ライフサイエンスコーパス: abiraterone

1 nd treatment type (taxane vs enzalutamide or abiraterone).

2 sociated with resistance to enzalutamide and abiraterone.

3 iating treatment with either enzalutamide or abiraterone.

4 the clinical efficacy of the CYP17 inhibitor abiraterone.

5 , bicalutamide, or greater concentrations of abiraterone.

6 aracterized with different concentrations of abiraterone.

7 mour activity against xenograft tumours than abiraterone.

8 sociated with resistance to enzalutamide and abiraterone.

9 were randomly assigned (1:1) to receive oral abiraterone (1 g daily) plus prednisone (5 mg twice dail

10 ly as abiraterone acetate (AA), a prodrug of abiraterone, a CYP17 inhibitor that lowers serum testost

11 hich were obtained in the presence of either abiraterone, a first-in-class steroidal inhibitor recent

12 Abiraterone, a rationally designed inhibitor of CYP17A1

13 Unexplored electrochemical behavior of abiraterone, a recent and widely used prostate cancer dr

14 Abiraterone acetate is a prodrug of abiraterone, a selective inhibitor of CYP17, the enzyme

15 Abiraterone, a steroidal 17alpha-hydroxylase/17,20-lyase

16 The CYP17A1 inhibitor abiraterone abolished androgen secretion and reduced exp

17 Patients received oral abiraterone acetate (1 g) once daily and prednisone (5 m

18 a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate (1000 mg daily) and prednisolone (5

19 Participants received oral doses of abiraterone acetate (1000 mg daily) and prednisone (5 mg

20 onse system in a 1:1 ratio to receive either abiraterone acetate (1000 mg once daily) plus prednisone

21 e randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5 mg twic

22 rednisone twice daily with either 1000 mg of abiraterone acetate (797 patients) or placebo (398 patie

23 Abiraterone acetate (AA) is a potent and selective inhib

24 In the phase III study COU-AA-301, abiraterone acetate (AA) plus prednisone (P) prolonged o

25 not reduce serum androgens as effectively as abiraterone acetate (AA), a prodrug of abiraterone, a CY

26 this multicenter, two-stage, phase II study, abiraterone acetate 1,000 mg was administered once daily

27 This is the first evidence that abiraterone acetate achieves sustained suppression of te

28 ls of novel hormonal agents, with a focus on abiraterone acetate and enzalutamide (MDV3100).

29 t of novel anti-androgen therapies including abiraterone acetate and enzalutamide.

30 Phase III data with abiraterone acetate and phase II data with MDV-3100, alo

31 te cancer previously treated with docetaxel, abiraterone acetate and prednisone offer significant ben

32 ith clinically significant pain at baseline, abiraterone acetate and prednisone resulted in significa

33 7]; p=0.0056) were significantly better with abiraterone acetate and prednisone than with prednisone

34 -related event was significantly longer with abiraterone acetate and prednisone than with prednisone

35 Randomized, phase III trials of abiraterone acetate are underway to define the future ro

36 n, development of sustained side-effects, or abiraterone acetate becoming available in the respective

37 Fasted or fed cohorts received abiraterone acetate doses of 250, 500, 750, or 1,000 mg

38 This phase I dose-escalation study of abiraterone acetate evaluated safety, pharmacokinetics,

39 n this early-access protocol trial to assess abiraterone acetate for patients with metastatic castrat

40 n observed: 354 (65%) of 546 patients in the abiraterone acetate group and 387 (71%) of 542 in the pl

41 Overall, 365 (67%) patients in the abiraterone acetate group and 435 (80%) in the placebo g

42 all survival was significantly longer in the abiraterone acetate group than in the placebo group (34.

43 ac disorders (41 [8%] of 542 patients in the abiraterone acetate group vs 20 [4%] of 540 patients in

44 ce daily) plus prednisone (5 mg twice daily; abiraterone acetate group) or placebo plus prednisone (p

45 Abiraterone acetate has significant antitumor activity i

46 her support the favourable safety profile of abiraterone acetate in patients with chemotherapy-naive

47 01 to enable worldwide preapproval access to abiraterone acetate in patients with metastatic castrati

48 Abiraterone acetate is a prodrug of abiraterone, a selec

49 or men with metastatic CRPC, and approval of abiraterone acetate is anticipated based on the results

50 Abiraterone acetate plus prednisolone improves survival

51 The abiraterone acetate plus prednisone and prednisone-alone

52 iving prednisone alone subsequently received abiraterone acetate plus prednisone as crossover per pro

53 alysis of the trial, assessing the effect of abiraterone acetate plus prednisone on overall survival,

54 Abiraterone acetate plus prednisone significantly improv

55 Abiraterone acetate plus prednisone significantly improv

56 al analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolon

57 the randomised, phase 3 COU-AA-301 trial of abiraterone acetate plus prednisone versus placebo plus

58 he individual-patient level in this trial of abiraterone acetate plus prednisone versus prednisone al

59 randomized, double-blind phase III trial of abiraterone acetate plus prednisone versus prednisone al

60 ng/mL or lower within 12 months of starting abiraterone acetate plus prednisone.

61 Abiraterone acetate potently disrupts intracrine androge

62 The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among pat

63 llow-up of more than 4 years, treatment with abiraterone acetate prolonged overall survival compared

64 d to ascertain the most effective regimen of abiraterone acetate to optimise patients' outcomes.

65 Abiraterone acetate was well tolerated and demonstrated

66 Abiraterone acetate was well tolerated.

67 To determine the efficacy of abiraterone acetate with prednisone in these high-risk p

68 Abiraterone acetate, 1000 mg, once daily by mouth with p

69 Abiraterone acetate, 1000 mg, once daily with prednisone

70 In the past year abiraterone acetate, a CYP17 (17alpha-hydroxylase/17, 20

71 with overexpressed androgen receptor, and by abiraterone acetate, a CYP17A inhibitor that blocks ster

72 Abiraterone acetate, an androgen biosynthesis inhibitor,

73 Journal of Medicine describe the utility of abiraterone acetate, an androgen biosynthesis inhibitor,

74 We evaluated whether abiraterone acetate, an inhibitor of androgen biosynthes

75 al was to evaluate the antitumor activity of abiraterone acetate, an oral, specific, irreversible inh

76 A third agent, abiraterone acetate, an orally administered CYP17 inhibi

77 el CYP17 inhibitors, including ketoconazole, abiraterone acetate, and VN/124-1, which are agents curr

78 for these patients have expanded to include abiraterone acetate, cabazitaxel and enzalutamide.

79 The development of cabazitaxel, abiraterone acetate, enzalutamide, radium-223, and sipul

80 5%) of the 40 received PRO-related labeling (abiraterone acetate, ruxolitinib phosphate, and crizotin

81 8 months, overall survival was longer in the abiraterone acetate-prednisone group than in the placebo

82 alemia, were more frequently reported in the abiraterone acetate-prednisone group than in the placebo

83 ecline in CTCs after starting treatment with abiraterone acetate.

84 l patients who received at least one dose of abiraterone acetate.

85 , and favorable benefit-harm balance include abiraterone acetate/prednisone, enzalutamide, and radium

86 Abiraterone acetate/prednisone, enzalutamide, or (223)Ra

87 reduced by TOK-001 and to a lesser extent by abiraterone alcohol, and suggest a mechanism by which ca

88 In a clinical trial of abiraterone alone, followed by abiraterone plus dutaster

89 a 5alpha-reductase inhibitor), 3-keto-5alpha-abiraterone and downstream metabolites were depleted by

90 orrelated with poor outcomes from the use of abiraterone and enzalutamide in patients with castration

91 However, resistance to abiraterone and enzalutamide limits this efficacy in mos

92 radiation (alpharadin) and hormone therapy (abiraterone and enzalutamide) agents has created a range

93 R activity in CRPC, mechanisms of action for abiraterone and enzalutamide, and possible mechanisms of

94 ese agents, the androgen-pathway inhibitors, abiraterone and enzalutamide, are shown to decrease the

95 sis and androgen-receptor signaling, such as abiraterone and enzalutamide, respectively.

96 PC) with next-generation endocrine therapies abiraterone and enzalutamide.

97 tent second-generation AR-targeted therapies abiraterone and enzalutamide.

98 al trials, secondary hormonal agents such as abiraterone and MDV3100 may still be very effective in t

99 n therapies including CRPC therapies such as abiraterone and MDV3100.

100 e cohort, while two additional cohorts (post-abiraterone and newly castration-resistant prostate canc

101 nced or metastatic prostate cancer, ADT plus abiraterone and prednisolone was associated with signifi

102 d therapies targeting AR signalling, such as abiraterone and second-generation anti-androgens includi

103 ing synthetic inhibitors, including the drug abiraterone and the natural substrate pregnenolone, in t

104 17A1 and 17A2 were obtained with the ligand abiraterone and with Prog for P450 17A2.

105 n with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned a

106 and progressive disease after docetaxel and abiraterone and/or enzalutamide.

107 l efficacy of androgen synthesis inhibitors (abiraterone) and novel, second-generation AR antagonists

108 D4A in patients with prostate cancer taking abiraterone, and is an androgen receptor agonist, which

109 to improve survival with the lyase inhibitor abiraterone, and lead to prostate-specific antigen and o

110 Similarly, among men receiving abiraterone, AR-V7-positive patients had lower PSA respo

111 CYP17A1, so that CYP17A1 inhibitors such as abiraterone are effective therapies for CRPC.

112 TOK-001 and abiraterone are potent 17-heteroarylsteroid (17-HAS) inh

113 Abiraterone blocks androgen synthesis and prolongs survi

114 ain, which is the target of enzalutamide and abiraterone, but remains constitutively active as a tran

115 ancer, with the recently developed inhibitor abiraterone currently in advanced clinical trials.

116 ted by an enzyme to the more active Delta(4)-abiraterone (D4A), which blocks multiple steroidogenic e

117 erone is metabolized in patients to Delta(4)-abiraterone (D4A), which has even greater anti-tumour ac

118 Simulations with standard abiraterone dosing demonstrate strong selection for andr

119 Abiraterone, enzalutamide, and other agents can improve

120 ger in patients who received radium-223 plus abiraterone, enzalutamide, or both (median NA, 95% CI 16

121 urvival in patients treated with concomitant abiraterone, enzalutamide, or denosumab require confirma

122 Therefore, an increase in abiraterone exposure could reverse resistance secondary

123 ens, has been exemplified by the approval of abiraterone for the treatment of castration-resistant pr

124 The introduction of enzalutamide and abiraterone has led to improvement in the treatment of m

125 Abiraterone improved radiographic progression-free survi

126 ary end point of OS in a randomized trial of abiraterone in patients with mCRPC.

127 provide further support for the efficacy of abiraterone in this population.

128 and CRPC xenografts treated with MDV3100 or abiraterone, increased expression of two constitutively

129 Abiraterone inhibited in vitro proliferation and AR-regu

130 Further, we observed that seviteronel and abiraterone inhibited the growth of tumor xenografts exp

131 urvival advantage in CRPC for treatment with abiraterone (inhibitor of the enzyme CYP17A1 required fo

132 We hypothesized that abiraterone is converted by an enzyme to the more active

133 Here we show that abiraterone is converted to D4A in mice and patients wit

134 astration-resistant prostate cancer (mCRPC), abiraterone is effective.

135 Abiraterone is metabolized in patients to Delta(4)-abira

136 Abiraterone is structurally similar to the substrates of

137 TOK-001, but not abiraterone, is an effective apparent competitor of the

138 ial 5alpha-reduced metabolite, 3-keto-5alpha-abiraterone, is present at higher concentrations than D4

139 V7-negative men, taxanes and enzalutamide or abiraterone may have comparable efficacy.

140 we hypothesized that progressive disease on abiraterone may occur secondary to glucocorticoid-induce

141 nonetheless, expectations for other agents (Abiraterone, MDV3100, Zibotentan, immunotherapy agents)

142 ly specific method of clinically fine-tuning abiraterone metabolism to optimize therapy.

143 armacological 5alpha-reductase inhibition on abiraterone metabolism.

144 01 is a consistently superior inhibitor than abiraterone of R1881-induced transcriptional activity of

145 ely enrolled 202 patients with CRPC starting abiraterone or enzalutamide and investigated the prognos

146 sis ( P = .01), higher PSA ( P < .01), prior abiraterone or enzalutamide use ( P = .03), prior taxane

147 um, number of prior hormone therapies, prior abiraterone or enzalutamide use, prior taxane use, prese

148 atment with docetaxel, 49 (98%) had received abiraterone or enzalutamide, and 29 (58%) had received c

149 that radium-223 can be safely combined with abiraterone or enzalutamide, which are now both part of

150 raphic evidence, and previous treatment with abiraterone or enzalutamide.

151 ical trial of abiraterone alone, followed by abiraterone plus dutasteride (a 5alpha-reductase inhibit

152 intensity was longer in patients assigned to abiraterone plus prednisone (26.7 months [95% CI 19.3-no

153 ogression of worst pain was also longer with abiraterone plus prednisone (26.7 months [95% CI 19.4-no

154 nderwent randomisation: 546 were assigned to abiraterone plus prednisone and 542 to placebo plus pred

155 Abiraterone plus prednisone delays patient-reported pain

156 of 1,088 patients were randomly assigned to abiraterone plus prednisone or prednisone alone.

157 stases and minimal symptoms, enzalutamide or abiraterone plus prednisone should be offered after disc

158 rioration was longer in patients assigned to abiraterone plus prednisone than in those assigned to pl

159 ified by ETS status and randomly assigned to abiraterone plus prednisone without (arm A) or with veli

160 ew was 0.43 (95% CI, 0.35 to 0.52; P < .001; abiraterone plus prednisone: median rPFS, not estimable;

161 2 months, overall survival was improved with abiraterone-prednisone (median not reached, vs. 27.2 mon

162 ogression-free survival was 16.5 months with abiraterone-prednisone and 8.3 months with prednisone al

163 Abiraterone-prednisone showed superiority over prednison

164 nths with prednisone alone (hazard ratio for abiraterone-prednisone vs. prednisone alone, 0.53; 95% c

165 liver-function testing were more common with abiraterone-prednisone.

166 or cells with resistance to enzalutamide and abiraterone raise the possibility of extending the use o

167 We demonstrate that both TOK-001 and abiraterone reduced AR protein and mRNA expression, and

168 tor, providing an additional explanation for abiraterone's clinical activity.

169 nation-conversion to a more active agent-for abiraterone's survival extension.

170 Comparison of the two fish P450 17A-abiraterone structures with human P450 17A1 showed only

171 ults with next generation drugs (MDV3100 and abiraterone) that inhibit androgen receptor (AR) signali

172 ver, acquired resistance to enzalutamide and abiraterone therapies frequently develops within a short

173 r with taxanes compared with enzalutamide or abiraterone therapy in AR-V7-positive men, whereas outco

174 with primary resistance to enzalutamide and abiraterone therapy, but the relevance of AR-V7 status i

175 to be more efficacious than enzalutamide or abiraterone therapy, whereas in AR-V7-negative men, taxa

176 higher in taxane-treated vs enzalutamide- or abiraterone-treated men (41% vs 0%; P < .001), and PSA P

177 l of 31 enzalutamide-treated patients and 31 abiraterone-treated patients were enrolled, of whom 39%

178 pendent de novo androgen synthesis, and that abiraterone treatment of these xenografts imposes select

179 promiscuous AR T878A in patients with prior abiraterone treatment.

180 D4A would be more clinically effective than abiraterone treatment.

181 Abiraterone treats metastatic castrate-resistant prostat

182 of 62 patients treated with enzalutamide or abiraterone, we also investigated the interaction betwee

183 y demonstrated the direct electroactivity of abiraterone when reacting with MWCNT as well as an elect

184 sociate with a reduced clinical benefit from abiraterone when these tumors progress.

185 FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar

186 nonetheless, expectations for other agents (abiraterone, zibotentan, Provenge) still remain high.