo. With 100 patients and 77 events, the study had 80% power to detect an improvement in median progression-free survival from 4 to 6.5 months (one-sided, 10%-level test).
Results: Between May 2003 and March 2006, 107 patients were accrued; 46 had limited disease and 61 extensive disease. There were fewer patients with a performance status of 0 (n = 11 v 20), and fewer had CR to initial therapy (n = 4 v 8) in the vandetanib arm. Vandetanib patients had more toxicity and required more dose modifications for gastrointestinal toxicity and rash. Asymptomatic Corrected QT interval (QTC) prolongation was observed in eight vandetanib patients. Median progression-free survival for vandetanib and placebo was 2.7 and 2.8 months, respectively (hazard ratio [HR], 1.01; 80% CI, 0.75 to 1.36; one-sided P = .51). Overall survival for vandetanib was 10.6 versus 11.9 months for placebo (HR, 1.43; 80% CI, 1.00 to 2.05; one-sided P = 0.9). In planned subgroup analyses, a significant interaction was noted (P = .01): limited-stage vandetanib patients had longer overall survival (HR, 0.45; one-sided P = .07) and extensive-stage vandetanib patients shorter survival compared with placebo (HR, 2.27; one-sided P = .996).
Conclusion: Vandetanib failed to demonstrate efficacy as maintenance therapy for small-cell lung cancer.
Comment in
- The debate about maintenance is not over in small-cell lung cancer.
Artac M, Bozcuk H. Artac M, et al. J Clin Oncol. 2007 Dec 20;25(36):5840; author reply 5840-1. doi: 10.1200/JCO.2007.14.6183. J Clin Oncol. 2007. PMID: 18089887 No abstract available.
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