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Cancer Chemotherapy and Pharmacology

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18.03.2019 | Original Article

Pharmacokinetics and safety of olaparib tablets as monotherapy and in combination with paclitaxel: results of a Phase I study in Chinese patients with advanced solid tumours

verfasst von: Peng Yuan, Jianzhong Shentu, Jianming Xu, Wendy Burke, Kate Hsu, Maria Learoyd, Min Zhu, Binghe Xu

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2019

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Abstract

Purpose

Chinese patients have been enrolled in multiple Phase III trials of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza); however, the pharmacokinetic (PK) profile of olaparib has not been investigated in this population. This two-part, open-label Phase I study was, therefore, carried out to determine the PK and safety profile of olaparib (tablet formulation) in Chinese patients with advanced solid tumours as monotherapy and in combination with paclitaxel (NCT02430311).

Methods

The PK profile of olaparib 300 mg (twice daily [bid]; Cohort 1) as monotherapy after a single dose and at steady state, and 100 mg (bid; Cohort 2) as monotherapy (single dose and at steady state) and in combination (at steady state) with weekly paclitaxel (80 mg/m²) was assessed during Part A. Patients could continue to receive treatment (monotherapy, Cohort 1; combination therapy, Cohort 2) in Part B, which assessed safety and tolerability.

Results

Twenty and 16 patients were enrolled into Cohorts 1 and 2, respectively. Steady-state olaparib exposure increased slightly less than proportionally with increasing monotherapy dose and inter-patient variability was high. A statistically significant decrease in olaparib exposure was seen when given in combination with paclitaxel. Discontinuation due to adverse events (AEs) was rare and haematological AEs were more common in patients receiving combination treatment.

Conclusions

The PK and safety profile of olaparib monotherapy in Chinese patients is consistent with that seen previously in Western and Japanese patients, and the recommended Phase III monotherapy tablet dose (300 mg bid) is suitable for use in this population.

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Titel: Pharmacokinetics and safety of olaparib tablets as monotherapy and in combination with paclitaxel: results of a Phase I study in Chinese patients with advanced solid tumours
verfasst von: Peng Yuan
Jianzhong Shentu
Jianming Xu
Wendy Burke
Kate Hsu
Maria Learoyd
Min Zhu
Binghe Xu
Publikationsdatum: 18.03.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2019
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-03799-1

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Pharmacokinetics and safety of olaparib tablets as monotherapy and in combination with paclitaxel: results of a Phase I study in Chinese patients with advanced solid tumours

Abstract

Purpose

Methods

Results

Conclusions

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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