A phase I dose escalation and pharmacodynamic study of SU5416 (semaxanib) combined with weekly cisplatin and irinotecan in patients with advanced solid tumors.
Onkologie
; 36(11): 657-60, 2013.
Article
em En
| MEDLINE
| ID: mdl-24192770
ABSTRACT
BACKGROUND:
This phase I study evaluated the safety of SU5416, a potent and selective inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase Flk-1, in combination with weekly cisplatin and irinotecan in patients with advanced solid tumors.METHODS:
The patients received cisplatin 30 mg/m² and irinotecan 50 mg/m² weekly from week 1 to week 4, with SU5416 at either 65 mg/m² (dose level (DL)1) or 85 mg/m² (DL2) twice weekly for 6 weeks (1 cycle). Serial ¹8fluorodeoxyglucose-positron emission tomography (¹8FDG-PET) and ¹5O-H2O-PET scans were obtained.RESULTS:
13 patients were treated (7 on DL1, 6 on DL2); 7 patients completed at least 1 cycle of treatment. 3 patients experienced dose-limiting toxicity (DLT) at DL2 (grade 3 neutropenia and grade 3 thrombocytopenia causing treatment delay, grade 3 nausea/vomiting). No objective responses were observed at DL1, which was determined to be the maximum tolerated dose (MTD). 1 partial response (PR) was observed at DL2. ¹8FDG-PET responses were documented but did not predict response according to the Response Evaluation Criteria in Solid Tumors (RECIST).CONCLUSIONS:
SU5416 at 65 mg/m² twice weekly combined with cisplatin and irinotecan weekly for 4 of 6 weeks is well tolerated but without evidence of clinical activity. ¹8FDG-PET may be a useful pharmacodynamic marker of SU5416 bioactivity but requires additional development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombocitopenia
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Protocolos de Quimioterapia Combinada Antineoplásica
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Neutropenia Febril Induzida por Quimioterapia
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Náusea
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Neoplasias
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article