Expression profiling and long lasting responses to chemotherapy in metastatic gastric cancer.

Current palliative chemotherapy (CT) regimens achieve clinical benefits in less than 50% of patients treated for metastatic gastric cancers, and long-term survivals are anecdotical. Genetic polymorphisms and differences at the level of transcription in genes involved in biological processes of drug metabolism, DNA repair and drug resistance can explain the observed individual differences in response to drugs, in survival and in different susceptibility to the toxic effects of CT. The possibility to classify patients on the basis of genetic signatures could help in choosing the CT regimen. We present herein an analysis of genetic and expression profiling of three patients affected by metastatic gastric cancer, treated with CT and alive, disease-free, at 66-82 months. Four patients with typical clinical outcome represented the control group. Expression profiling from paraffin-embedded tumor tissues was performed on an ad hoc set of genes involved in drug metabolism and resistance, DNA repair, cell cycle regulation and growth factors signalling. Genetic polymorphism analysis on DNA extracted from peripheral blood was done by pyrosequencing of genetic markers predictive of drug response. Expression analysis in long-term survivors revealed a significant upregulation of PTEN, TP63, GADD45a and MAPK1 genes. We found also an upregulation of CYP1A1, CYP3A4 and ERBB4 genes. EGF was found to be down-regulated in long-term survivors. ERCC1 C8092A polymorphism seems to be associated with survival in our set of patients. The present study shed light on a set of genes, which could have a predictive role in survival of patients with metastatic gastric tumors.

Weekly docetaxel and zoledronic acid every 4 weeks in hormone-refractory prostate cancer patients.

OBJECTIVES: To investigate the safety and efficacy of docetaxel and zoledronic acid in patients with hormone-refractory prostate cancer (HRPC), based on preclinical evidence of synergism between taxanes and bisphosphonates. METHODS: Twenty-five patients with advanced HRPC received weekly docetaxel 30 mg/m2: in 18 patients with symptomatic bone metastases and normal renal function, docetaxel was combined with zoledronic acid, 4 mg i.v. every 4 weeks. Premedication consisted of intravenous dexamethasone before docetaxel. No oral steroids were given. RESULTS: Overall, 12 patients (48%) had a PSA response (reduction of 50% or more compared to baseline). A PSA response was achieved in 8/18 patients (44%) receiving concomitant docetaxel and zoledronic acid, and in 7/12 patients (58%) receiving docetaxel and zoledronic acid as first-line therapy. The weekly schedule of docetaxel resulted in a mean received dose intensity of 26 mg/m2/week, or 87% of the planned dose intensity. Toxicity was mild and as expected for docetaxel. The median time to progression was 7 months, and the median overall survival was 16 months. CONCLUSIONS: Concomitant treatment with docetaxel and zoledronic acid is safe and has encouraging activity in HRPC. The combination should be evaluated in randomised clinical trials.

Paclitaxel, cisplatin, 5-fluorouracil and radiotherapy in the management of advanced squamous cell carcinoma of the head and neck: a phase II trial.

Aim of the present study was to test, activity and toxicity of a rapidly alternating chemoradiation (paclitaxel based) in 31 patients with unresectable, locally advanced or recurrent after surgery, head and neck cancer. Three-year overall survival and progression-free survival were 61.4 and 73.7%, respectively. Main side effects remain a major problem.