The Role of Taxanes in the Management of Bladder Cancer

Galsky, Matthew D.

doi:10.1634/theoncologist.10-10-792

Cited by 30 publications

(6 citation statements)

References 38 publications

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“…Microtubules are crucial for cell growth and are one of the most successful targets in cancer therapy to date [6]. Paclitaxel is a naturally occurring antimicrotubule agent that has gained widespread acceptance as an active compound against various tumour entities including bladder cancer [7]. For intravesical treatment, paclitaxel is a particularly attractive candidate because it penetrates bladder tissues at a rate of 20 times that of water-soluble drugs like mitomycin C, allowing for prolonged retention of therapeutic doses even after the instilled solution is removed [8].…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel incorporated in hydrophobically derivatized hyperbranched polyglycerols for intravesical bladder cancer therapy

Mugabe¹,

Hadaschik

Kainthan

et al. 2009

BJU International

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C.M. and B.A.H. contributed equally.in Cremophor-EL (Taxol®, Bristol-MyersSquibb). In vivo , nude mice with orthotopic KU7-luc tumours were intravesically instilled with phosphate buffered saline, Taxol, or paclitaxel/HPG-C10-PEG. RESULTSdHPGs are mucoadhesive nanoparticles with hydrodynamic radii of < 10 nm and incorporation of paclitaxel did not affect their size. The release profiles of paclitaxel from dHPGs were characterized by a rapid-release phase followed by a slower sustained-release phase. While the PEI-C18-HPG formulation released only ≈ 40% of the initially incorporated paclitaxel, up to 80% was released from HPG-C10-PEG. Moreover, only paclitaxel/HPG-C10-PEG was stable in acidic urine. In vitro , all paclitaxel formulations potently decreased bladder cancer proliferation although paclitaxel/ HPG-C10-PEG was slightly less cytotoxic than standard Taxol. By contrast, in vivo , the mucoadhesive HPG-C10-PEG formulation of paclitaxel was significantly more effective in reducing orthotopic tumour growth than Taxol and was well tolerated. CONCLUSIONIntravesical administration of mucoadhesive nanoparticulate formulations of paclitaxel might be a promising approach for instillation therapy of patients with nonmuscle-invasive bladder cancer. KEYWORDSbladder cancer, hyperbranched polyglycerols, unimolecular micelles, paclitaxel, intravesical therapy, orthotopic mouse model OBJECTIVETo develop paclitaxel incorporated into unimolecular micelles based on hydrophobically derivatized hyperbranched polyglycerols (dHPGs) for use as mucoadhesive intravesical agents against non-muscle-invasive bladder cancer. MATERIALS AND METHODSTwo different types of dHPGs (HPG-C10-polyethylene glycol (PEG) and polyethyleneimine (PEI)-C18-HPG) were synthesized and paclitaxel was loaded into these using a solvent evaporation method. After physicochemical characterization of the resulting nanoparticles, four human bladder cancer cell lines were incubated with various concentrations of paclitaxel incorporated in dHPGs and the results were compared with those of paclitaxel formulated

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Section: Introductionmentioning

confidence: 99%

Paclitaxel incorporated in hydrophobically derivatized hyperbranched polyglycerols for intravesical bladder cancer therapy

Mugabe¹,

Hadaschik

Kainthan

et al. 2009

BJU International

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“…Paclitaxel has been used in human medicine for the treatment of recurrent or inoperable tumors such as metastatic breast, advanced ovarian, and non-small-cell lung cancers [5,12,15]. Paclitaxel and other taxanes have been used alone and in combination with other drugs to treat bladder tumors in humans, and its effectiveness and safety have been confirmed [2,13]. The use of paclitaxel in the treatment of human cancers and the report of anticancer effects in various canine tumor cell lines have caused paclitaxel to be of interest for the treatment of some malignant tumors in veterinary medicine [1,[7][8]19].…”

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confidence: 99%

“…A three-phase study of oral paclitaxel formulation in human patients with various tumors has been conducted [4,11] In this report, we describe the first use of oral paclitaxel for veterinary (canine) patients. We selected oral paclitaxel for the treatment of bladder tumors in our canine patients for the following three reasons: 1) compared to IV administration, oral administration is easier and confers less stress to the patient, less risk of hypersensitivity reactions, and fewer hospital visits; 2) we were able to receive oral paclitaxel for veterinary clinical application through an agreement with a pharmaceutical company; and 3) we assessed several studies from human medicine which used paclitaxel as either first and second line therapy in the treatment of refractory or recurrent bladder tumors and applied them to canine patient with bladder tumors [2,9,13,18]. We aimed to evaluate the clinical validity of oral paclitaxel in dogs with bladder tumors.…”

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confidence: 99%

Use of oral paclitaxel for the treatment of bladder tumors in dogs

Chae

Yang

et al. 2020

The Journal of Veterinary Medical Science

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An oral paclitaxel formulation that overcomes the hypersensitivity reaction of paclitaxel has been evaluated for safety and efficacy in humans, but not in dogs. We present the first case report on the use of oral paclitaxel in dogs. In this study, oral paclitaxel was well-tolerated in four dogs with either transitional cell carcinoma or prostate cancer; adverse effects were limited to mild neutropenia. Each of the dogs had progressive disease at the end, but clinical responses, including changes in mass size and improvement of clinical symptoms, were confirmed in some of the animals following oral paclitaxel chemotherapy. Although this study is somewhat limited by a small sample size, it suggests that oral paclitaxel may be a chemotherapeutic option for malignant tumors in dogs.

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“…Certain chemotherapeutic agents were reported to act as a radiation sensitizer against tumor cells in addition to their direct cytotoxic effects. [ 14 15 ] CDDP has also been shown to sensitize tumor tissues to radiation. [ 16 ] The efficacy of EBRT and concurrent low dose CDDP was reported in patients with non-metastatic non-small cell lung cancer: Schaake-Koning et al .,[ 17 ] demonstrated in their large scale randomized study that a combination of EBRT and low dose CDDP produced a significantly higher overall survival rate than that with EBRT alone.…”

Section: Discussionmentioning

confidence: 99%

External beam radiation plus concurrent intra-arterial chemotherapy with low dose cisplatin for muscle invasive bladder cancer

Matsumoto

Samma²,

Fukui³

et al. 2015

Indian J Urol

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Introduction:We aimed to investigate the long-term outcome of trimodality therapy consisting of transurethral resection of bladder tumor, external beam radiation therapy, and concurrent intra-arterial low dose cisplatin for patients with muscle invasive bladder cancer.Materials and Methods:We retrospectively reviewed the medical records of 37 consecutive patients (28 men and 9 women) who underwent trimodality therapy for T2-3N0M0 bladder cancer at our hospital between 1996 and 2011. A total of 60Gy of external beam radiation therapy was administered. A daily low dose of cisplatin was administered intra-arterially through a subcutaneously placed reservoir on the days of radiation therapy. Complete response was defined as no residual cancer in transurethral resection specimens and negative cytology. When a complete response could not be achieved, patients underwent additional intra-arterial chemotherapy.Results:Five-year cause specific, disease free, and overall survival rates were 86.4%, 69.7%, and 69.6%, respectively, with a mean follow-up period of 56.5 ± 6.1 months. Five-year cause specific survivals of the complete response group after the trimodality therapy, the complete response group after additional intra-arterial chemotherapy and the non-complete response group were 100% (n = 21), 85.9% (n = 9) and 0% (n = 7), respectively. Five-year overall survivals of the complete response group after the trimodality therapy, the complete response group after additional intra-arterial chemotherapy and the non-complete response group were 82.8%, 85.3% and 0%, respectively.Conclusions:This trimodality therapy for muscle invasive bladder cancer could achieve favorable survival rates with bladder preservation and minimal adverse events. This trimodality therapy can be one of the useful treatment options.

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The Role of Taxanes in the Management of Bladder Cancer

Cited by 30 publications

References 38 publications

Paclitaxel incorporated in hydrophobically derivatized hyperbranched polyglycerols for intravesical bladder cancer therapy

Paclitaxel incorporated in hydrophobically derivatized hyperbranched polyglycerols for intravesical bladder cancer therapy

Use of oral paclitaxel for the treatment of bladder tumors in dogs

External beam radiation plus concurrent intra-arterial chemotherapy with low dose cisplatin for muscle invasive bladder cancer

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