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We have evaluated the activity and safety of gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with docetaxel as first-line treatment of women with metastatic breast cancer (MBC). In total, 41 patients with MBC were enrolled in a first-line combination therapy study with oral gefitinib (250 mg day(-1)) and intravenous docetaxel (75 mg m(-2), the first 14 patients; or 100 mg m(-2), the following 27 patients, on day 1 of a 3-week cycle). Out of 41 patients, 38 received at least one cycle of therapy. There were no differences in activity or tolerability between the two docetaxel doses. G3/4 toxicities were neutropenia (49%), diarrhoea (10%), acne-like rash (5%), and anaemia (2%). Complete plus partial responses (CR+PR) were observed in 22 out of 41 patients with a 54% response rate (95% confidence interval (CI) 45-75%). The 22 patients that achieved a response following six cycles of docetaxel plus gefitinib continued gefitinib monotherapy (median duration, 24 weeks; range, 2-108+ weeks). Two patients with PR following combination therapy achieved a CR during gefitinib monotherapy. Complete plus partial responses correlated with oestrogen receptor (ER) status, since they occurred in 19 out of 27 (70%) patients with ER-positive tumours as compared to three out of 14 (21%) patients with ER-negative tumours (P=0.01). [ABSTRACT FROM AUTHOR]

More than 50% of lung cancer cases are diagnosed in patients over the age of 65 years, and about 30% are diagnosed in patients over the age of 70 years. Elderly patients do not tolerate chemotherapy as well as their younger counterparts, mainly because of the higher prevalence of comorbid conditions and organ failure in the elderly. Alternatives to conventional chemotherapy, such as new molecular targeted therapies, are of interest. This review summarizes current approaches and recent advances in the treatment of elderly patients with non-small cell lung cancer and gives a perspective on the future of molecular targeted therapies in this population. Epidermal growth factor receptor inhibitors and vascular endothelial growth factor inhibitors are discussed here, being, in our opinion, among the best candidates for clinical development in this setting. Their potential advantages in elderly patients include better tolerability than conventional chemotherapy. [ABSTRACT FROM AUTHOR]

The effects of synovial conditioned medium (SCM) on DNA, proteoglycan (PG), and protein-collagen synthesis and respective gene expressions, in human articular chondrocytes (AC) and DNA synthesis in synovial fibroblasts (SFb), were studied in monolayer culture. All SCM exhibited concentration-dependent inhibition of [3H]thymidine incorporation in both AC and SFb. In contrast, SCM from three OA patients stimulated [35S]SO4 and [3H]glycine incorporations and the expression (RT-PCR) of aggrecan- and type II collagen-specific mRNAs in AC. The production of agents that inhibit DNA synthesis was blocked by indomethacin and dexamethasone and stimulated by IL-1 beta and TNF-alpha. The inhibitory substances were not produced by heat-inactivated tissue nor cultured SFb or AC and were completely solubles in methanol. It is postulated that synovial tissue secretes lipids, most probably arachidonic acid metabolites. These may counteract growth of an inflammatory synovial pannus by inhibiting SFb proliferation and enhance repair of damaged tissues by stimulating the matrix synthesis. [ABSTRACT FROM AUTHOR]

Erlotinib is a small molecule that selectively inhibits epidermal growth factor receptor (EGFR) tyrosine kinase activity. It demonstrated single-agent activity in patients with non-small cell lung cancer (NSCLC). Single-agent chemotherapy is the standard treatment of advanced NSCLC elderly patients. We report a case of a partial response in a 76-year-old never-smoker female affected by advanced lung adenocarcinoma refractory to first- and second-line chemotherapy. [ABSTRACT FROM AUTHOR]