Ontology highlight
ABSTRACT: Background
This phase I, dose-finding study determined the safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), pharmacokinetics, and antitumour activity of PX-866, a phosphatidylinositol 3-kinase inhibitor, combined with docetaxel in patients with incurable solid tumours.Methods
PX-866 was administered at escalating doses (4-8 mg daily) with docetaxel 75 mg m?² intravenously every 21 days. Archived tumour tissue was assessed for potential predictive biomarkers.Results
Forty-three patients were enrolled. Most adverse events (AEs) were grade 1 or 2. The most frequent study drug-related AE was diarrhoea (76.7%), with gastrointestinal disorders occurring in 79.1% (docetaxel-related) and 83.7% (PX-866-related). No dose-limiting toxicities were observed. The RP2D was 8 mg, the same as the single-agent MTD. Co-administration of PX-866 and docetaxel did not affect either drug's PKs. Best responses in 35 evaluable patients were: 2 partial responses (6%), 22 stable disease (63%), and 11 disease progression (31%). Eleven patients remained on study for >180 days, including 8 who maintained disease control on single-agent PX-866. Overall median progression-free survival (PFS) was 73.5 days (range: 1-569). A non-significant association between longer PFS for PIK3CA-MUT/KRAS-WT vs PIK3CA-WT/KRAS-WT was observed.Conclusion
Treatment with PX-866 and docetaxel was well tolerated, without evidence of overlapping/cumulative toxicity. Further investigation with this combination is justified.
SUBMITTER: Bowles DW
PROVIDER: S-EPMC3778312 | biostudies-literature | 2013 Sep
REPOSITORIES: biostudies-literature
Bowles D W DW Ma W W WW Senzer N N Brahmer J R JR Adjei A A AA Davies M M Lazar A J AJ Vo A A Peterson S S Walker L L Hausman D D Rudin C M CM Jimeno A A
British journal of cancer 20130813 5
<h4>Background</h4>This phase I, dose-finding study determined the safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), pharmacokinetics, and antitumour activity of PX-866, a phosphatidylinositol 3-kinase inhibitor, combined with docetaxel in patients with incurable solid tumours.<h4>Methods</h4>PX-866 was administered at escalating doses (4-8 mg daily) with docetaxel 75 mg m⁻² intravenously every 21 days. Archived tumour tissue was assessed for potential predictive biomarkers.< ...[more]