taxane and Carcinoma--Transitional-Cell

Cisplatin-based combination chemotherapy such as methotrexate, vinblastine, adriamycin and cisplatin produces durable improvements in survival in only a minority of patients. Therefore, other therapeutic options and strategies are clearly needed. Strategies include increasing the dose of chemotherapy, modifying the sequencing of chemotherapy, and new therapeutic agents. This paper reviews recent work on high-dose chemotherapy, currently available chemotherapeutic agents and combinations, with an emphasis on gemcitabine and the taxanes. New strategies such as monoclonal antibody therapy and molecular targeted small molecule therapy are becoming a reality in the treatment of many diseases. The rationale for using epidermal growth factor receptor targeted therapies is also reviewed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Transitional Cell; Cisplatin; Deoxycytidine; Doxorubicin; Female; Gemcitabine; Humans; Male; Methotrexate; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Randomized Controlled Trials as Topic; Severity of Illness Index; Survival Analysis; Taxoids; Treatment Outcome; Urinary Bladder Neoplasms; Urologic Neoplasms; Urothelium; Vinblastine

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.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Transitional Cell; Cisplatin; Clinical Trials as Topic; Deoxycytidine; Dose-Response Relationship, Drug; Doxorubicin; Drug Combinations; Female; Gemcitabine; Humans; Male; Methotrexate; Neoplasm Metastasis; Platinum; Prognosis; Severity of Illness Index; Survival Analysis; Taxoids; Urinary Bladder Neoplasms; Vinblastine

The combination of methotrexate, vinblastine, Adriamycin, and cisplatin (MVAC) has been the standard therapy for transitional cell carcinoma for over a decade. Despite evidence that MVAC can improve outcome in comparison with single drugs or other combinations in this disease, only a small fraction of patients (less than 4%) become long-term survivors, and the regimen is quite toxic. Attempts to improve upon the MVAC regimen have partially ameliorated its toxicity, but they have not clearly improved outcome. Recently, a number of new chemotherapeutic agents have become available. This report summarizes the current experience with these agents and combinations.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Transitional Cell; Cisplatin; Deoxycytidine; Doxorubicin; Gallium; Gemcitabine; Humans; Ifosfamide; Methotrexate; Neoplasm Metastasis; Taxoids; Urinary Bladder Neoplasms; Vinblastine

Trials of salvage therapy for advanced urothelial carcinoma have required prior platinum-based therapy. This practice requires scrutiny because non-platinum-based first-line therapy may be offered to cisplatin-ineligible patients.. Data of patients receiving salvage systemic chemotherapy were collected. Data on prior first-line platinum exposure were required in addition to treatment-free interval, hemoglobin, Eastern Cooperative Oncology Group performance status, albumin, and liver metastasis status. Cox proportional hazard regression was used to evaluate their association with overall survival (OS) after accounting for salvage single-agent or combination chemotherapy.. Data were obtained from 455 patients previously exposed to platinum-based therapy and 37 not exposed to platinum. In the group exposed to prior platinum therapy, salvage therapy consisted of a single-agent taxane (n = 184) or a taxane-containing combination chemotherapy (n = 271). In the group not exposed to prior platinum therapy, salvage therapy consisted of taxane or vinflunine (n = 20), 5-fluorouracil (n = 1), taxane-containing combination chemotherapy (n = 12), carboplatin-based combinations (n = 2), and cisplatin-based combinations (n = 2). The median OS for the prior platinum therapy group was 7.8 months (95% confidence interval, 7.0, 8.1), and for the group that had not received prior platinum therapy was 9.0 months (95% confidence interval, 6.0, 11.0; P = .50). In the multivariable analysis, prior platinum therapy versus no prior platinum exposure did not confer an independent impact on OS (hazard ratio, 1.10; 95% confidence interval, 0.75, 1.64; P = .62).. Prior platinum- versus non-platinum-based chemotherapy did not have a prognostic impact on OS after accounting for major prognostic factors in patients receiving salvage systemic chemotherapy for advanced urothelial carcinoma. Lack of prior platinum therapy should not disqualify patients from inclusion onto trials of salvage therapy.

Topics: Aged; Antineoplastic Agents; Bridged-Ring Compounds; Carcinoma, Transitional Cell; Female; Humans; Male; Middle Aged; Organoplatinum Compounds; Prognosis; Salvage Therapy; Survival Analysis; Taxoids; Treatment Outcome; Urologic Neoplasms

Topics: Antineoplastic Agents; Bridged-Ring Compounds; Carcinoma, Transitional Cell; Everolimus; Genetic Predisposition to Disease; Humans; Mutation; Neurofibromatosis 2; Taxoids; Treatment Outcome; Urinary Bladder; Urologic Neoplasms

After encouraging results from 2 clinical trials performed at our institution to test intravesical taxane based chemotherapy for bacillus Calmette-Guérin refractory, nonmuscle invasive bladder cancer we designed a study to identify molecular markers linked to the optimal response to such treatment modality.. Included in the institutional review board approved study were 32 patients with nonmuscle invasive, bacillus Calmette-Guérin refractory bladder cancer who received intravesical taxane chemotherapy, that is docetaxel or nanoparticle albumin-bound paclitaxel. Immunophenotype analysis on tissue samples obtained before intravesical taxane therapy was done using a panel of molecular markers, including Ki-67, p53, and the microtubule associated proteins tau and stathmin.. Increased total tau (cytoplasmic and nuclear) and stathmin expression before intravesical taxane therapy was significantly associated with decreased recurrence-free survival (p <0.0001 and 0.007, respectively). A tau positive phenotype was an independent prognostic factor for recurrence-free survival on multivariate analysis (HR 15.66, 95% CI 2.68-91.71, p = 0.002). Neither the proliferation index assessed by Ki-67 expression nor p53 status was significantly associated with recurrence-free survival.. Assessment of tau and stathmin protein expression should be considered to select patients before intravesical taxane based chemotherapy for nonmuscle invasive, bacillus Calmette-Guérin refractory bladder cancer since those who have tumors with low tau/stathmin protein expression show a better response to therapy.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; BCG Vaccine; Biomarkers, Tumor; Bridged-Ring Compounds; Carcinoma, Transitional Cell; Chemotherapy, Adjuvant; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Ki-67 Antigen; Male; Microtubules; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Stathmin; tau Proteins; Taxoids; Treatment Failure; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms