Optimizing therapeutic strategies in advanced bladder cancer: update on chemotherapy and the role of targeted agents.

M-VAC (cisplatin, methotrexate, adriamycin, vinblastine) combination chemotherapy has been the standard of care in fit patient with advanced urothelial tumors for long time. Phase III trials have evaluated new combinations such as gemcitabine/cisplatin, carboplatin/paclitaxel, docetaxel/cisplatin and interferon-alpha/5-fluorouracil/cisplatin. Even though these new regimens have failed to demonstrate superiority in terms of overall survival when compared to the classical M-VAC, the combination of gemcitabine/cisplatin has proved to be a new standard alternative showing more favorable toxicity profile and similar efficacy. Along the same line, the addition of a third agent (TCG) has been studied in a large phase III EORTC trial. This study shows a trend in favor of the triplet and suggests different patterns of chemosensitivity favoring primary bladder carcinoma. In addition to the new active drug combinations the role of targeted agents as monotherapy, in combination with chemotherapy or as maintenance post-chemotherapy is currently under study. Finally, chemotherapy optimization using clinical and molecular markers predicting chemosensitivity and prognosis are emerging.

Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy.

BACKGROUND: Customizing chemotherapy on the basis of chemosentitivity prediction may improve outcome in advanced bladder cancer patients. Since DNA damaging agents are the cornerstones of therapy, we hypothesized that levels of DNA repair genes could predict survival. PATIENTS AND METHODS: Messenger RNA expression levels of excision repair cross complementing 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunit M1 (RRM1) and caveolin-1 were determined by RT-PCR in tumor DNA from 57 advanced and metastatic bladder cancer patients treated with either gemcitabine/cisplatin or gemcitabine/cisplatin/paclitaxel (Taxol). Levels were correlated with survival, time to disease progression and chemotherapy response. RESULTS: Median survival was significantly higher in patients with low ERCC1 levels (25.4 versus 15.4 months; P = 0.03) (median follow-up 19 months). A trend towards longer time to progression was observed in patients with tumors expressing low levels of all markers. Levels of RRM1, BRCA1 and caveolin-1, however, failed to predict the survival and a clear link with chemotherapy response could not be established. On multivariate analysis with pretreatment prognostic factors, ERCC1 emerged as an independent predictive factor for survival. CONCLUSION: The results of the study indicate that ERCC1 may predict survival in bladder cancer treated by platinum-based therapy.

Gemcitabine in the treatment of advanced transitional cell carcinoma of the urothelium.

M-VAC (cisplatin, methotrexate, adriamycin, vinblastine) combination chemotherapy has been for long time the standard of care in fit patient with advanced urothelial tumors. Gemcitabine/cisplatin with similar results and an improved toxicity profile has proved to be a new standard alternative. Whether or not we can improve survival with newer triplet regimens will depend upon the results of ongoing phase III trials. In addition to the new active drug combinations and targeted therapies, new approaches are emerging for treatment. Chemotherapy optimization using molecular markers predicting chemosensitivity are being applied. There is an obvious need to incorporate in clinical trials a systematic translational approach to explain both our successes and our failures.

New drugs and new approaches in metastatic bladder cancer.

The median survival of patients with metastatic cancer of the urothelium who receive best supportive care only in 4-6 months. With the introduction of combination chemotherapy regimens including cisplatin and methotrexate for the management of metastatic urothelial cancer, median overall survival has doubled. Nevertheless, death due to cancer ultimately occurs in more than 80% of these patients, thus more effective therapy is required. The new available treatment modalities range from new combinations of conventional chemotherapeutic agents to combinations incorporating novel drugs like gemcitabine and the taxanes. These new combinations incorporate the new active agents in two, three or multiple drug combinations, administered either in one regimen or sequentially in various combinations and schedules intended to improve the outcome of bladder cancer patients. Ongoing phase III studies will help to define the role of these new combinations in the treatment of advanced bladder cancer. The improved understanding of the molecular biology of urothelial malignancies is helping to define the role of new prognostic indices that can direct the most appropriate choice of treatment for advanced disease. In addition, advances in the molecular biology of urothelial malignancies may allow identification of specific genetic lesions and biochemical pathways upon which future therapeutic approaches can be focused. The integration of newer biologic agents, probably to supplement rather than to supplant chemotherapeutic drugs, should be a primary direction of research with the objective to interfere with multiple aspects of bladder cancer progression.

New chemotherapy combinations for advanced bladder cancer.

Transitional cell carcinoma of the urothelium is considered a chemosensitive malignancy. Until recently, the methotrexate, vinblastine, doxorubicin and cisplatin combination has been considered the standard for treating this disease. The development of new chemotherapeutic agents such as gemcitabine and the taxanes has opened up promising new perspectives in the treatment of this disease. However, the preliminary phase II data must be confirmed in adequately conducted phase III trials.

Absceso de lengua. A propósito de un caso y revisión de la bibliografía / Tongue abscess. A case report and literature review

Presentamos un caso de absceso de lengua por Streptococcus faecalis. Los abscesos de lengua son una patología extremadamente rara en nuestro medio, por lo que se hace dificil su diagnóstico. La tomografía computerizada aporta una valiosa información para llegar al diagnóstico de esta entidad. El tratamiento se basa en la incisión y drenaje con posterior terapéutica antimicrobiana (AU)

We report a case of tongue abscess due to Streptococcus faecalis. Tongue abscesses are rare infections in our region, which makes the diagnosis difficult. The CT scan provides important diagnostic information for this disease. Treatment is surgical incision and drainage associated with antibiotic therapy (AU)

[Tongue abscess. Report of a case and bibliographic review]. / Absceso de lengua. A propósito de un caso y revisión de la bibliografía.

We report a case of tongue abscess due to Streptococcus faecalis. Tongue abscesses are rare infections in our region, which makes the diagnosis difficult. The CT scan provides important diagnostic information for this disease. Treatment is surgical incision and drainage associated with antibiotic therapy.

[The CO2 laser treatment of benign laryngeal stenosis in patients undergoing horizontal supraglottic laryngectomy]. / Tratamiento con láser CO2 de las estenosis laríngeas benignas en pacientes intervenidos de laringectomía horizontal supraglótica.

One of the indications for CO2 laser surgery in benign laryngeal disease is the treatment of stenosis. Thirty-two patients with laryngeal stenosis after partial horizontal surgery of the larynx were treated with endoscopic CO2 laser surgery. The presence of laryngeal stenosis either impeded decannulation or produced dyspnea in decannulated patients. Results were satisfactory, with 84% of patients decannulated within 2 or 3 months of laser surgery.

[Rendu-Osler disease. Follow-up of 6 patients treated by embolization. Nasal telecobaltotherapy in a refractory case]. / Enfermedad de Rendu-Osler. Seguimiento de seis casos tratados mediante embolización. Telecobaltoterapia nasal en un caso refractario.

Patients with Rendu-Osler-Weber disease can present severe nose bleeding. The treatment of 6 patients with this condition is reported. Supraselective embolization was the treatment of choice. One patient showed no improvement with embolization and suffered massive nosebleed requiring blood transfusion. After a review of the literature, the nasal cavity was irradiated.s.

Randomized trial of adjuvant chemotherapy with mitomycin plus ftorafur versus mitomycin alone in resected locally advanced gastric cancer.

PURPOSE: We performed a clinical trial to determine whether postoperative adjuvant chemotherapy with two drugs versus one drug could prolong survival. PATIENTS AND METHODS: From 1985 to 1996, 85 patients with completely resected locally advanced gastric cancer were enrolled. The subjects were randomized into two treatment groups, as follows: mitomycin (MMC) 10 to 20 mg/m2 intravenously (i.v.) on day 1 every 6 weeks plus ftorafur (FT) 500 mg/m2/d for 36 consecutive days; or MMC alone, 10 to 20 mg/m2 i.v. every 6 weeks. All courses were repeated four times. RESULTS: After a median follow-up duration of 62 months, the overall 5-year survival rates were 67% for the MMC-FT group versus 44% for the MMC group (P = .04). Subgroup analysis to compare survival curves using the method of Mantel-Cox showed survival rates significantly in favor of the MMC-FT group in the subsets of patients with node-negative disease (P = .01) and those whose disease was stage IB or II (P = .008). CONCLUSION: Significantly better survival results were observed for MMC-FT versus MMC alone. Subset analysis suggest a strong benefit in patients with node-negative and early-stage resected gastric cancer.