Perfusion insufficiency and the resultant hypoxia are recognized as important mechanisms of resistance to anticancer therapy. Modification of the tumor microenvironment to increase perfusion and oxygenation of tumors may improve on the efficacy of these treatments. Using laser Doppler probes to measure microregional RBC flux, this study examines the influence of nicotinamide and carbogen on human tumor perfusion. Ten patients with advanced cancers were studied. Nicotinamide (80 mg/kg) was given p.o., and 60 min later, up to six probes were inserted into the tumor. Readings were taken for 1 h, followed by 10 min of carbogen breathing and 10 additional min of breathing room air. Results were compared with those from a similar group of eight control patients who were not given nicotinamide, but who breathed carbogen. In 44 microregions analyzed, 33 (73%) showed perfusion fluctuations of 50% or more, and 20 (44%) by 100% or more. This compared with the control group in whom 62% and 27% of microregions varied by 50% or more and 100% or more, respectively. Perfusion increases outweighed decreases by 30% with nicotinamide and 20% in the controls. On breathing carbogen, patients pretreated with nicotinamide showed an increase in tumor perfusion of 17% at 5 min and 22% at 10 min, compared with only 0% and 1% in the control group. Pretreatment with nicotinamide made little difference to the random blood flow fluctuations seen in controls. However, when carbogen was introduced, tumor perfusion increased compared with the control group. This may have important therapeutic implications by improving response to treatment and allowing better delivery of systemically administered agents.
The Tumor Biology and Radiation Therapy Group at Mount Vernon Hospital is supported by the Cancer Research Campaign (grant SP1989/0203). M. E. B. P. is supported by the Scott of Yews Trust.