Second Line Chemotherapy for Advanced and Metastatic Urothelial Carcinoma: Vinflunine and Beyond—A Comprehensive Review of the Current Literature

Oing, Christoph; Rink, Michael; Seidel, Christoph; Amsberg, Gunhild von; Bokemeyer, Carsten

doi:10.1016/j.juro.2015.06.115

Cited by 100 publications

(68 citation statements)

References 38 publications

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“…There is currently no USA Food and Drug Administration (FDA)-approved treatment subsequent to first-line chemotherapy in the USA. However, taxanes are commonly used for palliative chemotherapy based on modest response rates in several small, nonrandomized phase II trials (4). …”

Section: Introductionmentioning

confidence: 99%

Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells

et al. 2017

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Nanoparticle albumin-bound (nab)-paclitaxel appears to exhibit better response rates in patients with metastatic urothelial cancer of the bladder whom are pretreated with nab-paclitaxel compared with conventional paclitaxel. Paclitaxel may induce multidrug resistance in patients with cancer, while the mechanisms of resistance against paclitaxel are manifold. These include reduced function of pro-apoptotic proteins, mutations of tubulin and overexpression of the drug transporter adenosine 5′-triphosphate-binding cassette transporter subfamily B, member 1 (ABCB1). To evaluate the role of ABCB1 in nab-paclitaxel resistance in urothelial cancer cells, the bladder cancer cell lines T24 and TCC-SUP, as well as sub-lines with acquired resistance against gemcitabine (T24rGEMCI20 and TCC-SUPrGEMCI20) and vinblastine (T24rVBL20 and TCC-SUPrVBL20) were examined. For the functional inhibition of ABCB1, multi-tyrosine kinase inhibitors with ABCB1-inhibiting properties, including cabozantinib and crizotinib, were used. Additional functional assessment was performed with cell lines stably transduced with a lentiviral vector encoding for ABCB1, and protein expression was determined by western blotting. It was indicated that cell lines overexpressing ABCB1 exhibited similar resistance profiles to nab-paclitaxel and paclitaxel. Cabozantinib and crizotinib sensitized tumor cells to nab-paclitaxel and paclitaxel in the same dose-dependent manner in cell lines overexpressing ABCB1, without altering the downstream signaling of tyrosine kinases. These results suggest that the overexpression of ABCB1 confers resistance to nab-paclitaxel in urothelial cancer cells. Additionally, small molecules may overcome resistance to anticancer drugs that are substrates of ABCB1.

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Section: Introductionmentioning

confidence: 99%

Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells

et al. 2017

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“…However, other agents are more widely used globally. 3,5,6 At the time this study started, no chemotherapy agents were approved in this setting in the United States.…”

Section: Introductionmentioning

confidence: 99%

Randomized Phase II Study Investigating Pazopanib Versus Weekly Paclitaxel in Relapsed or Progressive Urothelial Cancer

Jones

Hussain

Protheroe

et al. 2017

JCO

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Two previous single-arm trials have drawn conflicting conclusions regarding the activity of pazopanib in urothelial cancers after failure of platinum-based chemotherapy. Patients and MethodsThis randomized (1:1) open-label phase II trial compared the efficacy of pazopanib 800 mg orally with paclitaxel (80 mg/m 2 days 1, 8, and 15 every 28 days) in the second-line setting. The primary end point was overall survival (OS). ResultsBetween August 2012 and October 2014, 131 patients, out of 140 planned, were randomly assigned. The study was terminated early on the recommendation of the independent data monitoring committee because of futility. Final analysis after the preplanned number of deaths (n = 110) occurred after a median follow-up of 18 months. One hundred fifteen deaths had occurred at the final data extract presented here. Median OS was 8.0 months for paclitaxel (80% CI, 6.9 to 9.7 months) and 4.7 months for pazopanib (80% CI, 4.2 to 6.4 months). The hazard ratio (HR) adjusted for baseline stratification factors was 1.28 (80% CI, 0.99 to 1.67; one-sided P = .89). Median progression-free survival was 4.1 months for paclitaxel (80% CI, 3.0 to 5.6 months) and 3.1 months for pazopanib (80% CI, 2.7 to 4.6 months; HR, 1.09; 80% CI, 0.85 to 1.40; onesided P = .67). Discontinuations for toxicity occurred in 7.8% and 23.1% for paclitaxel and pazopanib, respectively. ConclusionPazopanib did not have greater efficacy than paclitaxel in the second-line treatment of urothelial cancers. There was a trend toward superior OS for paclitaxel.

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“…Most of the chemotherapy agents have been tested in phase 2 studies. Paclitaxel, docetaxel, oxaliplatin, pemetrexed, nab-paclitaxel, ifosfamida, among others, have a response rate of around 20%, without having proven a global survival benefit [48]. Combined use of chemotherapy agents increases the response rate and DFS [49].…”

Section: First-line Therapy Of Locally Advanced and Metastatic Diseasementioning

confidence: 99%

SEOM Clinical Guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2016)

et al. 2016

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The goal of this article is to provide recommendations for the diagnosis and treatment of muscle-invasive and metastatic bladder cancer. The diagnosis of muscle-invasive bladder cancer is made by pathologic evaluation after transurethral resection. Recently, a molecular classification has been proposed. Staging of muscle-invasive bladder cancer must be done by computed tomography scans of the chest, abdomen and pelvis and classified on the basis of UICC system. Radical cystectomy and lymph node dissection are the treatment of choice. In muscle-invasive bladder cancer, neoadjuvant chemotherapy should be recommended in patients with good performance status and no renal function impairment. Although there is insufficient evidence for use of adjuvant chemotherapy, its use must be considered when neoadjuvant therapy had not been administered in high-risk patients. Multimodality bladder-preserving treatment in localized disease is an alternative in selected and compliant patients for whom cystectomy is not considered for clinical or personal reasons. In metastatic disease, the first-line treatment for patients must be based on cisplatin-containing combination. Vinflunine is the only drug approved for use in second line in Europe. Recently, immunotherapy treatment has demonstrated activity in this setting.

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Second Line Chemotherapy for Advanced and Metastatic Urothelial Carcinoma: Vinflunine and Beyond—A Comprehensive Review of the Current Literature

Abstract: Response rates and survival are poor after second line chemotherapy for advanced or metastatic urothelial carcinoma. To improve outcomes of salvage treatment novel biologically targeted drugs as monotherapy or as part of a combination with conventional cytostatics are urgently needed.

Cited by 100 publications

References 38 publications

Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells

Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells

Randomized Phase II Study Investigating Pazopanib Versus Weekly Paclitaxel in Relapsed or Progressive Urothelial Cancer

SEOM Clinical Guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2016)

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