A multicenter phase 1 study of PX-866 and cetuximab in patients with metastatic colorectal carcinoma or recurrent/metastatic squamous cell carcinoma of the head and neck.
Invest New Drugs
; 32(6): 1197-203, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-24916771
ABSTRACT
BACKGROUND:
This phase I, dose-finding study determined the safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), and antitumor activity of PX-866, a phosphatidylinositol 3-kinase inhibitor, combined with cetuximab in patients with incurable colorectal cancer or squamous cell carcinoma of the head and neck.METHODS:
PX-866 was administered at escalating doses (6-8 mg daily) combined with cetuximab given at a 400 mg/m(2) loading dose followed by 250 mg/m(2) weekly. A "3 + 3" study design was used. Prior therapy with anti-EGFR therapies, including cetuximab, was allowed.RESULTS:
Eleven patients were enrolled. The most frequent treatment-emergent adverse event was diarrhea (90.1%), followed by hypomagnesemia (72.2%), vomiting (72.2%), fatigue (54.5%), nausea (54.5%), rash (45.5%) and peripheral edema (40%). No dose limiting toxicities were observed. The RP2D was 8 mg, the same as the single-agent PX-866 MTD. Best responses in 9 evaluable patients were 4 partial responses (44.4%), 4 stable disease (44.4%), and 1 disease progression (11.1%). The median progression free survival was 106 days (range 1-271).CONCLUSION:
Treatment with PX-866 and cetuximab was tolerated with signs of anti-tumor activity. Further development of this combination is warranted.
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Escamosas
/
Neoplasias Colorretais
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Protocolos de Quimioterapia Combinada Antineoplásica
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Neoplasias de Cabeça e Pescoço
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Recidiva Local de Neoplasia
Tipo de estudo:
Clinical_trials
Idioma:
En
Revista:
Invest New Drugs
Ano de publicação:
2014
Tipo de documento:
Article