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Phase I study of OPB-51602, an oral inhibitor of signal transducer and activator of transcription 3, in patients with relapsed/refractory hematological malignancies.

Ogura M, Uchida T, Terui Y, Hayakawa F, Kobayashi Y, Taniwaki M, Takamatsu Y, Naoe T, Tobinai K, Munakata W, Yamauchi T, Kageyama A, Yuasa M, Motoyama M, Tsunoda T, Hatake K - Cancer Sci. (2015)

Bottom Line: In conclusion, the MTD of OPB-51602 was 6 mg.OPB-51602 was safe and well tolerated in a dose range of 1-4 mg.However, long-term administration at higher doses was difficult with the daily dosing schedule, and no response was seen.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Japan.

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Related in: MedlinePlus

Time-course of the mean plasma con-centration of OPB-51602 after single administration (a) and multiple administrations on day 28 (b). Plasma concentrations below the lower limit of quantification were considered to be 0 ng/mL. Values are the mean ± SD.
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fig01: Time-course of the mean plasma con-centration of OPB-51602 after single administration (a) and multiple administrations on day 28 (b). Plasma concentrations below the lower limit of quantification were considered to be 0 ng/mL. Values are the mean ± SD.

Mentions: OPB-51602 was rapidly absorbed after both single and multiple administrations. The median time to reach the maximum plasma concentration (tmax) was between 2.0 and 4.5 h (Table3, Fig.1). For the lower dose groups (the 1- and 2-mg cohorts), terminal-phase elimination half-life (t1/2,z) was evaluable in a few patients due to low OPB-51602 plasma levels after single administration. The mean t1/2,z was 50.1–240.0 h after multiple administrations. Exposure (area under the plasma concentration–time curve from 0 to 24 h [AUC24 h] and maximum plasma drug concentration [Cmax]) tended to increase in a dose-dependent manner following multiple administrations across the dose range from 1 to 4 mg (Table3). We observed accumulation of OPB-51602 with a 2.6–10.2-fold increase in AUC24 h and a 1.4–4.6-fold increase in Cmax with doses of 1, 2, 3, and 4 mg.


Phase I study of OPB-51602, an oral inhibitor of signal transducer and activator of transcription 3, in patients with relapsed/refractory hematological malignancies.

Ogura M, Uchida T, Terui Y, Hayakawa F, Kobayashi Y, Taniwaki M, Takamatsu Y, Naoe T, Tobinai K, Munakata W, Yamauchi T, Kageyama A, Yuasa M, Motoyama M, Tsunoda T, Hatake K - Cancer Sci. (2015)

Time-course of the mean plasma con-centration of OPB-51602 after single administration (a) and multiple administrations on day 28 (b). Plasma concentrations below the lower limit of quantification were considered to be 0 ng/mL. Values are the mean ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4520642&req=5

fig01: Time-course of the mean plasma con-centration of OPB-51602 after single administration (a) and multiple administrations on day 28 (b). Plasma concentrations below the lower limit of quantification were considered to be 0 ng/mL. Values are the mean ± SD.
Mentions: OPB-51602 was rapidly absorbed after both single and multiple administrations. The median time to reach the maximum plasma concentration (tmax) was between 2.0 and 4.5 h (Table3, Fig.1). For the lower dose groups (the 1- and 2-mg cohorts), terminal-phase elimination half-life (t1/2,z) was evaluable in a few patients due to low OPB-51602 plasma levels after single administration. The mean t1/2,z was 50.1–240.0 h after multiple administrations. Exposure (area under the plasma concentration–time curve from 0 to 24 h [AUC24 h] and maximum plasma drug concentration [Cmax]) tended to increase in a dose-dependent manner following multiple administrations across the dose range from 1 to 4 mg (Table3). We observed accumulation of OPB-51602 with a 2.6–10.2-fold increase in AUC24 h and a 1.4–4.6-fold increase in Cmax with doses of 1, 2, 3, and 4 mg.

Bottom Line: In conclusion, the MTD of OPB-51602 was 6 mg.OPB-51602 was safe and well tolerated in a dose range of 1-4 mg.However, long-term administration at higher doses was difficult with the daily dosing schedule, and no response was seen.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Japan.

Show MeSH
Related in: MedlinePlus