CARBOGEN BREATHING WITH NICOTINAMIDE IMPROVES THE OXYGEN STATUS OF TUMORS IN PATIENTS

Nicotinamide and carbogen breathing are both effective radiosensitiser s in experimental tumour models and are even more effective in combina tion. This study was to investigate the feasibility of using the agent s in combination in patients and to measure their effect on tumour oxy genation. Twelve patients with advanced malignant disease were treated with 4-6 g of oral nicotinamide (NCT) in tablet formulation. Ten of t hese 12 patients breathed carbogen (95% oxygen, 5% carbon dioxide) for up to 20 min at presumed peak plasma NCT concentration (C-peak) and h ad tumour oxygen partial pressure (pO(2)) measured using the Eppendorf pO(2)) histograph. The mean C-peak values were 82, 115 and 150 pg ml( -1) for NCT doses of 4, 5 and 6 g respectively and were dose dependent . The time of c(peak) was independent of dose with an overall mean of 2.4 h (range 0.7-4 h). NCT toxicity occurred in 9 out of 12 patients a nd was mild in all but one; carbogen was well tolerated in all patient s. Following NCT only two patients had significant rises (P<0.05) in t umour median pO(2). During carbogen breathing, eight out of ten patien ts had early highly significant rises in pO(2) (P<0.0001), of which si x continued to rise or remained in plateau until completion of gas bre athing. Six patients had hypoxic pretreatment values less than 5 mmHg, which were completely abolished in three and reduced in two during ca rbogen breathing. In conclusion, the combination of NCT and carbogen b reathing was generally well tolerated and gave rise to substantial ris es in tumour pO(2) which were maintained throughout gas breathing. The se results should encourage further study of this potentially useful c ombination of agents as radiosensitisers in the clinic.