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Home , Mafosfamide, Motretinide

THE MAIN LA USMILLORA 20180000840A1 T RIMA UTARA MALI AN ( 19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2018 / 0000840 A1 Auerbach et al . (43 ) Pub . Date : Jan . 4 , 2018 (54 ) METHODS AND COMPOSITIONS FOR 2011 , now Pat . No. 8 ,822 ,438 , which is a continuation TREATING CANCER of application No . 11/ 844 ,440 , filed on Aug . 24 , 2007 , now abandoned . (71 ) Applicant: Janssen Oncology , Inc. , Los Angeles, (60 ) Provisional application No . 60 / 921, 506 , filed on Aug . CA (US ) 25 , 2006 . @(72 ) Inventors : Alan H . Auerbach , Hermosa Beach , CA (US ) ; Arie S . Belldegrun , Los Publication Classification Angeles, CA (US ); Johann de Bono , (51 ) Int. Ci. London (GB ) A61K 31/ 58 ( 2006 .01 ) A61K 31 /573 ( 2006 .01 ) @(21 ) Appl. No. : 15 /703 , 773 (52 ) U . S . CI. CPC ...... A61K 31/ 58 (2013 .01 ) ; A61K 31/ 573 (22 ) Filed : Sep . 13 , 2017 ( 2013 .01 ) Related U . S. Application Data (57 ) ABSTRACT (63 ) Continuation of application No . 15 /419 ,148 , filed on Methods and compositions for treating cancer are described Jan . 30 , 2017 , now abandoned , which is a continu herein . More particularly , the methods for treating cancer ation of application No. 15 /019 ,353 , filed on Feb . 9 , comprise administering a 17a -hydroxylase /C17 , 20 - lyase 2016 , which is a continuation of application No . inhibitor , such as abiraterone acetate (i . e ., 3ß -acetoxy - 17 14 / 750 , 297 , filed on Jun . 25 , 2015 , now abandoned , ( 3 - pyridyl) androsta - 5 , 16 - diene ) , in combination with at which is a continuation of application No . 14 /485 , least one additional therapeutic agent such as an anti - cancer 083 , filed on Sep . 12 , 2014 , now abandoned , which is agent or a steroid . Furthermore , disclosed are compositions a continuation of application No . 14 / 444 ,513 , filed on comprising a 17a -hydroxylase /C17 , 20 - lyase inhibitor, and at Jul. 28 , 2014 , now abandoned , which is a continua least one additional therapeutic agent, such as an anti - cancer tion of application No . 13 /034 , 340 , filed on Feb . 24 , agent or a steroid . US 2018 / 0000840 A1 Jan . 4 , 2018

METHODS AND COMPOSITIONS FOR may also suffer from relapsing or recurring cancer . Cur TREATING CANCER rently , such refractory cancer patients are left with very few treatment options . FIELD OF THE INVENTION [0007 ] Despite the progress made in the treatment of cancer, there remains a need for more effective ways to treat [ 0001 ] Methods and compositions for treating cancer are cancer such as, but not limited to , prostate cancer and breast described herein . More particularly , the methods for treating cancer. Additionally , there is a need for effective anti - cancer cancer comprise administering a 17a -hydroxylase /C17 treatment options for patients who are not responding to 20 - lyase inhibitor, such as abiraterone acetate ( i . e . , 3ß - ac current anti - cancer treatments . Also , there is a need for etoxy - 17 - ( 3 -pyridyl ) androsta - 5 , 16 -diene ) , in combination effective anti - cancer treatment options for patients whose with at least one additional therapeutic agent, such as an cancer has recurred . anti- cancer agent or a steroid . Furthermore, disclosed are compositions comprising a 17a -hydroxylase /C17 20 - 1yase SUMMARY OF THE INVENTION inhibitor, and at least one additional therapeutic agent such [0008 ] Described herein are methods for treating a cancer as an anti -cancer agent or a steroid , e. g ., a corticosteroid or, in which a therapeutically effective amount of a 17a more specifically , a glucocorticoid . hydroxylase / C , z 20 - lyase inhibitor , such as abiraterone acetate ( i. e . 3ß -acetoxy - 17 -( 3 -pyridyl )androsta -5 , 16 - diene ), BACKGROUND is administered to a patient, e . g ., a patient in need thereof, in combination with a therapeutically effective amount of at [0002 ] The number of people diagnosed with cancer has least one additional therapeutic agent including , but not significantly increased . Of special interest are individuals limited to , an anti -cancer agent or steroid . Such methods can diagnosed with androgen -dependent disorders , such as pros also provide an effective treatment for individuals with a tate cancer , and - dependent disorders , such as breast refractory cancer, including individuals who are currently cancer since such diagnoses are increasing in number at an undergoing a cancer treatment. Therefore , in certain alarming rate . embodiments , the method is directed to treating a refractory [ 0003] Prostate cancer is currently the most common cancer in a patient, in which a therapeutically effective non - skin cancer and the second leading cause of cancer amount of 17a -hydroxylase /C17 , 20 - lyase inhibitor is admin related death in men after lung cancer. The primary course istered to a patient currently receiving an anti - cancer agent. of treatment for patients diagnosed with organ - confined [0009 ] For example , in certain embodiments , the method prostate cancer is usually prostatectomy or radiotherapy . Not for the treatment of a cancer in a mammal comprises only are these treatments highly invasive and have undesir administering an amount of about 0 .01 mg/ kg / day to about able side effects , such localized treatments are not effective 100 mg/ kg /day of abiraterone acetate and an amount of on prostate cancer after it has metastasized . Moreover, a about 0 . 1 mg/ m² to about 20 mg/ m - of . large percent of individuals who receive localized treatments [0010 ] In another embodiment , the method for the treat will suffer from recurring cancer. ment of a cancer in a mammal comprises administering an amount of about 0 .01 mg/ kg / day to about 100 mg/ kg/ day of [0004 ] Additionally , breast cancer incidence in women has abiraterone acetate and an amount of about 1 mg/ m² to about increased from one out of every 20 women in 1960 to one 175 mg/ m - of . out of every eight women in 2005 . Moreover, it is the most [0011 ] In still other embodiments, the method for the common cancer among white and African - American treatment of a cancer in a mammal comprises administering women . Similar to treating prostate cancer , most options for an amount of about 0 . 01 mg/ kg /day to about 100 mg/ kg / day women diagnosed with breast cancer are highly invasive and of abiraterone acetate and an amount of about 1 mg/ m² to have significant side - effects . Such treatments include sur about 100 mg/ m of . gery , radiation and . [ 0012 ] Furthermore , described herein is a method for the [ 0005 ] Hormone therapy is another treatment option for treatmentof a cancer in a mammal comprising administering individuals diagnosed with prostate or breast cancer. Hor an amount of about 0 . 01 mg/ kg /day to about 100 mg/ kg / day mone therapy is a form of systemic treatment for prostate or of abiraterone acetate ; and an amount of about 0 . 01 mg to breast cancer wherein hormone ablation agents are used to about 200 mg of leuprolide , wherein the leuprolide is suppress the production or block the effects of hormones, administered over a period of about 3 days to about 12 such as estrogen and progesterone in the body , which are months. believed to promote the growth of breast cancer, as well as [0013 ]. In other embodiments , themethod for the treatment testosterone and dihydrotestosterone , which are believed to of a cancer in a mammal comprises administering an amount promote the growth of prostate cancer. Moreover, hormone of about 0 .01 mg/ kg / day to about 100 mg/kg / day of abi therapy is less invasive than surgery and does not have many raterone acetate and an amount of about 0 .01 mg to about 20 of the side effects associated with chemotherapy or radia mg of goserelin , wherein the goserelin is administered over tion . Hormone therapy can also be used by itself or in a period of about 28 days to about 3 months . addition to localized therapy and has shown to be effective [0014 ] Additionally , in another embodiment, the method in individuals whose cancer has metastasized . for the treatment of a cancer in a mammal comprises [ 0006 ] Even though hormone therapy is less invasive and administering an amount of about 0 .01 mg/ kg / day to about can be used on more advanced stages of cancer, some 100 mg/ kg /day of abiraterone acetate and an amount of individuals administered current hormone therapy treat about 0 .01 mg to about 20 mg of triptorelin , wherein the ments may not show a significant response or may not show triptorelin is administered over a period of about 1 month . any response at all to such treatments . Additionally , some [0015 ] The method for the treatment of a cancer in a patients treated with current hormone therapy treatments mammal can also comprise administering an amount of US 2018 / 0000840 A1 Jan . 4 , 2018 about 0 .01 mg/ kg /day to about 100 mg/ kg /day of abiraterone pig . In one embodiment , the patient is a mammal and in acetate and an amount of about 0 . 1 ug /day to about 500 another embodiment the patient is a human . In certain ug /day of seocalcitol, such as about 100 ug /day of seocal embodiments, the patient can be an adult male or female . In citol . some embodiments , the patient is a male of age about 30 [ 0016 ] Also , the method for the treatment of a cancer in a years to about 85 years . In other embodiments , the patient is mammal can comprise administering an amount of about a female of age about 30 years to about 85 years . In a 0 .01 mg/ kg /day to about 100 mg/ kg /day of abiraterone particular embodiment, the patient has or is susceptible to acetate and an amount of about 1 mg/ day to about 300 having ( e . g . , through genetic or environmental factors ) can mg/ day of . cer. In a further embodiment, the patient has or is susceptible [ 0017 In yet another embodiment, the method for the to having ( e . g . , through genetic or environmental factors ) a treatment of a cancer in a mammal can comprise adminis tumor. In other embodiments , the patient can be castrated or tering an amount of about 0 .01 mg /kg / day to about 100 non - castrated . mg/ kg / day of abiraterone acetate and an amount of about 1 [0024 ] The term “ 17a -hydroxylase /C17 , 20 - lyase inhibi mg/ day to about 2000 mg/ day of . tor” as used herein refers to an inhibitor of 17a -hydroxylase ! [0018 ] Moreover , the method for the treatment of a cancer C12 . 20 - lyase , (which is an enzyme in testosterone synthesis ) , in a mammal can comprise administering an amount of an analog thereof, derivative thereof, metabolite thereof or about 50 mg/ day to about 2000 mg/ day of abiraterone pharmaceutically acceptable salt thereof. Also , unless oth acetate and an amount of about 0 .01 mg/ day to about 500 erwise noted , reference to a particular 17a -hydroxylase /C17 mg /day of a glucocorticoid including , but not limited to , 20 - lyase inhibitor can include analogs , derivatives , metabo hydrocortisone, prednisone or dexamethasone . lites or pharmaceutically acceptable salts of such particular [ 0019 ] Also described herein are compositions for the 17a -hydroxylase / C17. 20 - lyase inhibitor . treatment of cancer that comprise a combination of a thera 10025 ]. The term “ anti - cancer agent” as used herein refers peutically effective amount of at least one 17a -hydroxylase ! to any therapeutic agent that directly or indirectly kills C17. 20 -lyase inhibitor and a therapeutically effective amount cancer cells or directly or indirectly prohibits stops or of at least one additional anti - cancer agent, such as, but not reduces the proliferation of cancer cells . It should be noted limited to , mitoxantrone , paclitaxel, docetaxel , leuprolide , that even though throughout this specification and in the goserelin , triptorelin , seocalcitol, bicalutamide , flutamide, or claims the phrase " anti - cancer agent” is written as a singular a steroid including , but not limited to , hydrocortisone , noun , for example ; " an anti - cancer agent” or “ the anti prednisone , or dexamethasone . cancer agent, ” the phrase " anti- cancer agent ” should not be [ 0020 ] Finally, single unit dosage forms comprising abi interpreted as being limited to the inclusion of a single raterone acetate and a glucocorticoid , optionally with carri anti- cancer agent . ers, diluents or excipients , are contemplated . Also , kits [0026 ] As used herein , and unless otherwise defined , the comprising at least one 17a -hydroxylase /C17 . 20 - lyase phrase " therapeutically effective amount" when used in inhibitor and an additional anti cancer agent or steroid are connection with a 17a -hydroxylase /C17 . 20 - lyase inhibitor or contemplated . For example , the kit may include a vial therapeutic agent means an amount of the 17a - hydroxylasel containing abiraterone acetate and another vial containing a C17 , 20 - lyase inhibitor or therapeutic agent effective for glucocorticoid . treating a disease or disorder disclosed herein , such as cancer . Definitions [0027 ] As used herein and unless otherwise defined the [0021 ] As used herein and unless otherwise defined the phrase " refractory cancer , ” means cancer that is not respond word “ cancer , ” refers to the growth , division or proliferation ing to an anti -cancer treatment or cancer that is not respond of abnormal cells in the body. Cancers that can be treated ing sufficiently to an anti - cancer treatment . Refractory can with the methods and the compositions described herein cer can also include recurring or relapsing cancer . include , but are not limited to , prostate cancer , breast cancer , 0028 ] As used herein and unless otherwise defined the adrenal cancer, leukemia , lymphoma , myeloma, Walden phrase " refractory patient, ” means a patient who has refrac ström ' s macroglobulinemia , monoclonal gammopathy, tory cancer. benign monoclonal gammopathy , heavy chain disease , bone [ 0029 ] As used herein and unless otherwise defined the and connective tissue sarcoma, brain tumors , thyroid cancer , phrase “ relapse cancer, ” means cancer that was at one time pancreatic cancer , pituitary cancer , eye cancer , vaginal can responsive to an anti - cancer treatment but has become no cer, vulvar cancer, cervical cancer , uterine cancer, ovarian longer responsive to such treatment or is no longer respond cancer, esophageal cancer, stomach cancer, colon cancer, ing sufficiently to such treatment. rectal cancer, liver cancer, gallbladder cancer , cholangiocar [0030 ] As used herein and unless otherwise defined the cinoma, lung cancer, testicular cancer, penal cancer, oral phrase “ recurring cancer, ” means cancer that has returned cancer , skin cancer, kidney cancers , Wilms' tumor and after a patient has been earlier diagnosed with cancer , under bladder cancer . gone treatment or had been previously diagnosed as cancer [ 0022 ] As used herein , and unless otherwise defined , the free . terms " treat, ” “ treating " and " treatment” include the eradi [0031 ] As used herein and unless otherwise defined the cation , removal, modification , management or control of a term “ derivative ” refers to a chemically modified compound tumor or primary , regional, or metastatic cancer cells or wherein the chemical modification takes place at one or tissue and the minimization or delay of the spread of cancer. more functional groups of the compound . The derivative [0023 ] As used herein , and unless otherwise defined , the may retain or improve the pharmacological activity of the term " patient” means an animal, including but not limited to compound from which it is derived . an animal such as a human , monkey , cow , horse, sheep , pig , [0032 ] As used herein and unless otherwise defined the chicken , turkey, quail, cat, dog, mouse , rat, rabbit , or guinea term “ analog ” refers to a chemical compound that is struc US 2018 / 0000840 A1 Jan . 4 , 2018

turally similar to another but differs slightly in composition 3a - trifiuoromethyl - 17 - ( 3 -pyridyl ) androst- 16 - en - 3ß - olor ( as in the replacement of one atom by an atom of a different their acid addition salts and 3 - esters as well as metabolites , element or in the presence of a particular functional group ) . analogs, derivatives or a pharmaceutically acceptable salt [ 0033] As used herein and unless otherwise defined the phrase " pharmaceutically acceptable salt ” refers to any salt thereof. of a 17a - hydroxylase/ C17 , 20 - lyase inhibitor which retains [0037 ] In certain embodiments , the 17a -hydroxylase /C17 , the biological effectiveness of the 17a -hydroxylase /C17 , 20 - lyase inhibitor can have the structure of formula ( I) : 20 - lyase inhibitor. Examples of pharmaceutically acceptable salts include , but are not limited to , acetates, sulfates , pyrosulfates , bisulfates, sulfites , bisulfites, phosphates , monohydrogenphosphates , dihydrogenphosphates, meta phosphates , pyrophosphates , chlorides , bromides , iodides , acetates , propionates , decanoates , caprylates, acrylates, for mates, isobutyrates , caproates , heptanoates , propiolates , R16 oxalates , malonates , succinates , suberates, sebacates , fumar ates , maleates , butyne - 1 , 4 - dioates , hexyne - 1 ,6 - dioates, ben RIS zoates , chlorobenzoates , methylbenzoates , dinitrobenzoates , hydroxybenzoates, methoxybenzoates, phthalates , sul R14 R15 fonates , xylenesulfonates, phylacetates, phenylpropionates, phenylbutyrates , citrates, lactates, gamma- hydroxybu wherein X represents the residue of the A , B and C rings of tyrates , glycollates , tartarates , alkanesulfonates ( e . g . meth a steroid which can be, without limitation , androstan -3a - or ane - sulfonate ormesylate ), propanesulfonates, naphthalene 3ß - ol; androst - 5 - en -3a - or 3B - ol; androst- 4 -en - 3 -one ; 1 - sulfonates , naphthalene - 2 - sulfonates , and mandelates . androst- 2 - ene; androst - 4 - ene; androst - 5 -ene ; androsta - 5 , 7 Several of the officially approved salts are listed in Rem dien -3a or 3ß -ol ; androsta - 1 ,4 -dien - 3 -one ; androsta -3 , 5 ington : The Science and Practice of Pharmacy ,Mack Publ. diene ; androsta - 3 ,5 - diene - 3 -ol ; estra -1 , 3, 5 [ 10 ]- triene ; estra Co . , Easton . 1 , 3, 5 [ 10 ] - trien -3 -ol ; 5a - androstan -3 -one ; androst- 4 -ene - 3 , 11 -dione ; 6 - fluoroandrost -4 -ene - 3 -one ; or androstan -4 - ene DETAILED DESCRIPTION OF THE 3 , 6 - dione ; each of which , where structurally permissible , INVENTION can be further derivatized in one or more of the following [0034 ] The methods described herein for treating cancer ways , including, but not limited to , to form 3 - esters ; to have comprise administering to a mammal, preferably a human , a one or more carbon or carbon ring double bonds in any of 17a -hydroxylase /C17 , 20 - lyase inhibitor in addition to at the 5 ,6 -, 6 ,7 -, 7 , 8 - , 9 , 11 - and 11, 12 - positions; as 3 - oximes; least one therapeutic agent, such as an anti -cancer agent or as 3 -methylenes ; as 3 - carboxylates ; as 3 - nitriles; as 3 - nitros ; steroid , particularly a glucocorticoid . The compositions as 3 -desoxy derivatives; to have one or more hydroxy, halo , described herein comprise a 17a -hydroxylase /C17 , 20 - lyase C1- 4 -alkyl , trifluoro -methyl , C1-4 -alkoxy , C1-4 -alkanoyloxy , inhibitor and at least one additional therapeutic agent, such benzoyloxy, oxo , methylene or alkenyl substituents in the A , as an anti -cancer agent or steroid , particularly a corticoster B , or C - ring ; or to be 19 -nor ; oid or glucocorticoid . Other anti- cancer treatments such as, [ 0038 ] R represents a hydrogen atom or an alkyl group of administration of yet another anti -cancer agent, radio therapy, chemotherapy , , surgery or 1 - 4 carbon atoms; other immunotherapy , can be used with the methods and [ 0039 ] R14 represents a hydrogen atom , a halogen atom or compositions . an alkyl group of 1 to 4 carbon atoms; 17a - hydroxylase /C17 , 20 - lyase Inhibitors [0040 ] each of the R15 substituents independently repre [ 0035 ] 17a -hydroxylase / C17, 20 - lyase inhibitors have been sents a hydrogen atom or an alkyl or alkoxy group of 1 - 4 shown to be useful in the treatment of cancer , specifically carbon atoms, a hydroxy group or an alkylcarbonyloxy hormone -dependent disorders such as, androgen - dependent group of 2 to 5 carbon atoms or together represent an oxo or and estrogen - dependent disorders like prostate cancer and methylene group or R14 and one of the RS groups together breast cancer respectively , as described in U . S . Pat. No. represent a double bond and the other Ris group represents 5 ,604 ,213 to Barrie et al. , which is herein incorporated by a hydrogen atom or an alkyl group of 1 to 4 carbon atoms; reference in its entirety. and [ 0036 ] In certain embodiments , the 17a - hydroxylase/ C17, 20 - lyase inhibitor can be 17 - ( 3 -pyridyl ) androsta - 5 , 16 - dien [0041 ] R16 represents a hydrogen atom , halogen atom , or an alkyl group of 1 to 4 carbon atoms, in the form of the free 3B - ol; 17 -( 3 - pyridyl) androsta - 3 ,5 , 16 - triene; 17 -( 3 - pyridyl) bases or pharmaceutically acceptable acid addition salts , but androsta - 4 , 16 - dien - 3 -one ; 17 -( 3 -pyridyl ) estra - 1 , 3 , 5 [ 10 ], 16 excluding 3B -acetoxy - 17 - ( 3 -pyridyl ) androsta - 5 , 14 , 16 tetraen -3 - ol; 17 -( 3 -pyridyl ) - 5a -androst - 16 -en - 3a -ol ; 17 -( 3 triene, 33 , 15a - and 38 ,15B - diacetoxy - 17 - ( 3 -pyridyl ) an pyridyl) -5a -androst - 16 -en - 3 -one ; 17 - ( 3 - pyridyl ) - androsta drosta - 5 , 16 - diene and 3B -methoxy - 17 - ( 3 -pyridyl - 5a - an 4 , 16 -diene - 3 ,11 -dione ; 17 -( 3 -pyridyl ) - androsta - 3 ,5 ,16 drost - 16 - ene. Suitable inhibitors also include metabolites , trien -3 -ol ; 6a - and 6ß -fluoro - 17 -( 3 -pyridyl )androsta -4 , 16 derivatives, analogs , or pharmaceutically acceptable salts of dien - 3 -one 17 -( 3 -pyridyl ) androsta - 4 , 16 -dien - 3 ,6 -dione ; formula (I ) . US 2018 / 0000840 A1 Jan . 4 , 2018

[0042 ] In another embodiment, the 17a -hydroxylase / C17 . [ 0046 ] The 17a - hydroxylase /C17 , 20 - lyase inhibitors can 20 - lyase inhibitor can have the structure of formula ( I ) : be made according to any method known to one skilled in the art. For example, such inhibitors can be synthesized according to the method disclosed in U . S . Pat. Nos. 5 ,604 , 213 and 5 ,618 , 807 to Barrie et al. , herein incorporated by reference . Another method of making 17a -hydroxylase / C17, 20 - lyase inhibitors is disclosed in U . S . provisional applica tion 60 /603 ,558 to Bury , herein incorporated by reference . [0047 ] The amount of 17a -hydroxylase /C17 20 -1yase inhibitor administered to a mammal having cancer is an amount that is sufficient to treat the cancer, whether the 17a -hydroxylase / C17 , 20 - lyase inhibitor is administered alone or in combination with an additional anti- cancer RO treatment, such as an additional anti -cancer agent. wherein R represents hydrogen or a lower acyl group having Additional Therapeutic Agents 1 to 4 carbons. Suitable inhibitors also include derivatives, [0048 ] Suitable compounds that can be used in addition to analogs, or pharmaceutically acceptable salts of formula ( I ) . 17a -hydroxylase / C , 20 - lyase inhibitors as an anti - cancer 10043] In still another embodiment, the 17a - hydroxylase ! agent include , but are not limited to , hormone ablation C17 , 20 - lyase inhibitor can be a 3B - alkanoyloxy - 17 -( 3 agents , anti -androgen agents , differentiating agents , anti pyridyl) androsta - 5 , 16 - diene in which the alkanoyloxy neoplastic agents , kinase inhibitors , anti -metabolite agents , group has from 2 to 4 carbon atoms. alkylating agents , agents , immunological agents , [ 0044 ] In a preferred embodiment, the 17a -hydroxylasel interferon - type agents , intercalating agents , growth factor C17, 20 - lyase inhibitor comprises abiraterone acetate or inhibitors , inhibitors, enzymes, topoisomerase 3B - acetoxy - 17- ( 3 -pyridyl ) androsta -5 , 16 -diene which has inhibitors, biological response modifiers , mitotic inhibitors , the following structural formula : matrix metalloprotease inhibitors, genetic therapeutics , and anti -androgens . The amount of the additional anti - cancer (II ) agent administered to a mammal having cancer is an amount that is sufficient to treat the cancer whether administered alone or in combination with a 17a - hydroxylase/ C17 20 - lyase inhibitor . Below are lists of examples of some of the above classes of anti -cancer agents . The examples are not all inclusive and are for purposes of illustration and not for purposes of limitation . Many of the examples below could be listed in multiple classes of anti -cancer agents and are not restricted in any way to the class in which they are listed in . (0049 ) Suitable hormonal ablation agents include, but are Aco not limited to , androgen ablation agents and estrogen abla tion agents . In preferred embodiments , the 17a -hydroxy lase /C17 . 20 - lyase inhibitor is administered with a hormonal and pharmaceutically acceptable salts thereof. ablation agent, such as deslorelin , leuprolide , goserelin or [0045 ] Preferred salts of abiraterone acetate and methods triptorelin . Even though throughout this specification and in of making such salts are also disclosed in U .S . Provisional the claims the phrase " hormonal ablation agent” is written as Application No. 60 /603 , 559 to Hunt, which is incorporated a singular noun , for example ; “ a hormonal ablation agent ” or by reference in its entirety. Preferred salts include , but are “ the hormonal ablation agent, " the phrase " hormonal abla not limited to , acetates , citrates, lactates , alkanesulfonates tion agent" should not be interpreted as being limited to the ( e . g . methane- sulfonate or mesylate ) and tartarates . Of spe inclusion of a single hormonal ablation agent . The amount of cial interest is the abiraterone acetate mesylate salt ( i. e . the hormonal ablation agent administered to a mammal 3B -acetoxy - 17 - ( 3 - pyridyl) androsta - 5 , 16 - diene mesylate having cancer is an amount that is sufficient to treat the salt ) which has the following structural formula : cancer whether administered alone or in combination with a 17a -hydroxylase /C17 . 20 - lyase inhibitor . [0050 ] Suitable anti -androgen agents include but are not limited to bicalutamide , flutamide and nilutamide. The amount of the anti - androgen agent administered to a mam mal having cancer is an amount that is sufficient to treat the cancer whether administered alone or in combination with a 17a -hydroxylase / C17 , 20 - lyase inhibitor. [ 0051 ] In another embodiment, the 17a -hydroxylase / C17 , 20 - lyase inhibitor may be administered with a differentiating agent. Suitable differentiating agents include , but are not limited to , polyamine inhibitors ; vitamin D and its analogs , such as , calcitriol, doxercalciferol and seocalcitol; metabo lites of vitamin A , such as , ATRA , retinoic acid , ; ectos short - chain fatty acids ; phenylbutyrate ; and nonsteroidal US 2018 / 0000840 A1 Jan . 4 , 2018

anti - inflammatory agents . The amount of the differentiating [0055 ] In another embodiment, the 17a -hydroxylase / C17 . agent administered to a mammal having cancer is an amount 20 -lyase inhibitor may be administered with an alkylating that is sufficient to treat the cancer whether administered agent. Suitable alkylating agents may be selected from , but alone or in combination with a 17a - hydroxylase /C17 . not limited to , aldo - phosphamide analogues , , 20 - lyase inhibitorbilor. anaxirone, bestrabucil, budotitane, , , [ 0052 ] In another preferred embodiment, the 17a -hy , , , cyplatate , droxylase /C17 , 20 - lyase inhibitor may be administered with diphenylspiromustine, diplatinum cytostatic , elmustine , an anti- neoplastic agent, including , but not limited to , tubu sodium , , hepsul- fam , lin interacting agents , topoisomerase inhibitors and agents , , iproplatin , ,mafosfamide , mitolactol, acitretin , alstonine , amonafide, amphethinile , , , , , , spiro ankinomycin , anti- neoplaston , aphidicolin glycinate, aspara mustine, tauromustine , , teroxirone , tetrapla ginase, baccharin , batracylin , benfluron , benzotript, bromo tin and trimelamol. The amount of the alkylating agent fosfamide , caracemide, carmethizole hydrochloride , administered to a mammal having cancer is an amount that chlorsulfaquinoxalone , clanfenur, claviridenone , crisnatol, is sufficient to treat the cancer whether administered alone or curaderm , , cytocytin , , datellip in combination with a 17a -hydroxylase /C17 , 20- lyase inhibi tinium , dihaematoporphyrin ether , dihydrolenperone, dina tor . line, distamycin , docetaxel, elliprabin , elliptinium acetate , [0056 ] In another preferred embodiment, the 17a -hy , ergotamine , , etretinate , fenretinide , droxylase / C17 . 20 -lyase inhibitor may be administered with gallium nitrate , genkwadaphnin , hexadecylphosphocholine , an antibiotic agent . Suitable antibiotic agents may be homoharringtonine , hydroxyurea, ilmofosine , isoglutamine , selected from , but not limited to , , actinomycin , leukoregulin , , merbarone , merocya D , actinoplanone, adriamycin , aeroplysinin derivative , nlne derivatives , methylanilinoacridine , minactivin , mitona , , azino -mycin - A , bisucaberin , bleo fide , mitoquidone , mitoxantrone , mopidamol, motretinide , mycin sulfate , bryostatin - 1 , calichemycin , chromoximycin , N -( retinoyl) amino acids, N -acylated -dehydroalanines , , , ditrisarubicin B , dexametha nafazatrom , nocodazole derivative , ocreotide, oquizanocinc , sone , , doxorubicin - fibrinogen , elsamicin - A , paclitaxel , pancratistatin , pazelliptine , piroxantrone , poly , erbstatin , esorubicin , esperamicin - Al, esperami haematoporphyrin , polypreic acid , probimane, procarba cin - Alb , fostriecin , glidobactin , gregatin - A , grincamycin , zine, proglumide, razoxane, retelliptine, spatol, spirocyclo herbimycin , corticosteroids such as hydrocortisone , idaru propane derivatives , spirogermanium , strypoldinone , bicin , illudins, kazusamycin , kesarirhodins , menogaril, superoxide dismutase , , thaliblastine , tocotrienol, mitomycin , neoenactin , oxalysine , oxaunomycin , peplomy , ukrain , sulfate , , , cin , pilatin , , porothramycin , prednisone, predni vinestramide , , vintriptol, vinzolidine , and witha solone , pyrindanycin A , rapamycin , rhizoxin , rodorubicin , nolides . The amount of the anti -neoplastic agent adminis sibanomicin , siwenmycin , sorangicin - A , sparsomycin , tal tered to a mammal having cancer is an amount that is isomycin , terpentecin , thrazine , tricrozarin A , and . sufficient to treat the cancer whether administered alone or The amount of the antibiotic agent administered to a mam in combination with a 17a -hydroxylase /C17 , 20 - lyase inhibi mal having cancer is an amount that is sufficient to treat the tor. cancer whether administered alone or in combination with a [ 0053 ] The 17a -hydroxylase / C17, 20 -lyase inhibitors may 17a -hydroxylase /C17 ,20 -lyase inhibitor. also be used with a kinase inhibitor including p38 inhibitors [0057 ] Alternatively, the 17a -hydroxylase /C17 , 20 -lyase and CDK inhibitors , TNF inhibitors, metallomatrix pro inhibitors may also be used with other anti- cancer agents , teases inhibitors (MMP ) , COX - 2 inhibitors including cele including but not limited to , acemannan , aclarubicin , coxib , rofecoxib , parecoxib , valdecoxib , and etoricoxib , aldesleukin , alemtuzumab , , altretamine , ami SOD mimics or a , b , inhibitors . The amount of the kinase fostine , amsacrine , , anastrozole, ancestim , bex inhibitor administered to a mammal having cancer is an arotene , broxuridine , , celmoleukin , cetrorelix , amount that is sufficient to treat the cancer whether admin , clotrimazole , daclizumab , dexrazoxane , dilazep , istered alone or in combination with a 17a - hydroxylase / C , 2 . docosanol, , bromocriptine, carmustine , cytara 20 -lyase inhibitor. bine , diclofenac , edelfosine , edrecolomab , eflornithine , [0054 ] In another embodiment , the 17a -hydroxylase / C17 , emitefur, exemestane , exisulind , fadrozole , filgrastim , fin 20 - lyase inhibitor may be administered with an anti -metabo asteride , phosphate , formestane , fotemustine , lite agent. Suitable anti -metabolite agents may be selected gallium nitrate, , glycopine , heptaplatin , iban from , but not limited to , 5 - FU - fibrinogen , acanthifolic acid , dronic acid , imiquimod , iobenguane , , irsogladine , aminothiadiazole , brequinar sodium , , cyclopentyl lanreotide , leflunomide, lenograstim , lentinan sulfate , letro cytosine, cytarabine phosphate stearate , cytarabine conju zole , liarozole , lobaplatin , lonidamine , , melar gates , dezaguanine , dideoxycytidine , dideoxyguanosine , soprol , metoclopramide , mifepristone, miltefosine , miri didox , doxifluridine , fazarabine , , fludarabine mostim , , mitolactol, molgramostim , nafarelin , phosphate , 5 - , N - ( 2 ' - furanidyl) - 5 - fluorouracil , nartograstim , , nilutamide , noscapine , oprelvekin , isopropyl pyrrolizine , methobenzaprim , , nor osaterone, oxaliplatin , pamidronic acid , , pen spermidine , , piritrexim , , thiogua tosan polysulfate sodium , pentostatin , picibanil , pirarubicin , nine , , trimetrexate , tyrosine kinase inhibitors , and , raloxifene , , rasburicase , ritux uricytin . The amount of the anti -metabolite agent adminis imab , romurtide , sargramostim , sizofiran , sobuzoxane , son tered to a mammal having cancer is an amount that is ermin , suramin , tasonermin , , , , sufficient to treat the cancer whether administered alone or temozolomide, teniposide , tetrachlorodecaoxide , thalido in combination with a 17a -hydroxylase /C17 , 20 -lyase inhibi mide , thymalfasin , thyrotropin alfa , topotecan , toremifene , tor. trastuzumab , , , trilostane, trimetrexate , US 2018 / 0000840 A1 Jan . 4 , 2018 ubenimex , , , vinorelbine. The amount ably pharmaceutically suitable for administration . More of the anti- cancer agent administered to a mammal having over, the 17a - hydroxylase / C17, 20 - lyase inhibitor and the cancer is an amount that is sufficient to treat the cancer therapeutic agent, if administered separately , can be admin whether administered alone or in combination with a 17a istered by the same or different modes of administration . hydroxylase /C17 , 20 - lyase inhibitor . Examples of modes of administration include parenteral [0058 ] The 17a -hydroxylase / C17 , 20 - lyase inhibitors may ( e . g ., subcutaneous , intramuscular, intraorbital, intracapsu also be administered or combined with steroids , such as lar, intraspinal, intrasternal , intravenous, intradermal , intra corticosteroids or glucocorticoids . The 17a -hydroxylase ! peritoneal, intraportal, intra - arterial, intrathecal , transmu C17, 20 -lyase inhibitors and the steroid may be administered cosal, intra - articular , and intrapleural, ), transdermal ( e . g ., in the same or in different compositions . Non - limiting topical ) , epidural , and mucosal ( e . g ., intranasal) injection or examples of suitable steroids include hydrocortisone, pred infusion , as well as oral, inhalation , pulmonary , and rectal nisone, or dexamethasone . The amount of the steroid admin administration . In specific embodiments , both are oral . istered to a mammal having cancer is an amount that is [0064 ] For example , the 17a -hydroxylase /C17 , 20 - lyase sufficient to treat the cancer whether administered alone or inhibitor can be administered transdermally and the addi in combination with a 17a -hydroxylase /C17 , 20- lyase inhibi tional therapeutic agent can be administered parenterally . tor. Alternatively , the 17a -hydroxylase / C17, 20 -1yase inhibitor [0059 ] In one embodiment, provided herein are methods can be administered orally , such as in a tablet, caplet or and compositions comprising both abiraterone acetate and a capsule, while the additional therapeutic agent can be steroid particularly a corticosteroid , or more particularly a administered intravenously . Such intravenous administered glucocorticoid . Steroids within the scope of the disclosure therapeutic agents include , but are not limited to , docetaxel include , but are not limited to , ( 1 ) hydrocortisone ( cortisol; injections , such as Taxotere® ; paclitaxel injections , such as cyprionate ( e . g . , CORTEF ) , oral; sodium phosphate injec Paclitaxel® and mitoxantrone injections , such as Novan tion (HYDROCORTONE PHOSPHATE ) ; sodium succinate trone . Also , the additional therapeutic agent can be in the ( e . g ., A - HYDROCORT, Solu -CORTEF ); cortisone acetate form of depots or implants such as leuprolide depots and oral or injection forms, etc . ), (2 ) dexamethasone ( e .g ., implants , e . g. Viadur® and Lupron Depot® ; triptorelin Decadron , oral; Decadron -LA injection , etc . ) , ( 3 ) predniso depots , e . g. Trelstar® ; goserelin implants , e . g. Zoladex® . lone ( e . g . , Delta - CORTEF , prednisolone acetate ( ECONO [ 0065 ] The suitable daily dosage of the 17a - hydroxylase ! PRED ), prednisolone sodium phosphate (HYDELTRA C17 . 20 -lyase inhibitor depends upon a number of factors , SOL ), prednisolone tebutate (HYDELTRA - TBA , etc .) ), or including , the nature of the severity of the condition to be ( 4 ) prednisone DELTASONE , etc . ) and combinations treated , the particular inhibitor, the route of administration thereof. See , e . g . , GOODMAN & GILMAN ' S THE PHARMACOLOGI and the age, weight, and response of the individual patient. CAL BASIS OF THERAPEUTICS , 107H EDITION 2001 . Suitable daily dosages of 17a -hydroxylase / C17, 20 - 1yase [0060 ] In a specific embodiment, single unit solid oral inhibitors can generally range from about 0 .0001 mg/ kg / day dosage forms which comprise an amount from about 50 mg to about 1000 mg/ kg / day , or from about 0 .001 mg/ kg / day to to about 300 mg of abiraterone acetate and an amount from about 200 mg/ kg / day , or from about 0 .01 mg/ kg / day to about 0 .5 mg to about 3 .0 mg of a steroid , e . g . , glucocorti about 200 mg/kg / day, or from about 0 .01 mg/ kg /day to coid in a single composition , optionally with excipients , about 100 mg /kg /day in single or multiple doses . carriers , diluents , etc . is contemplated . For instance , the [0066 ] In some embodiments , the 17a - hydroxylase /C17 , single unit dosage form can comprise about 250 mg of 20 - lyase inhibitor can be administered in an amount from abiraterone acetate and about 1 . 0 mg, 1 . 25 mg, 1 . 5 mg, or about 0 .004 mg/ day to about 5 ,000 mg/ day, or from about 2 . 0 mg of a steroid , such as but not limited to corticosteroids 0 .04 mg/ day to about 3 , 000 mg/ day , or from about 0 . 4 or glucocorticoids. mg/ day to about 1500 mg /day . In certain embodiments , the Administration of the 17a -hydroxylase / C17. 20 - lyase Inhibi 17a -hydroxylase / C17 , 20- lyase inhibitor can be administered tor and an Additional Therapeutic Agent in an amount from about 0 . 1 mg/ day to about 2000 mg/ day [ 0061] The 17a -hydroxylase / C17 , 20 - lyase inhibitor and or from about 1 mg/ day to about 2000 mg/ day or from about the additional therapeutic agent, such as an anti -cancer agent 50 mg/ day to about 2000 mg/ day or from about 100 mg/ day or a steroid can be administered by any method known to to about 1500 mg/ day or from about 5 mg/ day to about 1 ,000 one skilled in the art . In certain embodiments , the 17a mg/ day or from about 5 mg/ day to about 900 mg/ day or from hydroxylase /C17 , 20 - lyase inhibitor and the additional thera about 10 mg/ day to about 800 mg/ day or from about 15 peutic agent can be in separate compositions prior to admin mg/ day to about 700 mg /day or from about 20 mg /day to istration . In the alternative , the 17a - hydroxylase / C , 2 . about 600 mg /day or from about 25 mg /day to about 500 20 -lyase inhibitor and the additional therapeutic agent can be mg/ day in single or multiple doses . combined into a single composition for administration . [0067 ] In certain embodiments , the 17a -hydroxylase /C17 , [ 0062 ] The 17a -hydroxylase / C17 , 20 - lyase inhibitor and 20 - lyase inhibitor is co - administered with an additional the additional therapeutic agent can be administered sequen anti - cancer agent such as mitoxantrone , paclitaxel or doc tially or simultaneously . If administered sequentially , the etaxel. For example , a method for the treatment of a cancer order of administration is flexible . For instance , 17a -hy in a mammal comprises administering an amount of abi droxylase / C17 . 20 - lyase inhibitor acetate can be administered raterone acetate and an amount of mitoxantrone . For prior to administration of the additional therapeutic agent. example , the abiraterone acetate can be administered in an Alternatively , administration of the additional therapeutic amount of about 0 .01 mg/ kg /day to about 100 mg/ kg / day agent can precede administration of 17a - hydroxylase / C , 2 . and the mitoxantrone can be administered in an amount of 20 - lyase inhibitor. about 0 . 1 mg/ m² to about 20 mg/m² . Preferably , the mitox [ 0063] Whether they are administered as separate compo antrone is administered over a period of between about 10 to sitions or in one composition , each composition is prefer about 20 minutes once every 21 days. US 2018 / 0000840 A1 Jan . 4 , 2018

[0068 ] Also , a method for the treatment of a cancer in a [0075 ] In yet another embodiment, the method for the mammal can comprise administering an amount of abirater treatment of a cancer in a mammal comprises administering one acetate and an amount of paclitaxel. In one embodiment , an amount of abiraterone acetate and an amount of fluta the abiraterone acetate can be administered in an amount of mide . For example, the method comprises administering an about 0 .01 mg/ kg / day to about 100 mg/ kg / day and the amount of about 0 .01 mg/kg /day to about 100 mg/kg /day of paclitaxel can be administered in the amount of about 1 abiraterone acetate and an amount of about 1 mg/ day to mg/ m² to about 175 mg/m² . Preferably , the paclitaxel is about 2000 mg/ day of flutamide . administered over a period of between about 2 to about 5 [0076 ) Moreover , themethod for the treatment of a cancer hours once every three months . in a mammal can comprise administering an amount of a [0069 ] Additionally, a method for the treatment of a cancer 17a -hydroxylase / C17 . 20 -lyase inhibitor such as abiraterone in a mammal comprises administering an amount of abi acetate and an amount of a glucocorticoid including, but not raterone acetate and an amount of docetaxel . For example , limited to , hydrocortisone , prednisone or dexamethasone . the abiraterone acetate can be administered in an amount of For example , the method can comprise administering an about 0 .01 mg/ kg /day to about 100 mg/ kg / day and the amount of about 50 mg/ day to about 2000 mg/ day of docetaxel can be administered in an amount of about 1 abiraterone acetate and an amount of about 0 .01 mg /day to mg/ m² to about 100 mg /m2 . Preferably , the docetaxel is about 500 mg/ day of hydrocortisone . In other instances , the administered over a period of between about 1 to about 2 method can comprise administering an amount of about 500 hours once every three weeks. mg/ day to about 1500 mg/ day of abiraterone acetate and an 0070 ] In certain embodiments , the 17a -hydroxylase /C17 . amount of about 10 mg/ day to about 250 mg/ day of hydro 20- lyase inhibitor is administered along with an anti -cancer cortisone agent that comprises a hormonal ablation agent , including , 10077 ] The method for the treatment of a cancer can also but not limited to , leuprolide, goserelin , or triptorelin . For comprise administering an amount of a 17a -hydroxylasel example , one method for the treatment of a cancer in a C17 , 20 -lyase inhibitor, such as abiraterone acetate , and an mammal also comprises administering an amount of abi amount of a glucocorticoid , such as prednisone . For raterone acetate and an amount of leuprolide. The amount of example , the method can comprise administering an amount abiraterone acetate can be about 0 .01 mg/ kg /day to about of about 50 mg/ day to about 2000 mg/ day of abiraterone 100 mg/ kg / day and the amount of leuprolide can be about acetate and an amount of about 0 .01 mg/ day to about 500 0 .01 mg to about 200 mg over a period of about 3 days to mg/ day of prednisone . Also , the method can comprise about 12 months . Preferably , the leuprolide is administered administering an amount of about 500 mg/ day to about 1500 in the amount of about 3 . 6 mg of leuprolide over a period of mg/ day of abiraterone acetate and an amount of about 10 about 3 days to about 12 months . mg/ day to about 250 mg /day of prednisone . [0071 ] Additionally, the methods for the treatment of [0078 ]. In addition , the method for the treatment of a cancer in a mammal include administering an amount of cancer can also comprise administering an amount of a abiraterone acetate and an amount of goserelin . For 17a -hydroxylase /C17 . 20 -lyase inhibitor, such as abiraterone example , the amount of abiraterone acetate can be about acetate , and an amount of a glucocorticoid , such as dexam 0 .01 mg/ kg / day to about 100 mg /kg /day and the amount of ethasone . For example , the method can comprise adminis goserelin can be about 0 . 01 mg to about 20 mg over a period tering an amount of about 50 mg/ day to about 2000 mg /day of about 28 days to about 3 months. Preferably , the goserelin of abiraterone acetate and an amount of about 0 .01 mg/ day is administered in the amount of about 3 . 6 mg to about 10 . 8 to about 500 mg/ day of dexamethasone . Also , the method mg over a period of about 28 days to about 3 months . can comprise administering an amount of about 500 mg/ day [0072 ] In certain embodiments the methods for the treat to about 1500 mg/ day of abiraterone acetate and an amount ment of cancer in a mammal comprises administering an of about 0 . 5 mg/ day to about 25 mg/ day of dexamethasone . amount of abiraterone acetate and an amount of triptorelin . Compositions Containing a 17a -hydroxylase /C17 , 20 - Lyase For example, the amount of abiraterone acetate can be about Inhibitor and an Additional Therapeutic Agent 0 .01 mg/ kg / day to about 100 mg/kg / day and the amount of [ 0079 ] In certain embodiments , the compositions can con triptorelin can be about 0 .01 mg to about 20 mg, over a tain a combination of a 17a -hydroxylase /C17 , 20 - lyase period of about 1 month , preferably the triptorelin is admin inhibitor, preferably abiraterone acetate , and any of the istered in the amount of about 3 . 75 mg over a period of about therapeutic agents recited above . Whether the 17a - hydroxy 1 month . lase /C17 . 20 - lyase inhibitor and the additional therapeutic [0073 ] Also , in one embodiment, the method for the agent are administered in separate compositions or as a treatment of a cancer in a mammal comprises administering single composition , the compositions can take various an amount of abiraterone acetate and an amount of seocal forms. For example , the compositions can take the form of citol. For instance , the method involves administering an solutions , suspensions , emulsions, tablets , pills , capsules , amount of about 0 .01 mg/ kg / day to about 100 mg/ kg /day of powders or sustained -release formulations, depending on the abiraterone acetate and an amount of about 0 . 1 ug /day to intended route of administration . about 500 ug / day of seocalcitol, such as about 100 ug / day of 0080 ) For topical or transdermal administration , the com seocalcitol. positions can be formulated as solutions, gels , ointments , [ 0074 ] In another embodiment, the method for the treat creams, suspensions or salves . ment of a cancer in a mammal comprises administering an [0081 ] For oral administration , the compositions may be amount of abiraterone acetate and an amount of bicaluta formulated as tablets , pills , dragees, troches, capsules, liq mide . For instance , the method involves administering an uids , gels , syrups, slurries , suspensions and the like, for oral amount of about 0 .01 mg /kg /day to about 100 mg/ kg /day of ingestion by a patient to be treated . abiraterone acetate and an amount of about 1 mg/ day to [ 0082] The composition may also be formulated in rectal about 300 mg / day of bicalutamide . or vaginal compositions such as suppositories or retention US 2018 / 0000840 A1 Jan . 4 , 2018

enemas that contain conventional suppository bases such as and fungi. The carrier can be a solvent or dispersion medium cocoa butter or other glycerides. containing , for example , water , ethanol, polyol ( for example, [ 0083] In addition to the formulations described previ glycerol, propylene glycol, and liquid polyethylene glycol, ously , the composition may also be formulated as a depot and the like ) , and suitable mixtures thereof. The proper preparation . Such long acting formulations may be admin fluidity can be maintained , for example , by the use of a istered by implantation ( for example subcutaneously or coating such as lecithin , by the maintenance of the required intramuscularly ) or by intramuscular injection . Thus, for particle size in the case of dispersion and by the use of example , the therapeutic agents may be formulated with surfactants . Prevention of the action ofmicroorganisms can suitable polymeric or hydrophobic materials (for example as be achieved by various antibacterial and antifungal agents , an emulsion in an acceptable oil) or ion exchange resins, or for example , parabens , chlorobutanol, phenol, ascorbic acid , as sparingly soluble derivatives, for example , as a sparingly thimerosal, and the like . In many cases , it will be preferable soluble salt . to include isotonic agents , for example , sugars; polyalcohols [ 0084 ] Additionally , the composition may be delivered such as mannitol, sorbitol; sodium chloride in the compo using a sustained -release system , such as semi- permeable sition . Prolonged absorption of the injectable compositions matrices of solid polymers containing the composition . can be brought about by including in the composition an Various forms of sustained - release materials have been agent which delays absorption , for example, aluminum established and are well known by those skilled in the art . monostearate and gelatin . Sustained -release capsules may, depending on their chemi [ 0089 ] Also for intravenous administration , the composi cal nature can release the composition over a period of tions may be formulated in solutions , preferably in physi hours , days , weeks ,months . For example a sustained release ologically compatible buffers such as Hanks 's solution , capsule can release the compositions over a period of 100 Ringer ' s solution , or physiological saline buffer . The solu days or longer. Depending on the chemical nature and the tion may contain formulatory agents such as suspending , biological stability of the composition , additional strategies stabilizing and / or dispersing agents . In a preferred embodi for stabilization may be employed . ment, the compositions are formulated in sterile solutions . [0085 ] The compositions can further comprise a pharma [ 0090 ] For transmucosal administration , penetrants appro ceutically acceptable carrier . The term " carrier ” refers to a priate to the barrier to be permeated are used in the formu diluent, adjuvant ( e . g . , Freund ' s adjuvant ( complete and lation . Such penetrants are generally known in the art , and incomplete ) ) , excipient, or vehicle with which the therapeu include , for example , for transmucosal administration , deter tic is administered . gents , bile salts , and fusidic acid derivatives . Transmucosal [ 0086 ] For parenteral administrations, the composition administration can be accomplished through the use of nasal can comprise one or more of the following carriers : a sterile sprays or suppositories. diluent such as water for injection , saline solution , fixed oils , 10091 ] For administration by inhalation , the compositions polyethylene glycols , glycerin , propylene glycol or other may be formulated as an aerosol spray from pressurized synthetic solvents ; antibacterial agents such as benzyl alco packs or a nebulizer , with the use of a suitable propellant , hol or methyl parabens ; antioxidants such as ascorbic acid or e . g . , dichlorodifluoromethane , trichlorofluoromethane , sodium hi sulfite ; chelating agents such as ethylenedi dichlorotetrafluoroethane, carbon dioxide or other suitable aminetetraacetic acid ; buffers such as acetates, citrates or gas . In the case of a pressurized aerosol, the dosage unit may phosphates and agents for the adjustment of tonicity such as be determined by providing a valve to deliver a metered sodium chloride or dextrose . The parenteral preparation can amount. Capsules and cartridges of gelatin for use in an be enclosed in ampules, disposable syringes or multiple dose inhaler or insufflator may be formulated containing a powder vials made of glass or plastic . mix of the composition and a suitable powder base such as [0087 ] For oral solid formulations suitable carriers include lactose or starch . fillers such as sugars , e . g . , lactose , sucrose , mannitol and [ 0092 ] The pharmaceutical compositions may be manu sorbitol ; cellulose preparations such as maize starch , wheat factured by means of conventional mixing , dissolving , starch , rice starch , potato starch , gelatin , gum tragacanth , granulating , dragee -making , levigating , emulsifying , encap methyl cellulose , hydroxypropylmethyl- cellulose, sodium sulating, entrapping or lyophilizing processes . carboxymethylcellulose , fats and oils ; granulating agents ; [0093 ] One example of a composition comprising a 17a and binding agents such as microcrystalline cellulose , gum hydroxylase /C17 . 20 - lyase inhibitor and an additional thera tragacanth or gelatin ; disintegrating agents , such as cross peutic agent is an oral composition or composition suitable linked polyvinylpyrrolidone , agar, or alginic acid or a salt for oral administration comprising abiraterone acetate in thereof such as sodium alginate , Primogel , or corn starch ; combination with a steroid . For example , the oral compo lubricants , such as magnesium stearate or Sterotes ; glidants , sition can be a solid dosage form such as a pill, a tablet or such as colloidal silicon dioxide ; a sweetening agent, such as a capsule . The oral composition can comprise about 10 mg , sucrose or saccharin ; or flavoring agents , such as peppetin 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, int, methyl salicylate , or orange flavoring . If desired , solid 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, dosage forms may be sugar -coated or enteric -coated using 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg , 950 mg , standard techniques. or 1000 mg of abiraterone acetate . The oral composition can [ 0088 ] For intravenous administration , suitable carriers comprises about 0 . 25 mg, 0 . 5 mg, 0 . 75 mg, 1 . 0 mg, 1 . 25 mg, include physiological saline, bacteriostatic water , phosphate 1 . 5 mg, 1 . 75 mg, 2 . 0 mg, 2 .25 mg, 2 . 5 mg, 2 .75 mg, 3 . 0 mg, buffered saline (PBS ) . In all cases, the composition must be 3 .25 mg, 3 . 5 mg, 3 .75 mg, 4 . 0 mg, 4 .25 mg, 4 . 5 mg, 4 .75 sterile and should be fluid to the extent that easy injectability mg, 5 .0 mg, 7 .5 mg, 10 mg, 20 mg , 30 mg, 40 mg or 50 mg with a syringe. It must be stable under the conditions of of a steroid , such as a glucocorticoid . manufacture and storage and must be preserved against the 0094 ] In one embodiment, the oral composition can com contaminating action of microorganisms such as bacteria prise about 50 mg to about 500 mg of abiraterone acetate and US 2018 / 0000840 A1 Jan . 4 , 2018 an amount of about 0 . 25 mg to about 3 . 5 mg of the steroid , 38 . The method of claim 37 , wherein the therapeutically such as hydrocortisone , prednisone or dexamethasone . In effective amount of the abiraterone acetate or pharmaceuti other instances , the composition can comprise about 50 mg cally acceptable salt thereof is from about 500 mg /day to to about 300 mg of abiraterone acetate and an amount of about 1500 mg/ day . about 1 . 0 mg to about 2 . 5 mg of the steroid , such as 39 . The method of claim 38 , wherein the therapeutically hydrocortisone , prednisone or dexamethasone . In another effective amount of the prednisolone is from about 0 . 25 mg/ day to about 50 mg/ day . embodiment the composition can comprise about 50 mg to 40 . The method of claim 38 , wherein the therapeutically about 300 mg of abiraterone acetate and about 0 . 5 mg to effective amount of the prednisolone is from about 5 mg/ day about 3 . 0 mg of a steroid . For example , the oral composition to about 10 mg/ day . can be a tablet containing 250 mg of abiraterone acetate ; 41. The method of claim 40 , wherein the therapeutically 1 .25 mg or 2 . 0 mg of a steroid , such as hydrocortisone , effective amount of prednisolone is about 10 mg / day . prednisone or dexamethasone ; and one or more carriers , 42 . The method of claim 37 , wherein the prednisolone is excipients , diluents or additional ingredients. Additionally , selected from prednisolone acetate , prednisolone sodium the oral composition can be a capsule containing 250 mg of phosphate , and prednisolone tebutate . abiraterone acetate ; 1 .25 mg or 2 . 0 mg of a steroid , such as 43 . A method for the treatment of a refractory prostate hydrocortisone , prednisone or dexamethasone ; and one or cancer in a human comprising administering to said human more carriers , excipients , diluents or additional ingredients . a therapeutically effective amount of abiraterone acetate or [0095 ] The description contained herein is for purposes of a pharmaceutically acceptable salt thereof and a therapeu illustration and not for purposes of limitation . The methods tically effective amount of a prednisolone . and compositions described herein can comprise any feature 44 . The method of claim 43, wherein the therapeutically effective amount of the abiraterone acetate or pharmaceuti described herein either alone or in combination with any cally acceptable salt thereof is from about 500 mg/ day to other feature (s ) described herein . Changes and modifications about 1500 mg/ day . may be made to the embodiments of the description . Fur 45 . The method of claim 44 , wherein the therapeutically thermore , obvious changes , modifications or variations will effective amount of the prednisolone is from about 0 . 25 occur to those skilled in the art. Also , all references cited mg/ day to about 50 mg/ day . above are incorporated herein , in their entirety , for all 46 . The method of claim 44 , wherein the therapeutically purposes related to this disclosure . effective amount of the prednisolone is from about 5 mg/ day to about 10 mg/ day . 1- 36 . (canceled ) 47 . The method of claim 46 , wherein the therapeutically 37. A method for the treatment of a prostate cancer in a effective amount of prednisolone is about 10 mg/ day . human comprising administering to said human a therapeu 48 . The method of claim 43 , wherein the prednisolone is tically effective amount of abiraterone acetate or a pharma selected from prednisolone acetate , prednisolone sodium ceutically acceptable salt thereof and a therapeutically effec phosphate , and prednisolone tebutate . tive amount of a prednisolone . * * * * *