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A Phase I, dose-finding and pharmacokinetic study of olaparib (AZD2281) in Japanese patients with advanced solid

Noboru Yamamoto1, Hiroshi Nokihara, Yasuhide Yamada

  • 1National Cancer Center Hospital, Tokyo, Japan. nbryamam@ncc.go.jp

Cancer Science
|December 8, 2011
PubMed

Insights

Olaparib, a PARP inhibitor, was well tolerated in Japanese patients with solid tumors up to 400 mg twice daily. Preliminary antitumor activity was observed, supporting further investigation in this population.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • Olaparib (AZD2281) is an oral Poly(ADP-ribose) polymerase (PARP) inhibitor.
  • Previous studies showed antitumor activity in ovarian and breast cancers with BRCA1/2 mutations.

Purpose of the Study:

  • Evaluate olaparib's tolerability, pharmacokinetics, PARP inhibition, and antitumor activity.
  • Assess olaparib in Japanese patients with solid tumors.

Main Methods:

  • Phase I dose-finding study.
  • Oral olaparib administered single-dose then twice-daily for 28 days.
  • Dose escalation from 100 mg to 400 mg twice daily in 12 patients.

Main Results:

  • Olaparib was well tolerated up to 400 mg twice daily; no dose-limiting toxicities observed.
  • PARP-1 inhibition confirmed in peripheral blood mononuclear cells.
  • One partial response (metastatic breast cancer) and four cases of stable disease (>8 weeks) observed.

Conclusions:

  • Olaparib is well tolerated and shows preliminary antitumor activity in Japanese patients with solid tumors.
  • Pharmacokinetics and PARP inhibition were consistent with Western studies.
  • Further investigation of olaparib in this patient population is warranted.

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