التفاصيل البيبلوغرافية
| العنوان: |
A Phase I Study of Capivasertib in Combination With Abiraterone Acetate in Patients With Metastatic Castration-Resistant Prostate Cancer. |
| المؤلفون: |
Shore, Neal1, Mellado, Begoña2, Shah, Satish3, Hauke, Ralph4, Costin, Dan5, Adra, Nabil6, Cullberg, Marie7, Teruel, Carlos Fernandez8, Morris, Thomas9 |
| المصدر: |
Clinical Genitourinary Cancer. Apr2023, Vol. 21 Issue 2, p278-285. 8p. |
| مصطلحات موضوعية: |
*ANTINEOPLASTIC agents, *ABIRATERONE acetate, *CASTRATION-resistant prostate cancer, *METASTASIS, *PHARMACOKINETICS |
| مستخلص: |
Patients with metastatic prostate cancer can develop PI3K/AKT/PTEN pathway-associated resistance to androgen receptor-targeted therapy. In an open-label phase Ib study, 27 systemically treated patients received abiraterone acetate plus capivasertib, a potent, selective pan-AKT inhibitor. The combination demonstrated acceptable tolerability with no dose-limiting toxicity and pharmacokinetics consistent with monotherapy dosing. These data support further clinical evaluation in this patient population. Background: Although androgen receptor-targeted agents prolong the lives of patients with metastatic prostate cancer, patients develop therapy resistance and most ultimately succumb to the disease. The PI3K/AKT/PTEN pathway has been associated with the development of resistance, raising the possibility that pathway inhibitors may produce a clinical benefit. This open-label phase Ib study examined the safet y, tolerabilit y, pharmacokinetics (PK) and preliminary clinical activity of adding capivasertib - a potent, selective inhibitor of AKT1/2/3 - to approved abiraterone acetate therapy. Methods: Twenty-seven patients with metastatic castration-resistant prostate cancer who had undergone at least 1 prior line of systemic therapy received abiraterone acetate 1000 mg (orally administered once daily), plus oral prednisone 5 mg (twice daily) with capivasertib 400 mg (orally, twice daily, with an intermittent schedule of 4 days on, 3 days off). Results: No dose-limiting toxicity was observed. The most frequent adverse events (all grade) were diarrhea (30%), anemia (26%), asthenia (22%), and nausea (22%). The most frequent grade 3 or higher adverse events were acute kidney injury (19%), hyperglycemia (7%), rash (7%), abdominal pain (7%), and asthenia (7%). Capivasertib and abiraterone PK were consistent with previously reported results from monotherapy dosing. Nine participants (33%) showed a 20% or greater decrease in prostate-specific antigen during study treatment. Conclusion: The combination of capivasertib and abiraterone acetate had an acceptable tolerability profile consistent with the known profile of each agent. These data support further evaluation of capivasertib and abiraterone acetate in patients with advanced prostate cancer. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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