Expression profile as predictor of relapse after adjuvant treatment in gastric cancer.

INTRODUCTION: TNM and histological subtype are the most important prognostic criteria in gastric cancer. In this study, we have tried to identify an immunohistochemical protein profile involved in gastric recurrence after a radical surgery. MATERIALS AND METHODS: In this paper, protein panels involved in gastric carcinogenesis and progression was analyzed by immunohistochemistry expression: p53, Ki-67, Bcl-2, COX-2, c-erb-B2, EPO-R, E-cadherin, and ß-catenin in 44 gastrectomy samples coming from gastrectomy pieces of patients diagnosed and operated on adenocarcinoma of the stomach followed by adjuvant treatment based on MacDonald chemoradiation regimen. An immunostaining profile that could predict the relapse after the end of adjuvant treatment was tried to find. These results have shown that the expression of the adverse prognostic protein profile based on positive p53 immunohistochemical expression and non-conserved E-cadherin/B-catenin staining is associated with tumor recurrence and a poor disease-free survival in operated gastric cancer patients with curative intent followed by adjuvant chemoradiation according to MacDonald's regimen. A protein profile based on immunohistochemical expression of p53 and E-cadherin-B-catenin that has a significant correlation to disease-free survival was identified in gastric cancer samples.

Role of anti-Her-2 therapy in bladder carcinoma.

Bladder cancer, in its advanced stage, has very few therapeutic strategies with proven efficacy. Platinum-combination chemotherapy can be considered a standard for first-line therapy, but after progression there is no standard therapy, and the prognosis is very poor. The development of targeted therapies in the last few years has significantly changed the prognosis of a wide variety of tumors. In bladder cancer, there is no targeted therapy currently approved for its use in advanced disease. There is evidence that Her-2 amplification and/or overexpression is seen in bladder cancer, and may influence prognosis. Anti-Her-2 drugs, such as trastuzumab or lapatinib, are under investigation in urothelial neoplasms, but there is no phase III trial that has evaluated their use in bladder cancer. We review the published evidence about Her-2 determination, its influence on bladder carcinoma prognosis, the clinical development of anti-Her-2-targeted therapies, and the possible future research directions involving this pathway in bladder cancer.

Adjuvant chemotherapy for breast cancer and cognitive impairment.

Complaints of loss of memory and lack of concentration have been reported by long-term survivors of breast cancer. This mild cognitive impairment (MCI), also called "chemobrain" or "chemofog," has been the subject of a number of studies in the last few years. This cognitive impairment, although usually mild, must be studied to define possible risk factors for its development, and for future research into a preventive or therapeutic treatment approach. Long-term survivors of breast cancer must be followed to detect possible treatment sequelae as soon as possible. Since the number of these long-term survivors has increased in the last years, in part because of more active adjuvant treatments, our knowledge about the long-term side effects of these therapies has also grown.

Complete and rapid response to FOLFIRI plus bevacizumab in a patient presenting with impaired liver function and poor performance status from colon cancer liver metastases.

Impaired liver function is a final complication of hepatic metastases from colon cancer. This disease status is of critical importance at first clinical presentation because of the tight therapeutic window for chemotherapy. A rapid response to treatment is required as other means of supportive care for hepatic function are limited. New targeted therapies including monoclonal antibodies directed against several proteins with key roles in colon cancer biology are now available, allowing new treatment options for this group of patients. Here, we present a patient with highly impaired liver function secondary to hepatic metastases from colon cancer that showed clinical and radiological improvement after systemic treatment including bevacizumab.

Bevacizumab: a safe and effective treatment in a patient with advanced colorectal cancer and repeated removal of metastases.

Bevacizumab has been shown to be effective combined with chemotherapy for first-line treatment of advanced colorectal cancer, but little information is available about its efficacy and safety in patients who may be candidates for surgery at any time during the disease. The case history of a female patient with colorectal cancer, undergoing surgery for liver metastases and bilateral surgery for lung metastases at different time-points during her disease, is reported. Perioperative bevacizumab administration caused no complications either associated with surgery, in the early postoperative period, or in the subsequent months.

Early intervention with epoetin beta prevents severe anaemia in lung cancer patients receiving platinum-based chemotherapy: a subgroup analysis of the NeoPrevent study.

The NeoPrevent study showed that early intervention with epoetin beta could prevent severe anaemia in patients with solid tumours receiving platinum-based chemotherapy. An early intervention strategy may be particularly warranted in patients with lung cancer, as anaemia is very common in these patients and can be severe. The purpose of this study was to examine the efficacy and safety of epoetin beta in the subpopulation of patients with lung cancer included in the NeoPrevent study. Patients were enrolled if baseline haemoglobin (Hb) levels were 1g/dl) plus the proportion whose Hb was maintained at +/-1g/dl of baseline. Quality of life (QoL) was measured using the linear analogue scale assessment. The NeoPrevent study included 255 patients in total, and the results for the 102 patients with lung cancer (non-small-cell lung cancer 64%; small-cell lung cancer 36%) are presented here. The overall anaemia prevention response was 90%, with Hb response in 60% of patients and maintenance of baseline Hb level in 30%. Only 9% of patients required transfusions. QoL improved significantly in patients with Hb response (p<0.01) and was maintained in non-responders (p>or=0.578). Epoetin beta was effective in preventing severe anaemia in lung cancer patients receiving platinum-based chemotherapy.

Early intervention with epoetin beta prevents severe anaemia in patients with solid tumours receiving platinum-based chemotherapy: results of the NeoPrevent study.

BACKGROUND: Anaemia is common during platinum-based chemotherapy. This study aimed to evaluate the efficacy and safety of epoetin beta in the prevention of severe anaemia in patients with solid tumours receiving concomitant platinum therapy. PATIENTS AND METHODS: In this open-label, single-arm study, patients (n = 255) with solid tumours and haemoglobin (Hb) levels 1 g/dl from baseline) plus patients whose Hb levels remained +/- 1 g/dl of baseline throughout the study] was observed in 234 patients (92%). Response to epoetin beta was rapid. Of the 159 patients achieving a Hb response, 139 (87%) had Hb levels > 1 g/dl of baseline within 4 weeks of treatment initiation. Mean Hb levels had improved from 10.8 +/- 1.0 g/dl at baseline to 12.2 +/- 1.8 g/dl by the final visit. Quality of life measured by linear analogue scale assessment significantly (P < 0.01) improved in patients achieving a Hb response (n = 159). CONCLUSIONS: Epoetin beta effectively prevents anaemia in most patients with solid tumours receiving concurrent platinum-based chemotherapy.

Clinical role of Sm-153 EDTMP in the treatment of painful bone metastatic disease.

PURPOSE: Sm-153 EDTMP is an effective treatment of painful bone metastases from different neoplasms. However, there are few studies describing clinical experience with this therapeutic modality. The aim of this clinical study was to evaluate the efficacy of Sm-153 EDTMP in a group of patients with skeletal metastases and poor pain control with conventional therapies. MATERIALS AND METHODS: Sixty-four patients with painful bone metastases treated with Sm-153 EDTMP were retrospectively evaluated. Nine patients were treated twice. The most common primaries were breast in 28 cases (44%) and prostate in 27 (41%). Treatment efficacy was assessed by a visual analog scale, analgesic consumption, and performance status before and after treatment. Response was graded as complete, moderate, or minor. Toxicity evaluation included analytic parameters (blood counts, renal function) and clinical follow up. RESULTS: Efficacy and toxicity were evaluated separately for each dose (total doses: 73), and complete follow up was only possible in 62 of 73 administrations. The response rate was 85% (21% complete, 40% moderate, and 24% minor). Onset of improvement took place a median of 7 days after Sm-153 EDTMP administration, and pain relief persisted for a mean of 3 months. No relevant toxicity was found in the early phase. Myelotoxicity appeared in 29% of the administrations and was mild in most cases (there was one case of grade 4 leukopenia). CONCLUSIONS: Sm-153 EDTMP is a good therapeutic option for patients with painful bone metastases. It is an effective treatment of pain relief without major secondary effects.

Long term responses with cetuximab therapy in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is responsible for most of the deaths associated with primary brain tumors. Standard treatment includes maximal surgical resection followed by chemotherapy and concomitant radiotherapy. Most patients, however, recur shortly after treatment. Second line treatment has little efficacy and the majority of patients die soon from the disease. Recent advances in molecular biology have implicated the epidermal growth factor receptor (EGFR) signaling pathways in the progression and resistance to standard therapies for GBM. This has prompted the evaluation of EGFR tyrosine- kinase inhibitors with encouraging results. Cetuximab is a monoclonal antibody targeted against the extra cellular domain of the EGFR with activity against different tumor types, either alone or in combination with chemotherapy and/or radiation therapy. Here we describe three patients with recurrent, heavily pretreated, EGFR expressing GBM who responded to treatment with single agent cetuximab.

High-throughput techniques in breast cancer: a clinical perspective.

High-throughput technologies such as DNA-microarrays, RT-PCR and proteomics can improve the prognostic and predictive information acquired from classical parameters. Unlike information gathered by classical methods, high-throughput technologies can accurately inform clinicians on patient response to adjuvant therapy or those who will resist the effect of that therapy. Studies performed in breast cancer with high-throughput techniques have focused on tumour biology, prognosis, prediction of response to a few agents and, more recently, early diagnosis. However, further refinement is needed before these techniques become part of clinical routine. In the meantime, they will be used in clinical investigation, particularly in the areas of hormonal therapy and adjuvant chemotherapy, where modest improvements in the capacity of prediction can benefit many women. Close cooperation among clinicians, pathologists and basic investigators is essential to take high-throughput techniques to daily practice. New diagnostic tools will be complex but they will provide valuable patient information.

Nutrition and pharyngeal cancer: results from a case-control study in Spain.

BACKGROUND: Oropharyngeal and hypopharyngeal cancer is increasing all over the world, frequently affecting more and more women and younger individuals and not only the typical 50- to 60-year-old heavy smoker and drinking man. In addition, 5-year overall survival rate remains poor (30% to 40% in most series), despite advances in treatment. Therefore, it is crucial to understand as accurately as possible the risk factors for these malignancies to improve primary prevention. METHODS: We report the results from a case-control study of pharyngeal cancer risk factors conducted in Spain involving 232 consecutive patients who were gender- and age-matched with 232 controls. Data were collected by interviewer-administered personal interview. RESULTS: Our results show that low intake of fruit, fruit juice, uncooked vegetables, dietary fiber-containing foods (legume and cereals), fish, milk, and dairy products is an independent risk factor for pharyngeal cancer and that high consumption of meat and fried foods also increases the risk once data are adjusted for tobacco smoking and alcohol drinking. CONCLUSIONS: Although findings for fruit, juice, and uncooked vegetables are in accordance with those from other authors and can be explained on a biologic basis, the relationship between pharyngeal cancer and dietary excess of saturated fatty acids needs experimental investigation. Findings for milk, dairy products, and fish also warrant more detailed epidemiologic research because of conflicting data reported in the literature and because of the reportedly ambiguous role of retinol in human cancers. No conclusive explanations for the protective effect of dietary fiber-containing foods can be put forward today. Our results are uniquely attributable to oropharyngeal and hypopharyngeal cancers because of the small size of our nasopharyngeal cancer subsample.