A phase I clinical trial of a ribozyme-based angiogenesis inhibitor targeting vascular endothelial growth factor receptor-1 for patients with refractory solid tumors.
Mol Cancer Ther
; 4(6): 948-55, 2005 Jun.
Article
en En
| MEDLINE
| ID: mdl-15956252
ABSTRACT
PURPOSE:
This study intended to determine the maximum tolerated dose, safety, pharmacokinetic variables, clinical response, and pharmacodynamic markers of daily s.c. administration of Angiozyme. PATIENTS ANDMETHODS:
Patients with refractory solid tumors were enrolled in a dose escalation and expanded cohort design. Dose escalation involved cohorts of patients at doses of 10, 30, 100, or 300 mg/m(2)/d for 29 days. A second component enrolled 15 additional patients at a daily dose of 100 mg/m(2). Patients were eligible to continue on therapy until disease progression.RESULTS:
Thirty-one patients were enrolled and 28 were evaluable (range, 29-505 days; median, 89.5 days). A maximum tolerated dose was not defined by toxicity but rather by the maximal deliverable dose of 300 mg/m(2)/d. Grade 1 to 2 injection site reactions were the most common toxicities. One patient in the 300 mg/m(2) group experienced a reversible grade 3 injection site reaction. Angiozyme showed dose-dependent plasma concentrations with good bioavailability. Surrogate markers showed Angiozyme localization in tumor biopsies and a significant increase in serum von Willebrand factor antigen, a marker for endothelial cell dysfunction. Although Angiozyme-reactive antibody production was noted for some patients, no antibody-related adverse events were noted. Seven of 28 (25%) evaluable patients had stable disease for >or =6 months, with the longest treatment duration of > or =16 months. Two patients (nasopharyngeal carcinoma and melanoma) showed minor responses.CONCLUSION:
Angiozyme was well tolerated with satisfactory pharmacokinetic variables for daily s.c. dosing. Results have provided the basis for subsequent clinical trials of this first-of-class biologically targeted therapeutic.
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Banco de datos:
MEDLINE
Asunto principal:
ARN Catalítico
/
Inhibidores de la Angiogénesis
/
Receptor 1 de Factores de Crecimiento Endotelial Vascular
/
Neoplasias
Límite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Mol Cancer Ther
Asunto de la revista:
ANTINEOPLASICOS
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos