PMID- 30887180
OWN - NLM
STAT- MEDLINE
DCOM- 20200212
LR  - 20200212
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 83
IP  - 5
DP  - 2019 May
TI  - 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.
PG  - 963-974
LID - 10.1007/s00280-019-03799-1 [doi]
AB  - 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/m(2)) 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.
FAU - Yuan, Peng
AU  - Yuan P
AD  - National Clinical Research Center for Cancer/Cancer Hospital, National Cancer 
      Center, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical 
      College (PUMC), No. 17 Panjiayuan, Chaoyang District, Beijing, 100021, China.
FAU - Shentu, Jianzhong
AU  - Shentu J
AD  - Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and 
      Treatment of Infectious Disease, The First Affiliated Hospital of Zhejiang 
      University, Zhejiang, China.
FAU - Xu, Jianming
AU  - Xu J
AD  - Affiliated Hospital Cancer Center, The 307th Hospital of Chinese People's 
      Liberation Army, Academy of Military Medical Sciences, Beijing, China.
FAU - Burke, Wendy
AU  - Burke W
AD  - Covance Clinical Research Unit, Leeds, UK.
FAU - Hsu, Kate
AU  - Hsu K
AD  - AstraZeneca, Shanghai, China.
FAU - Learoyd, Maria
AU  - Learoyd M
AD  - AstraZeneca, Cambridge, UK.
FAU - Zhu, Min
AU  - Zhu M
AD  - AstraZeneca, Shanghai, China.
FAU - Xu, Binghe
AU  - Xu B
AD  - National Clinical Research Center for Cancer/Cancer Hospital, National Cancer 
      Center, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical 
      College (PUMC), No. 17 Panjiayuan, Chaoyang District, Beijing, 100021, China. 
      xubinghe@medmail.com.cn.
LA  - eng
SI  - ClinicalTrials.gov/NCT02430311
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190318
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Phthalazines)
RN  - 0 (Piperazines)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 0 (Tablets)
RN  - P88XT4IS4D (Paclitaxel)
RN  - WOH1JD9AR8 (olaparib)
SB  - IM
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - China
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Paclitaxel/administration & dosage
MH  - Phthalazines/*administration & dosage/adverse effects/pharmacokinetics
MH  - Piperazines/*administration & dosage/adverse effects/pharmacokinetics
MH  - Poly(ADP-ribose) Polymerase Inhibitors/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Tablets
OTO - NOTNLM
OT  - Chinese patients
OT  - Olaparib
OT  - PARP inhibitor
OT  - Paclitaxel
OT  - Pharmacokinetics
OT  - Safety
EDAT- 2019/03/20 06:00
MHDA- 2020/02/13 06:00
CRDT- 2019/03/20 06:00
PHST- 2018/10/17 00:00 [received]
PHST- 2019/02/11 00:00 [accepted]
PHST- 2019/03/20 06:00 [pubmed]
PHST- 2020/02/13 06:00 [medline]
PHST- 2019/03/20 06:00 [entrez]
AID - 10.1007/s00280-019-03799-1 [pii]
AID - 10.1007/s00280-019-03799-1 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2019 May;83(5):963-974. doi: 
      10.1007/s00280-019-03799-1. Epub 2019 Mar 18.