Effect of nitric-oxide synthesis on tumour blood volume and vascular activity: a phase I study

摘要: Summary Background Nitric oxide has been implicated in tumour angiogenesis and the maintaining of vasodilator tone blood vessels. The vascular effects inhibition nitric-oxide synthesis have not investigated patients with cancer. Methods Seven women 11 men (12 non-small-cell lung cancer, five prostate one cervical cancer) were recruited onto a phase I dose-escalation study received single dose nitric synthase inhibitor, N-nitro-L-arginine (L-NNA). Dose escalation was done by modified Fibonacci scale three at each level, starting 0·1 mg/kg. Changes dynamic contrast-enhanced CT measures relative volume transfer constant (K) measured 1 h 24 after L-NNA administration. Findings In 18 patients, toxic self-limiting cardiovascular changes: had Common Toxicity Criteria version 2.0 grade hypertension; two sinus bradycardia; palpitation. area under curve (AUC) increased linearly from 163 μmol min −1 L mg/kg to 2150 0·9 L-NNA. eight that underwent scanning, decreased treatment (mean 42·9% [range 12·0–62·1]; paired t test p=0·0070), which sustained for up 33·9% 6·5–64·9]; p=0·035). This decrease associated an increase number non-perfused pixels 7·3% (SD 5·5) baseline 25·1% (15·3; p=0·0089) h, 18·2% (12·9; p=0·050) h. There significant correlation between plasma AUC reduction ( r =0·83; p=0·010). Interpretation We shown vivo cancer role supply, we provide early clinical evidence antivascular activity.