| Autor: |
Robert Kozarski, Andrew Mitchell, Roberto Alonzi, Vicky Goh, Peter Hoskin, N. Jane Taylor, Jane Gregory, Ian C Simcock, Kent Yip, Gavin Halbert, David Miles, J. James Stirling, Sam Bosopem |
| Jazyk: |
angličtina |
| Rok vydání: |
2014 |
| Předmět: |
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| ISSN: |
2151-1942 |
| Popis: |
Purpose: To assess the baseline variation in global renal and tumour blood flow, blood volume and extraction fraction, and changes in these parameters related to the acute physiological effects of a single dose of a non selective inhibitor of nitric oxide synthase, L-NNA. Materials & Methods: Ethical approval and informed consent were obtained for this Phase I clinical study. Patients with advanced solid tumours refractory to conventional therapy were recruited and given L-NNA intravenously at two different dose levels. Volumetric perfusion CT scans were carried out at 1, 24, 48 & 72 hours post L-NNA. Blood pressures were taken at regular interval for 6 hours after LNNA. Results: L-NNA was well tolerated by the four patients who received it. Blood flow (BF) and blood volume (BV) in both tumour and kidney were reduced post L-NNA administration (renal BF—20%; renal BV—19.7%; tumour BF—16.9%; tumour BV—18.6%), though the effect was more sustained in tumour vasculature. A negative correlation was found between the change in systemic blood pressure and vascular supply to the tumour within 1 hour following L-NNA (p 0.0001). Differences in response to L-NNA by separate target lesions in the same patient were observed. Conclusion: The differential effect of L-NNA on tumour and renal blood flow, and the absence of any significant toxicity in this small cohort of patients permit further dose escalation of L-NNA in future early phase trials. The predictive value of blood pressure change in relation to the acute effect of L-NNA on tumour vasculature deserves further evaluation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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