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.
Highlights
(Cp,) plasma NCT concentration and had tumour oxygen partial pressure (p02) measured using the Eppendorf pO2) histograph
Combining nicotinamide with carbogen breathing (95% oxygen, 5% carbon dioxide) and accelerated hyperfractionated radiation regimens (ARCON) is one such approach currently being evaluated in Europe
Plasma and urine nicotinamide concentrations were determined using a method of high-performance liquid chromatography (HPLC) analysis based on the procedure descrbed by De Vries and Stratford (De Vries et al, 1980; Stratford et al, 1992)
Summary
Twelve patients were entered into the study, of whom ten received the combination of nicotinamide and carbogen breathing before irradiation and had measurements of tumour pO2 distribution performed. Two patients received nicotinamide alone and were eligible for toxicity and pharmacokinetic asse nt. All had advanced recurrent or metastatic histologically proven malignancy requiring palliative irTadiation, with accessible tumours of an adequate size to obtain a satisfactory number of p02 readings without tissue trauma. Haemorrhagic or too firm for P02 measurements to be performed. Al patients received oral nicotinamide at a dose of 4-6 g as 500 mg tablets (Larkhall Natural Health, UK). Food or drink other than water were alowed after breakfast until completion of carbogen breathing
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
