title: A phase I multicenter study of antroquinonol in patients with metastatic non-small-cell lung cancer who have received at least two prior systemic treatment regimens, including one platinum-based chemotherapy regimen.
abstract: Antroquinonol is isolated fromAntrodia camphorata, a camphor tree mushroom, and is a valuable traditional Chinese herbal medicine that exhibits pharmacological activities against several diseases, including cancer. This first-in-human phase I study of antroquinonol included patients with metastatic non-small-cell lung cancer who had received at least two prior systemic treatment regimens. An open-label, dose escalation, pharmacokinetic (PK) study was conducted to determine the maximum tolerable dose (MTD), dose-limiting toxicities (DLTs), and safety/tolerability and preliminary efficacy profiles of antroquinonol. The patients received escalating doses of once-daily antroquinonol in 4-week cycles (up to 3 cycles). The escalated doses were 50-600 mg. PKs were evaluated on day 1 and 28 of cycle 1. Between January, 2011 and October, 2012, 13 patients with metastatic adenocarcinoma were enrolled. No DLTs occurred in any patient at any dose level. Tmaxwas observed between 1.00 and 3.70 h under single-dose conditions, and at 1.92-4.05 h under multiple-dose conditions. The mean elimination half-life ranged between 1.30 and 4.33 h, independent of the treatment dose. Antroquinonol at all dose levels had a mild toxicity profile, with no reported treatment-related mortality. The most common treatment-related adverse events were diarrhea, vomiting and nausea. The best tumor response was stable disease in 3 patients. In conclusion, antroquinonol at all dose levels, administered daily for 4 weeks, was generally safe and well tolerated, without DLTs. The recommended dose level for a phase II study is ≥600 mg daily.
authors.affiliation: Sijhih Cathay General Hospital, New Taipei 221, Taiwan, R.O.C.; School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, R.O.C.
authors.forename: Yu-Chin
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.
authors.forename: Ching-Liang
authors.initials: CL
authors.lastname: Ho
authors.affiliation: Taipei Tzu Chi General Hospital, Taipei 231, Taiwan, R.O.C.
authors.forename: Woei-Yau
authors.initials: WY
authors.lastname: Kao
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, R.O.C.; Department of Chest Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C.; College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan, R.O.C.
authors.forename: Yuh-Min
authors.initials: YM
authors.lastname: Chen
keywords: Antrodia camphorata; antroquinonol; lung cancer; phase I