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Benjamin Kearns, Abdullah Pandor, Matt Stevenson, Jean Hamilton, Duncan Chambers, Mark Clowes, John Graham, M Satish Kumar
As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures cabazitaxel (Jevtana(®), Sanofi, UK) to submit evidence for the clinical and cost effectiveness of cabazitaxel for treatment of patients with metastatic hormone-relapsed prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG)...
October 22, 2016: PharmacoEconomics
Eiman Mukhtar, Vaqar M Adhami, Imtiaz A Siddiqui, Ajit K Verma, Hasan Mukhtar
Although treatment of prostate cancer (PCa) has improved over the past several years, taxanes such as cabazitaxel remain the only form of effective chemotherapy that improves survival in patients with metastatic castration-resistant PCa. However, the effectiveness of this class of drugs has been associated with various side effects and drug resistance. We previously reported that fisetin, a hydroxyflavone, is a microtubule stabilizing agent and inhibits PCa cell proliferation, migration, and invasion and suggested its use as an adjuvant for treatment of prostate and other cancer types...
October 7, 2016: Molecular Cancer Therapeutics
Chad R Ritch, Michael S Cookson
Docetaxel based chemotherapy showed survival benefit and emerged as the mainstay of treatment for castration resistant prostate cancer (CRPC) in 2004. However, therapeutic options have expanded rapidly since 2011. The spectrum of new agents is broad and includes drugs that target the androgen axis (enzalutamide, abiraterone), immunotherapy (sipuleucel-T), bone seeking radionuclides (radium-223), and second line chemotherapy (cabazitaxel). In addition, new agents have been developed to reduce skeletal related events (denosumab)...
October 17, 2016: BMJ: British Medical Journal
Zachery R Reichert, Maha Hussain
The development of metastatic castration-resistant prostate cancer (mCRPC) signals the terminal disease phase. The preceding hormone-dependent disease setting is effectively managed with androgen deprivation therapy. This foundation of treatment has a high rate of biochemical and clinical response and meaningful clinical benefit but is finite in duration as most cancers will progress to castration resistance. Historically, treatment for mCRPC entailed androgen receptor (AR) inhibitors (nilutamide, flutamide, bicalutamide), nonspecific steroidal biosynthesis inhibitors (ketoconazole, itraconazole), steroids (prednisone, diethylstilbesterol, dexamethasone), or palliative chemotherapy (mitoxantrone, estramustine), but none of these strategies impacted survival...
September 2016: Cancer Journal
Edel McCrea, Tristan M Sissung, Douglas K Price, Cindy H Chau, William D Figg
Significant therapeutic progress has been made in treating prostate cancer in recent years. Drugs such as enzalutamide, abiraterone, and cabazitaxel have expanded the treatment armamentarium, although it is not completely clear which of these drugs are the most-effective option for individual patients. Moreover, such advances have been tempered by the development of therapeutic resistance. The purpose of this review is to summarize the current literature pertaining to the biochemical effects of AR variants and their consequences on prostate cancer therapies at both the molecular level and in clinical treatment...
October 7, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Vanita Noronha, Amit Joshi, Vamshi Krishna Muddu, Vijay Maruti Patil, Kumar Prabhash
<bold>Objective:</bold> To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) patients from the named patient programme (NPP) at our centre. <bold>Methods:</bold> mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL) changes, and safety were reported...
May 2016: Case Reports in Oncology
Sebastien J Hotte
Despite the significant survival benefit of taxane therapy in metastatic castration-resistant prostate cancer (mCRPC), all patients inevitably develop treatment resistance. An understanding of resistance mechanisms has led to new therapies for prostate cancer (cabazitaxel, abiraterone and enzalutamide), all of which have improved survival following first-line docetaxel. Another treatment, currently in development, targets the prosurvival molecule clusterin. Custirsen, an antisense molecule that inhibits clusterin production, has shown promise in combination with docetaxel in mCRPC patients at risk for poor outcomes...
October 7, 2016: Future Oncology
Annemieke J M Nieuweboer, Anne-Joy M de Graan, Paul Hamberg, Sander Bins, Robert J van Soest, Robbert J van Alphen, Andries M Bergman, Aart Beeker, Henk van Halteren, Albert Ten Tije, Hanneke Zuetenhorst, Nelly van der Meer, Dana Chitu, Ronald de Wit, Ron H J Mathijssen
PURPOSE: Forty-seven percent of patients in the pivotal trial of cabazitaxel reported diarrhea of any grade. Aiming to reduce the incidence of diarrhea, we studied the effects of budesonide on the grade of cabazitaxel-induced diarrhea during the first two treatment cycles. EXPERIMENTAL DESIGN: Between December 2011 and October 2015, 246 metastatic castration resistant prostate cancer patients were randomized to receive standard of care cabazitaxel 25 mg/m2 3-weekly plus prednisone 10 mg/day (group CABA) or same dose/schedule of cabazitaxel with concomitant budesonide 9 mg daily during the first two treatment cycles (group BUD)...
October 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Josef Mang, Konstanze Merkle, Martina Heller, Julia Schüler, Yanis Tolstov, Jielin Li, Markus Hohenfellner, Stefan Duensing
BACKGROUND: Taxanes are routinely used to treat men with advanced prostate cancer, yet their molecular mode of action is poorly characterized. Taxanes stabilize microtubules and may hence interfere with a plethora of cellular processes, most notably mitosis. However, prostate cancer is typically a slowly growing tumor suggesting that additional processes play a role in the response to taxanes. METHODS: Here, we analyzed the potential effect of taxanes on microtubuli-dependent intracellular transport and signaling processes, specifically, nuclear translocation of the androgen receptor and modulation of the RAS-RAF-MEK-ERK signaling cascade...
September 28, 2016: Urologic Oncology
Sayaka Sobue, Naoki Mizutani, Yuka Aoyama, Yoshiyuki Kawamoto, Motoshi Suzuki, Yoshinori Nozawa, Masatoshi Ichihara, Takashi Murate
Paclitaxel (PTX) is a microtubule-targeting drug widely used for the treatment of a variety of cancers. However, drug resistance can emerge after a series of treatments, and this can seriously affect the patient's prognosis. Here, we analyzed the mechanism of PTX resistance using a human prostate cancer cell line, PC3, and its PTX-resistant subline, PC3-PR. Compared with PC3, PC3-PR exhibited some unique phenotypes that might be associated with PTX resistance, including decreased expression of acetylated α-tubulin and the cell cycle regulator p21, and increased expression of βIII tubulin, histone deacetylase 6 (HDAC6), and the anti-apoptotic protein Bcl2...
October 28, 2016: Biochemical and Biophysical Research Communications
Fable Zustovich, Davide Pastorelli
Bone metastases affect the majority of patients with castration-resistant prostate cancer (CRPC), resulting in significant morbidity and mortality. This review describes the current therapies available for the management of CRPC patients with bone metastases. Areas covered: Studies on the use of currently available therapeutic approaches for palliating pain, delaying skeletal-related events (SREs) and prolonging survival in CRPC patients with bone metastases have been examined. PubMed database was searched in May 2016 starting with the following keywords: ('castration-resistant prostate cancer' OR 'CRPC') AND 'bone metastases', and approximately 270 results were retrieved...
October 6, 2016: Expert Review of Anticancer Therapy
Ralf-Dieter Hofheinz, Carsten Lange, Thorsten Ecke, Susanne Kloss, Burkhard Linsse, Christine Windemuth-Kieselbach, Peter Hammerer, Salah-Eddin Al-Batran
OBJECTIVE: To examine health-related quality of life in men with metastatic castration-resistant prostate cancer on cabazitaxel. PATIENTS AND METHODS: Men with metastatic castration-resistant prostate cancer receiving cabazitaxel (25 mg/m², every 3 weeks) and 10 mg/day oral prednis(ol)one were enrolled (2011-2014) in the non-interventional prospective QoLiTime study. Primary outcome was change in quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30 item) with respect to PSA response after 4 cycles of cabazitaxel...
September 12, 2016: BJU International
Xiaowei Tai, Yang Wang, Li Zhang, Yuting Yang, Kairong Shi, Shaobo Ruan, Yayuan Liu, Huile Gao, Zhirong Zhang, Qin He
Cabazitaxel (CBX) is an effective antineoplastic agent for the treatment of many kinds of cancers. However, the poor water solubility remains a serious deterrent to the utilization of CBX as a commercial drug. In this study, we designed a strategy that integrated CBX into albumin nanoparticles (ANs) formed with human serum albumin (HSA) to improve the water solubility and targeting ability. Meanwhile, we utilized a photothermal agent-indocyanine green (ICG), which could cooperate with CBX to enhance the antitumor effect...
October 2, 2016: Journal of Drug Targeting
A Kotsakis, A Matikas, F Koinis, N Kentepozidis, I I Varthalitis, V Karavassilis, Ep Samantas, P Katsaounis, E K Dermitzaki, D Hatzidaki, D Mavroudis, V Georgoulias
BACKGROUND: Cabazitaxel, a semisynthetic microtubule inhibitor, has shown antitumour activity in models resistant to paclitaxel and docetaxel, and it has been approved for the treatment of docetaxel-resistant prostate cancer. We investigated its activity in patients with advanced non-small-cell lung cancer (NSCLC) progressing under or after docetaxel-based regimens. METHODS: Patients with locally advanced unresectable or metastatic NSCLC, with an Eastern Cooperative Oncology Group performance status of 0-2, were enrolled; patients had to have received up to two prior chemotherapy regimens for the treatment of advanced disease, including one docetaxel-containing regimen...
September 27, 2016: British Journal of Cancer
Farah Yassine, Hala Gali-Muhtasib, Elia Salibi
Taxanes are a family of diterpenes produced by the yews (Taxus genus) that are extensively used in chemotherapy. The family encompasses paclitaxel, docetaxel and the recently added cabazitaxel, all of which were proven to be promising anti-cancer drugs. Due to the over harvesting danger threatening the yew trees as well as the many challenges faced by taxane-based chemotherapy, new formulations, analogs and delivery systems are required. Here, we undertook a structured search of the bibliographical database PubMed for peer-reviewed research papers relying on key words and date of publication and organized the information based on the method of taxane drug delivery...
September 7, 2016: Current Medicinal Chemistry
Philip Cornford, Joaquim Bellmunt, Michel Bolla, Erik Briers, Maria De Santis, Tobias Gross, Ann M Henry, Steven Joniau, Thomas B Lam, Malcolm D Mason, Henk G van der Poel, Theo H van der Kwast, Olivier Rouvière, Thomas Wiegel, Nicolas Mottet
OBJECTIVE: To present a summary of the 2016 version of the European Association of Urology (EAU) - European Society for Radiotherapy & Oncology (ESTRO) - International Society of Geriatric Oncology (SIOG) Guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC). EVIDENCE ACQUISITION: The working panel performed a literature review of the new data (2013-2015). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature...
August 31, 2016: European Urology
Ruichao Huo, Lili Wang, Peijuan Liu, Yong Zhao, Caiqin Zhang, Bing Bai, Xueying Liu, Changhong Shi, Sanhua Wei, Hai Zhang
Cabazitaxel has been used to treat castration-resistant prostate cancer since its approval by the US Food and Drug Administration in 2010. However, whether cabazitaxel may inhibit the proliferation of other tissue‑derived cancer cells, and its underlying mechanism, remains unknown. In the present study, the A549 lung adenocarcinoma cancer cell line was exposed to cabazitaxel, in order to investigate its cytotoxic effect and determine the underlying mechanism. The results demonstrated that cabazitaxel was able to induce autophagy in A549 cells, as evidenced by the formation of autophagosomes, upregulated LC3‑II expression and increased LC3 puncta...
October 2016: Molecular Medicine Reports
Na Qu, Robert J Lee, Yating Sun, Guangsheng Cai, Junyang Wang, Mengqiao Wang, Jiahui Lu, Qingfan Meng, Lirong Teng, Di Wang, Lesheng Teng
Cabazitaxel-loaded human serum albumin nanoparticles (Cbz-NPs) were synthesized to overcome vehicle-related toxicity of current clinical formulation of the drug based on Tween-80 (Cbz-Tween). A salting-out method was used for NP synthesis that avoids the use of chlorinated organic solvent and is simpler compared to the methods based on emulsion-solvent evaporation. Cbz-NPs had a narrow particle size distribution, suitable drug loading content (4.9%), and superior blood biocompatibility based on in vitro hemolysis assay...
2016: International Journal of Nanomedicine
Ricardo Fernandes, Sasha Mazzarello, Brian Hutton, Risa Shorr, Mohammed F K Ibrahim, Carmel Jacobs, Michael Ong, Mark Clemons
Taxane acute pain syndrome (TAPS) is characterized by myalgia and arthralgia starting 24 to 48 hours after taxane-based chemotherapy and lasting ≤ 7 days. Little is known about its incidence and predisposing factors in patients with prostate cancer. A systematic review was performed to identify studies reporting the incidence and risk factors for TAPS in patients receiving taxane-based chemotherapy for prostate cancer. Embase, Ovid Medline, and other nonindexed citations were searched from 1947 to July 7, 2015...
July 28, 2016: Clinical Genitourinary Cancer
Sushil K Badrising, Vincent van der Noort, Paul Hamberg, Jules L L M Coenen, Maureen J Aarts, Inge M van Oort, Alfons J M van den Eertwegh, Maartje Los, H Pieter van den Berg, Hans Gelderblom, Suzan Vrijaldenhoven, Emile D Kerver, Theo van Voorthuizen, Igle J de Jong, John B Haanen, Andries M Bergman
OBJECTIVE: To evaluate the efficacy of enzalutamide (Enz) as fourth- or fifth-line treatment in men with metastasized castration-resistant prostate cancer (mCRPC), by analyzing a retrospective cohort of heavily pretreated patients. METHODS: We evaluated toxicity, overall survival (OS), progression-free survival (PFS) and time to prostate-specific antigen (PSA) progression data from 47 CRPC patients treated with fourth- or fifth-line Enz. RESULTS: All patients were treated with docetaxel and abiraterone acetate and 42 patients (89%) with cabazitaxel...
August 20, 2016: Oncology
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