Sequential administration of docetaxel followed by maintenance gefitinib, as salvage treatment in patients with advanced NSCLC: a multicenter phase II trial.
ABSTRACT To evaluate the activity and toxicity of the sequential administration of docetaxel followed by gefitinib in patients with advanced non-small cell lung cancer (NSCLC).
Forty-one patients pre-treated with at least one prior chemotherapy regimen (platinum- or taxane-based) for advanced/metastatic NSCLC received three cycles of docetaxel 30 mg/m2, administered as a 1-h IV infusion, on days 1, 8 and 15 of each 4-week cycle followed by gefitinib 250 mg daily po. Gefitinib treatment was continued until disease progression, development of unacceptable toxicity, or withdrawal of patients consent.
Two (4.9%) patients achieved a partial response and 10 (24.4%) stable disease, for a disease control rate of 29.3% (95% CI: 15.3%-43.2%) while on weekly docetaxel treatment. Additionally, progressive disease (PD) was observed in 29 (70.7%). No objective responses were observed during the gefitinib maintenance therapy; however, 17 (41.5%) patients presented stable disease maintained for more than 2 months. Median time to progression was 3.0 months (range: 1-38.3 months; 95% CI: 2.4-3.6); median overall survival 6.9 months (range: 1.2-40.2 months; 95% CI: 5.34-8.52) while the 1-year survival was 28.8%. Therapy was generally well tolerated with diarrhea and rash being the most frequent toxicities.
The sequential administration of docetaxel and gefitinib was well tolerated and moderately active against advanced pre-treated NSCLC.
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ABSTRACT: The very early intuition of Paget about the molecular feature of metastasis has come in the field of therapeutic opportunities only in the last few years with the development of targeted therapy. However, to date the diagnosis of metastases is associated in the majority of cases with the loss of any therapeutic hope. According to present knowledge, metastatic spreading is considered as part of a long process in which tumor cells gain new properties in their cellular function, including invasion and adaptive survival. This gain of function is based on the expression of new molecular markers that may be potential therapeutic targets in blocking tumor dissemination. The epidermal growth factor receptor family comprises four members (ERBB) that are frequently upregulated in advanced tumor stages and have been associated with the metastatic potential of several tumors. ERBB receptor inhibitors are very effective against specific primary tumors and their use is frequently accompanied by toxicity problems, drug resistance and molecular desensitization. However, new studies indicate that ERBB inhibitors may provide a much-needed therapeutic option mainly for patients with metastases. In order to illustrate the potential of ERBB family members as therapeutic targets in blocking metastases we summarize the new molecular evidence and the observations from clinical trials.Current cancer drug targets 03/2009; 9(1):1-18. · 5.13 Impact Factor