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

Bladder cancer occurs in the majority of cases in males. It represents the seventh most common cancer and the ninth most common cause of cancer deaths for men. Transitional cell carcinoma is the most predominant histological type. Bladder cancer is highly chemosensitive. In metastatic setting, chemotherapy based on cisplatin should be considered as standard treatment of choice for patients with good performance status (0-1) and good renal function-glomerular filtration rate (GFR) > 60 mL/min. The standard treatment is based on cisplatin chemotherapy regimens type MVAC, HD-MVAC, gemcitabine plus cisplatin (GC) or dose dense GC. In unfit patients, carboplatin based regimes; gemcitabine plus carboplatin or methotrexate plus carboplatin plus vinblastine (MCAVI) are reasonable options. The role of targeted therapies when used alone, or in combination with chemotherapy, or in maintenance, was evaluated; targeting angiogenesis seem to be very promising. The purpose of this literature review is to highlight the role of chemotherapy in the management of advanced transitional cell carcinoma of the bladder.

show abstract

“…The combination of gemcitabine with cisplatin (GC) has further improved these results with higher ORR (57%) and CR (15 to 21%) [17]. …”

Section: - Chemotherapy In Metastatic Diseasementioning

confidence: 99%

Chemotherapy in advanced bladder cancer: current status and future

Ismaili¹,

Amzerin

Fléchon

2011

J Hematol Oncol

View full text Add to dashboard Cite

show abstract

“…[5][6][7][8] Consecutive studies reported low response rates both with GC and MVAC (49-65%, and 46-65%, respectively). [9,10] So, triple chemotherapy regimens were applied, however, they were more toxic and less effective. [1] The combination of cisplatin with taxanes provided promising effectiveness with improved overall response rate (ORRs) of 50-70 percent [11][12][13][14] , but it remained inferior to the MVAC as shown by a phase III randomized study (ORR was 37.4% vs. 54.2% p=0.017, TTP was 6.1 vs. 9.4 months, p=0.003).…”

Section: Introductionmentioning

confidence: 99%

Maintenance treatment with gemcitabine have a promising activity on metastatic bladder cancer survival

Kuş

Aktaş

2017

Turkish Journal of Urology

View full text Add to dashboard Cite

Objective: To investigate the effects of gemcitabine maintenance treatment on survival in patients with metastatic bladder cancer. Material and methods:Gemcitabine maintenance monotherapy was administered following the standard platinum-gemcitabine therapy in patients with metastatic bladder cancer. Patients who had responded to standard treatment received maintenance gemcitabine therapy as 1000 mg/m 2 on days 1 and 8 every three weeks until progression or development of unacceptable toxicity. The following clinical factors were noted: performance status, age, sex, stage, site of metastasis, choice of cisplatin-gemcitabine or carboplatin-gemcitabine, response rates to the initial chemotherapy. Progression-free survival (PFS) and overall survival (OS) for standard treatment, and following gemcitabine monotreatment and for maintenance gemcitabine therapy were calculated using Kaplan-Meier method.Results: A total of 88 patients with metastatic bladder cancer treated between February 2009 to October 2015 were evaluated retrospectively and 23 patients (26.1%) who had responded to six cycles of platinumgemcitabine treatment were included in this study. Maintenance gamcitabine was administered for a median of 7 times (range 3-14 times). Grade 3 hematotoxicity according to the criteria of the Common Terminology Criteria of Adverse Events was observed in 7 (30.4%) patients. Median PFS of patients was 46 (range: 30-82) weeks for platinum-based treatment plus maintenance gemcitabine therapy. A higher median PFS was obtained in patients who were <65 year-olds, without organ metastasis with objective response rate, however, it was statistically insignificant. Conclusion:Gemcitabine maintenance therapy in metastatic bladder cancer patients who did not shown progression after the standard platinum-gemcitabine treatment contributes to survival and presents low toxicity profile, when compared to historical controls.

show abstract

“…Based on its low toxicity and good tolerability and response, GEM has been described as the single most effective agent for bladder cancer (14). …”

Section: Introductionmentioning

confidence: 99%

Dual targeting of heat shock proteins 90 and 70 promotes cell death and enhances the anticancer effect of chemotherapeutic agents in bladder cancer

Sato

et al. 2014

Oncology Reports

View full text Add to dashboard Cite

Heat shock proteins (HSPs), which are molecular chaperones that stabilize numerous vital proteins, may be attractive targets for cancer therapy. The aim of the present study was to investigate the possible anticancer effect of single or dual targeting of HSP90 and HSP70 and the combination treatment with HSP inhibitors and chemotherapeutic agents in bladder cancer cells. The expression of HSP90 and the anticancer effect of the HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) coupled with cisplatin, docetaxel, or gemcitabine were examined using immunohistochemistry, quantitative real-time PCR, cell growth, flow cytometry, immunoblots and caspase-3/7 assays. The expression of HSP70 under HSP90 inhibition and the additive effect of HSP70 inhibitor pifithrin-μ (PFT-μ) were examined by the same assays and transmission electron microscopy. HSP90 was highly expressed in bladder cancer tissues and cell lines. 17-AAG enhanced the antiproliferative and apoptotic effects of each chemotherapeutic agent. 17-AAG also suppressed Akt activity but induced the upregulation of HSP70. PFT-μ enhanced the effect of 17-AAG or chemotherapeutic agents; the triple combination of 17-AAG, PFT-μ and a chemotherapeutic agent showed the most significant anticancer effect on the T24 cell line. The combination of 17-AAG and PFT-μ markedly suppressed Akt and Bad activities. With HSP90 suppression, HSP70 overexpression possibly contributes to the avoidance of cell death and HSP70 may be a key molecule for overcoming resistance to the HSP90 inhibitor. The dual targeting of these two chaperones and the combination with conventional anticancer drugs could be a promising therapeutic option for patients with advanced bladder cancer.

show abstract

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

Cited by 22 publications

References 43 publications

Chemotherapy in advanced bladder cancer: current status and future

Chemotherapy in advanced bladder cancer: current status and future

Maintenance treatment with gemcitabine have a promising activity on metastatic bladder cancer survival

Dual targeting of heat shock proteins 90 and 70 promotes cell death and enhances the anticancer effect of chemotherapeutic agents in bladder cancer

Contact Info

Product

Resources

About