Journal Title
Title of Journal: Invest New Drugs
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Abbravation: Investigational New Drugs
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Authors: Daniel W Bowles Neil Senzer Diana Hausman Scott Peterson Alex Vo Luke Walker Roger B Cohen Antonio Jimeno
Publish Date: 2014/06/12
Volume: 32, Issue: 6, Pages: 1197-1203
Abstract
Background This phase I dosefinding study determined the safety maximum tolerated dose MTD/recommended phase 2 dose RP2D and antitumor activity of PX866 a phosphatidylinositol 3kinase inhibitor combined with cetuximab in patients with incurable colorectal cancer or squamous cell carcinoma of the head and neck Methods PX866 was administered at escalating doses 6–8 mg daily combined with cetuximab given at a 400 mg/m2 loading dose followed by 250 mg/m2 weekly A “3 + 3” study design was used Prior therapy with antiEGFR therapies including cetuximab was allowed Results Eleven patients were enrolled The most frequent treatmentemergent adverse event was diarrhea 901 followed by hypomagnesemia 722 vomiting 722 fatigue 545 nausea 545 rash 455 and peripheral edema 40 No dose limiting toxicities were observed The RP2D was 8 mg the same as the singleagent PX866 MTD Best responses in 9 evaluable patients were 4 partial responses 444 4 stable disease 444 and 1 disease progression 111 The median progression free survival was 106 days range 1–271 Conclusion Treatment with PX866 and cetuximab was tolerated with signs of antitumor activity Further development of this combination is warranted
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