title: Carbogen breathing with nicotinamide improves the oxygen status of tumours in patients.
abstract: Nicotinamide and carbogen breathing are both effective radiosensitisers in experimental tumour models and are even more effective in combination. This study was to investigate the feasibility of using the agents in combination in patients and to measure their effect on tumour oxygenation. Twelve patients with advanced malignant disease were treated with 4-6 g of oral nicotinamide (NCT) in tablet formulation. Ten of these 12 patients breathed carbogen (95% oxygen, 5% carbon dioxide) for up to 20 min at presumed peak plasma NCT concentration (Cpeak) and had tumour oxygen partial pressure (pO2) measured using the Eppendorf pO2) histograph. The mean Cpeak values were 82, 115 and 150 micrograms ml-1 for NCT doses of 4, 5 and 6 g respectively and were dose dependent. The time of Cpeak 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 and was mild in all but one; carbogen was well tolerated in all patients. Following NCT only two patients had significant rises (P < 0.05) in tumour median pO2. During carbogen breathing, eight out of ten patients had early highly significant rises in pO2 (P < 0.0001), of which six continued to rise or remained in plateau until completion of gas breathing. Six patients had hypoxic pretreatment values less than 5 mmHg, which were completely abolished in three and reduced in two during carbogen breathing. In conclusion, the combination of NCT and carbogen breathing was generally well tolerated and gave rise to substantial rises in tumour pO2 which were maintained throughout gas breathing. These results should encourage further study of this potentially useful combination of agents as radiosensitisers in the clinic.
authors.affiliation: MRC Unit, Addenbrookes Hospital, Cambridge, UK.
authors.forename: V M
authors.initials: VM
authors.lastname: Laurence
authors.forename: R
authors.initials: R
authors.lastname: Ward
authors.forename: I F
authors.initials: IF
authors.lastname: Dennis
authors.forename: N M
authors.initials: NM
authors.lastname: Bleehen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002245:Carbon Dioxide / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D009536:Niacinamide / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D010100:Oxygen / Q000008:administration & dosage* / Q000032:analysis*; D010313:Partial Pressure; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
chemical_list: D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D009536:Niacinamide; C011700:carbogen; D010100:Oxygen