Abstract | LESSONS LEARNED: Pharmacokinetic results underscore that the vorolanib (X-82) study design was successful without the need for further dose escalation beyond 400 mg once daily (q.d.).Therefore, the recommended dose of X-82 as a single agent in patients with advanced cancer is 400 mg q.d. BACKGROUND: METHODS: Adult patients with advanced solid tumors received X-82 as tablets or capsules (once daily [q.d.] or b.i.d.) every 4 weeks. Patients were evaluated for response every 8 weeks, and continued treatment until disease progression or intolerable toxicity. RESULTS: Fifty-two patients received study treatment in 17 cohorts. X-82 capsule dosing was as follows: cohorts 1-6 (20-400 mg q.d.) and cohorts 7-8 (140-200 mg b.i.d.). Patients in cohorts 9-17 received 50-800 mg q.d. tablet dosing. The median time on treatment was 58 days. X-82 blood pharmacokinetics appeared dose-independent with a t 1/2 of 5.13 hours and 6.48 hours for capsule and tablet formulations, respectively. No apparent accumulation was observed after 21 days of daily dosing. CONCLUSION: X-82 had a safety profile consistent with its mechanism of action. It has a short half-life and was well tolerated by most patients. Study enrollment ended prior to the determination of the MTD because of the apparent saturation of absorption at 400-800 mg. The recommended dose of X-82 as a single agent in patients with advanced cancer is 400 mg q.d.
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Authors | Johanna C Bendell, Manish R Patel, Kathleen N Moore, Cynthia C Chua, Hendrik-Tobias Arkenau, Gary Dukart, Kim Harrow, Chris Liang |
Journal | The oncologist
(Oncologist)
Vol. 24
Issue 4
Pg. 455-e121
(04 2019)
ISSN: 1549-490X [Electronic] England |
PMID | 30478190
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © AlphaMed Press; the data published online to support this summary are the property of the authors. |
Chemical References |
- Indoles
- Protein Kinase Inhibitors
- Pyrroles
- Pyrrolidines
- vorolanib
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Drug Administration Schedule
- Female
- Follow-Up Studies
- Humans
- Indoles
(pharmacokinetics, therapeutic use)
- Male
- Maximum Tolerated Dose
- Middle Aged
- Neoplasms
(drug therapy)
- Patient Safety
- Prognosis
- Protein Kinase Inhibitors
(pharmacokinetics, therapeutic use)
- Pyrroles
(pharmacokinetics, therapeutic use)
- Pyrrolidines
(pharmacokinetics, therapeutic use)
- Survival Rate
- Tissue Distribution
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