taxane and Urinary-Bladder-Neoplasms

Radical cystectomy remains the standard of care for muscle-invasive bladder cancer, while for high-risk superficial carcinoma an organ-preserving approach, including transurethral resection (TUR) and intravesical therapy, is recommended. This review summarizes the radiochemotherpeutic options for high risk T1 or muscle-invasive bladder cancer - as an alternative for/or neoadjuvant therapy before radical surgery. Multimodality therapy, including TUR, radiation, and chemotherapy, is associated with recurrence and progression rates of 30 % and 15 %, respectively, in high-risk T1 bladder cancer. For muscle-invasive disease, five-year survival rates in the range of 50 % to 60 % have been published, which is comparable to primary cystectomy series. Approximately 80 % of the surviving patients maintained their own, well functioning bladder. Close coordination among all disciplines is required to achieve optimal results. An integral part of the concept is salvage cystectomy for non-responders or muscle-invasive recurrences. Ideal candidates for the organ-preserving approach are those with early-stage unifocal tumours (T1/T2). Preoperative radiochemotherapy is likely to improve the results of cystectomy alone in patients with locally advanced bladder cancer (T3b, T4).

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Bridged-Ring Compounds; Chemotherapy, Adjuvant; Cisplatin; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Cystectomy; Deoxycytidine; Fluorouracil; Follow-Up Studies; Gemcitabine; Humans; Multicenter Studies as Topic; Neoadjuvant Therapy; Neoplasm Staging; Preoperative Care; Radiography; Radiotherapy Dosage; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Risk Factors; Salvage Therapy; Taxoids; Time Factors; Urinary Bladder; Urinary Bladder Neoplasms

Recent progress in the treatment for urothelial cancer is reviewed, especially concerning systemic chemotherapy and surgical techniques. A guideline for chemotherapy of urothelial cancer according to clinical stage is shown on the basis of evidence level in Japan. MVAC chemotherapy is regarded as the gold standard for advanced metastatic urothelial cancer. Randomized controlled trial revealed that gemcitabine in combination with cisplatin (GC therapy) has an efficacy similar to MVAC and is less toxic. Thus, GC therapy will become the standard treatment for advanced metastatic urothelial cancer instead of MVAC. Many chemotherapeutic regimens including gemcitabine and taxane have been introduced for patients with MVAC refractory or recurrent urothelial cancer. It was not yet clarified whether neoadjuvant chemotherapy provides survival benefits. Recent metaanalysis, however, revealed that neoadjuvant chemotherapy, especially cisplatin-based chemotherapy, has a survival advantage compared with total cystectomy alone. Intravesical BCG instillation is the standard treatment for carcinoma in situ and prophylaxis of recurrence for high-risk superficial bladder cancer. For higher efficacy and lower adverse effect, maintenance instillation and low-dose therapy are proposed, respectively, but further investigation is needed. Laparoscopic surgery in the urological field is widely performed and regarded as a minimally invasive surgery. Laparoscopic nephroureterectomy for patients with upper urinary tract cancer is reported to show the same efficacy at point of cancer control in comparison with traditional open surgery. Endoscopic treatment for upper tract urothelial cancer using laser can be safe and effective for a properly selected patient with a normal contralateral kidney.

Topics: Administration, Intravesical; Antineoplastic Combined Chemotherapy Protocols; BCG Vaccine; Bridged-Ring Compounds; Cisplatin; Deoxycytidine; Doxorubicin; Endoscopy, Gastrointestinal; Evidence-Based Medicine; Gemcitabine; Humans; Laparoscopy; Laser Therapy; Methotrexate; Neoadjuvant Therapy; Taxoids; Urinary Bladder Neoplasms; Urologic Neoplasms; Vinblastine

Invasive bladder cancer is a chemotherapy-sensitive neoplasm. Historically, the development of cisplatin (Platinol)-based chemotherapy regimens has represented an important advance for patients with metastatic disease. More recently, investigations of new agents, such as gemcitabine (Gemzar) and paclitaxel (Taxol), have resulted in further options for these patients. Randomized trials comparing new regimens with cisplatin-based therapies have been initiated. The role of chemotherapy in the adjuvant and neoadjuvant settings is an area that is undergoing active investigation. The application of prognostic biological markers to risk-stratify patients has resulted in new avenues of investigation in these ongoing early disease trials.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bridged-Ring Compounds; Carboplatin; Deoxycytidine; Gemcitabine; Humans; Neoadjuvant Therapy; Paclitaxel; Taxoids; Urinary Bladder Neoplasms

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

Perioperative chemotherapy is likely to improve survival in both the neoadjuvant and the adjuvant setting. Therefore, it is an integral part of the modern treatment of patients with muscle-invasive urothelial bladder cancer. All patients who are suitable for cisplatin-based chemotherapy should be involved in a corresponding concept.Cisplatin-based combinations are standard regimens in the perioperative and palliative systemic treatment of urothelial cancer. Carboplatin is only an inferior substitute for "unfit" patients in the palliative treatment situation. Vinflunine may be used as a second-line agent in case of recurrence after palliative first-line treatment or in patients presenting with rapid progression after perioperative treatment. Alternatively, taxane or taxane-based combinations can be used in these situations.New therapeutic options may include the use of immune checkpoint inhibitors, which have shown promising results in early studies. Two substances have already been approved by the FDA for the treatment of advanced/metastatic urothelial cancer following platin-based upfront treatment. Other future options may be "tailored" treatment concepts based on the molecular pathogenesis of the individual patient. However, extensive pre-clinical work is still required for this approach.. Eine perioperative Chemotherapie verbessert wahrscheinlich sowohl in einem neoadjuvanten als auch in einem adjuvanten Konzept das Überleben des Patienten. Damit ist sie ein integraler Teil der modernen Therapie von Patienten mit einem muskelinvasiven Harnblasenkarzinom. Jeder Patient, der für eine Cisplatin-basierte Chemotherapie geeignet ist, sollte in ein entsprechendes Konzept eingebunden werden.Standard sowohl in der perioperativen als auch in der palliativen Systemtherapie des Urothelkarzinoms sind Cisplatin-basierte Kombinationstherapien. Carboplatin stellt nur bei „unfitten“ Patienten in der palliativen Therapiesituation einen möglichen Ersatz dar, in der perioperativen Systemtherapie besitz es keinen Stellenwert. Im Falle eines Rezidivs nach einer palliativen Erstlinientherapie oder bei einem schnellen Progress nach perioperativer Therapie kann eine Zweitlinientherapie mit Vinflunin durchgeführt werden. Alternativ dazu können auch Taxane oder Taxan-basierte Kombinationen zum Einsatz kommen.Neue Therapiemöglichkeiten sind der Einsatz von Immuncheckpoint-Inhibitoren, welche in ersten Studien vielversprechende Ergebnisse zeigten. Erste Zulassungen durch die FDA sind für die Therapie des metastasierten/fortgeschrittenen Urothelkarzinoms bereits erfolgt. Andere zukünftige Optionen sind „maßgeschneiderte“ Therapiekonzepte, die auf der Molekularpathogenese des individuellen Patienten beruhen. Hier sind jedoch noch weitreichende präklinische Arbeiten erforderlich.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Cisplatin; Humans; Neoadjuvant Therapy; Taxoids; Urinary Bladder Neoplasms; Vinblastine

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