scholarly journals Physicochemical characteristics of abiraterone acetate used for the treatment of prostate cancer

2016 ◽  
Author(s):  
Marta Łaszcz ◽  
Kinga Trzcińska ◽  
Elżbieta U. Stolarczyk
Keyword(s):  
Prostate Cancer ◽  
Solid State ◽  
Drug Product ◽  
Treatment Options ◽  
Polymorphic Form ◽  
Abiraterone Acetate ◽  
Crystalline Solid ◽  
Castration Resistant Prostate Cancer ◽  
Scanning Calorimetry ◽  
X Ray

Prostate cancer is the most common cancer among men and often has no early symptoms. The major treatment options that include surgical or medical castration cause ablation of the production of testosterone, dihydrotestosterone and related androgens by the testes. These procedures do not affect adrenal, prostate and other tissues androgen production, therefore they are combined with androgen receptor antagonists to block their action. Recent studies have established that in castration-resistant prostate cancer many androgen-regulated genes become re-expressed and tissue androgen levels increase despite low serum levels. Abiraterone acetate inhibits the key enzyme cytochrome P450 17α-hydroxy/17,20-lyase (CYP17) which catalyzes the biosynthesis of androgens and provides the effective treatment of prostate cancer patients. The aim of this work was abiraterone acetate polymorph diagnostics and physcicochemical characteristics of polymorphs. Polymorphism is the ability of a compound in the solid state to exist in different crystalline forms. Molecules, having the same chemical composition, exhibit different spatial arrangements and/or exist in different conformations. Substances that exist in a non-crystalline solid state are said to be amorphous. The term pseudopolymorphism is used to describe solvates (including hydrates). Different polymorphs of a solid compound exhibit distinct physical properties such as, e.g.: hygroscopicity, solubility, dissolution rate, melting point and stability. All of which play a very important role in the pharmaceutical industry. The undesirable polymorphic form with lower solubility and consequently with a lower absorption rate decreases the concentration of active substance in the blood. The Biopharmaceutics Classification System classifies drugs taking into account their solubility. Because a change in a polymorphic form may influence on a drug product affectivity and its toxic properties the regulations required by the ICH Q6A guideline according to the decision tree no 4 demand the control of solid state behavior. Therefore, the polymorphic behavior of abiraterone acetate has to be carefully investigated and all found polymorphs have to be fully characterized. Abiraterone acetate was characterized by following methods: X-ray powder diffraction, infrared and Raman spectroscopy, differential scanning calorimetry. Polymorph screening was performed and single crystals were obtained by a vapour diffusion crystallisation. The structure of abiraterone acetate was solved by the single crystal X-ray diffraction. Additionally the structure was confirmed by the direct sample injection method (DI).

scholarly journals Physicochemical characteristics of abiraterone acetate used for the treatment of prostate cancer

2016 ◽  
Author(s):  
Marta Łaszcz ◽  
Kinga Trzcińska ◽  
Elżbieta U. Stolarczyk
Keyword(s):  
Prostate Cancer ◽  
Solid State ◽  
Drug Product ◽  
Treatment Options ◽  
Polymorphic Form ◽  
Abiraterone Acetate ◽  
Crystalline Solid ◽  
Castration Resistant Prostate Cancer ◽  
Scanning Calorimetry ◽  
X Ray

Prostate cancer is the most common cancer among men and often has no early symptoms. The major treatment options that include surgical or medical castration cause ablation of the production of testosterone, dihydrotestosterone and related androgens by the testes. These procedures do not affect adrenal, prostate and other tissues androgen production, therefore they are combined with androgen receptor antagonists to block their action. Recent studies have established that in castration-resistant prostate cancer many androgen-regulated genes become re-expressed and tissue androgen levels increase despite low serum levels. Abiraterone acetate inhibits the key enzyme cytochrome P450 17α-hydroxy/17,20-lyase (CYP17) which catalyzes the biosynthesis of androgens and provides the effective treatment of prostate cancer patients. The aim of this work was abiraterone acetate polymorph diagnostics and physcicochemical characteristics of polymorphs. Polymorphism is the ability of a compound in the solid state to exist in different crystalline forms. Molecules, having the same chemical composition, exhibit different spatial arrangements and/or exist in different conformations. Substances that exist in a non-crystalline solid state are said to be amorphous. The term pseudopolymorphism is used to describe solvates (including hydrates). Different polymorphs of a solid compound exhibit distinct physical properties such as, e.g.: hygroscopicity, solubility, dissolution rate, melting point and stability. All of which play a very important role in the pharmaceutical industry. The undesirable polymorphic form with lower solubility and consequently with a lower absorption rate decreases the concentration of active substance in the blood. The Biopharmaceutics Classification System classifies drugs taking into account their solubility. Because a change in a polymorphic form may influence on a drug product affectivity and its toxic properties the regulations required by the ICH Q6A guideline according to the decision tree no 4 demand the control of solid state behavior. Therefore, the polymorphic behavior of abiraterone acetate has to be carefully investigated and all found polymorphs have to be fully characterized. Abiraterone acetate was characterized by following methods: X-ray powder diffraction, infrared and Raman spectroscopy, differential scanning calorimetry. Polymorph screening was performed and single crystals were obtained by a vapour diffusion crystallisation. The structure of abiraterone acetate was solved by the single crystal X-ray diffraction. Additionally the structure was confirmed by the direct sample injection method (DI).

scholarly journals KEYNOTE-921: Phase III study of pembrolizumab plus docetaxel for metastatic castration-resistant prostate cancer

2021 ◽  
Author(s):  
Daniel P Petrylak ◽  
Raffaele Ratta ◽  
Rustem Gafanov ◽  
Gaetano Facchini ◽  
Josep M Piulats ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Options ◽  
Unmet Need ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Castration Resistant ◽  
Previously Treated

Despite recent advances, treatment options for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after next-generation hormonal agents (NHAs) are limited and provide only modest survival benefit. Thus, an unmet need remains for mCRPC patients after treatment with targeted endocrine therapy or NHA therapy. Pembrolizumab, a humanized monoclonal antibody for PD-1, has been found to have activity as monotherapy in patients with mCRPC and as combination therapy in a Phase Ib/II study with docetaxel and prednisone/prednisolone for patients previously treated with enzalutamide or abiraterone acetate. The aim of the randomized, double-blind, Phase III KEYNOTE-921 study is to evaluate the efficacy and safety of pembrolizumab plus docetaxel in patients with mCRPC who were previously treated with an NHA. Clinical trial registration: NCT03834506 ( ClinicalTrials.gov )

scholarly journals The investigation of polymorph transition of erlotinib salts

2016 ◽  
Author(s):  
Wioleta Maruszak ◽  
Marta Łaszcz ◽  
Kinga Trzcińska ◽  
Wojciech Łuniewski ◽  
Krzysztof Bańkowski ◽  
...  
Keyword(s):  
Solid State ◽  
Kinase Inhibitor ◽  
Drug Product ◽  
Variable Temperature ◽  
Drug Substance ◽  
Crystalline Solid ◽  
Scanning Calorimetry ◽  
Thermal Methods ◽  
Polymorphic Transitions ◽  
Polymorphic Forms

Erlotinib is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR) and is used to treat non-small cell lung cancer (NSCLC), pancreatic cancer and several other types of cancer [1]. It is known that erlotinib forms different salts which can exist in multiple crystalline solid forms. This important property known as a polymorphism may have an impact on physical and chemical stability of the drug substance (API), processability during manufacturing in the final drug product and bioavailability of the drug to the patient. Changes in the crystal structure of API can lead to the undesired changes in properties. Hence, the control of the polymorphic form is essential during the drug substance manufacture and requires a thorough understanding of solid-state changes that may occur in pharmaceutical materials. To achieve a comprehensive understanding of solid-state transformations different analytical techniques are applied. In our studies the variable–temperature powder X-ray diffraction (VT–PXRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transformed infrared (FTIR), attenuated total reflectance (ATR) and Raman spectroscopy were used to investigate the correlation between the thermal behavior and structural transformations of polymorphic forms of erlotinib salts. VT-PXRD method has detected the temperature range of the existence of polymorphic transitions, spectroscopy methods have characterized intramolecular vibrations and thermal methods have provided information on the transition and melting temperature and relationships between polymorphic forms.

scholarly journals The investigation of polymorph transition of erlotinib salts

2016 ◽  
Author(s):  
Wioleta Maruszak ◽  
Marta Łaszcz ◽  
Kinga Trzcińska ◽  
Wojciech Łuniewski ◽  
Krzysztof Bańkowski ◽  
...  
Keyword(s):  
Solid State ◽  
Kinase Inhibitor ◽  
Drug Product ◽  
Variable Temperature ◽  
Drug Substance ◽  
Crystalline Solid ◽  
Scanning Calorimetry ◽  
Thermal Methods ◽  
Polymorphic Transitions ◽  
Polymorphic Forms

Erlotinib is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR) and is used to treat non-small cell lung cancer (NSCLC), pancreatic cancer and several other types of cancer [1]. It is known that erlotinib forms different salts which can exist in multiple crystalline solid forms. This important property known as a polymorphism may have an impact on physical and chemical stability of the drug substance (API), processability during manufacturing in the final drug product and bioavailability of the drug to the patient. Changes in the crystal structure of API can lead to the undesired changes in properties. Hence, the control of the polymorphic form is essential during the drug substance manufacture and requires a thorough understanding of solid-state changes that may occur in pharmaceutical materials. To achieve a comprehensive understanding of solid-state transformations different analytical techniques are applied. In our studies the variable–temperature powder X-ray diffraction (VT–PXRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transformed infrared (FTIR), attenuated total reflectance (ATR) and Raman spectroscopy were used to investigate the correlation between the thermal behavior and structural transformations of polymorphic forms of erlotinib salts. VT-PXRD method has detected the temperature range of the existence of polymorphic transitions, spectroscopy methods have characterized intramolecular vibrations and thermal methods have provided information on the transition and melting temperature and relationships between polymorphic forms.

Cabazitaxel in the Management of Metastatic Castration-resistant Prostate Cancer Progressing After Docetaxel-based Chemotherapy

2012 ◽  
Vol 08 (01) ◽  
pp. 42 ◽  
Author(s):  
Axel Heidenreich ◽  
David Pfister ◽  
◽  
Keyword(s):  
Prostate Cancer ◽  
Side Effects ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Metastatic Progression ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Patient Counselling ◽  
Castration Resistant

Docetaxel is the guideline-recommended first-line chemotherapy in men with castration-resistant prostate cancer (CRPC). Despite its proven survival benefit, however, all patients will progress after a mean interval of six to eight months. Recently, the FDA approved cabazitaxel and abiraterone acetate as effective second-line treatment options in this clinical scenario. By comparison with mitoxantrone, cabazitaxel improves progression-free survival, overall survival, time to prostate surface antigen (PSA) progression and time to metastatic progression. On the other hand, cabazitaxel (Sanofi) is asscociated with a significantly higher frequency of grade 3 and 4 haematotoxic and gastrointestinal side effects than mitoxantrone. In experienced hands, and with the use of proactive therapeutic measures – such as weekly monitoring, adequate patient counselling and appropriate application of the guidelines on management and prophylaxis of neutropenia and diarrhoea — all side effects can be handled easily without harming the patient, as has been shown recently by the analysis of the results of the German and European compassionate use programmes. Cabazitaxel is one of the key components in the management of disease progression after docetaxel, and might be of benefit in men with high metastatic burden, rapid PSA doubling time and minimal side effects during first-line docetaxel therapy.

scholarly journals Management of Metastatic Castration-resistant Prostate Cancer

2011 ◽  
Vol 07 (04) ◽  
pp. 251
Author(s):  
Emmanuel S Antonarakis ◽  
Keyword(s):  
Prostate Cancer ◽  
Treatment Options ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Delivery Of Care ◽  
Castration Resistant ◽  
Skeletal Related Events ◽  
Confirmatory Trials

The management of men with metastatic castration-resistant prostate cancer (CRPC) has taken several leaps forwards in the last two years, with the demonstration of improved overall survival with three novel agents (sipuleucel-T, cabazitaxel and abiraterone acetate) and a significant delay in skeletal-related events observed with denosumab. The pipeline of systemic therapies in prostate cancer remains strong, as multiple agents with a diverse array of mechanisms of action are demonstrating preliminary signs of clinical benefit, leading to more definitive Phase III confirmatory trials. In this review, we will discuss the evolving landscape of treatment options for men with CRPC, with a particular focus on currently approved and emerging treatment options for these patients. Knowledge of these evolving standards will help to optimise delivery of care and long-term outcomes in men with advanced CRPC.

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