BACKGROUND: Non small cell lung cancers (NSCLC) are rapidly proliferating tumours, which are characterized by the presence of extensive hypoxic components, especially in patients with advanced loco-regional disease. Previous studies suggest a deleterious impact of acute (perfusion-limited) hypoxia on the outcome of radiotherapy for these tumours. AIM: This pilot study was aimed at determining the feasibility and tumour response rates that can be achieved with an ARCON regime in patients with locally advanced, staged IIIA or B, NSCLC tumours. METHODS: The phase I/II study included three steps: accelerated fractionation (AF) combined with carbogen (ten analysable patients), AF together with the daily administration of nicotinamide (n = 11 ) and AF with both carbon and nicotinamide (n = 14). Radiotherapy was based on a large daily dose per fraction (2.75 Gy up to 55 Gy in 4 weeks). Nicotinamide was administered at a dose of 6 g per patient per treatment day and carbogen was inhaled for 5 min before and during radiotherapy. RESULTS: The incidence of grade 3 + acute toxicity during the irradiation did not exceed 10%, neither in the lung parenchyma nor in the mediastinum. No significant difference was found in loco-regional, radio-induced toxicity among the three study steps. Although a similar fraction of patients showed grade 2 or 3 emesis in all the steps, of the 25 patients entered in the two Nicotinamide containing steps 10 (40%) developed grade 2 or greater reactions which significantly detracted from their quality of life. There was no significant difference in tumour clearance rate among the three steps. The percentage of objective responses at 2 months was 60, 54 and 57% in steps 1, 2 and 3, respectively. CONCLUSION: The feasibility of this ARCON protocol, using 2.75 Gy doses per fraction over 4 weeks, is good as regards radiotherapy-related side effects but it appears necessary in future to reduce the dose of Nicotinamide to reduce the incidence of nausea and vomiting. There was no significant difference in time to progression among the three study steps.
BACKGROUND:Non small cell lung cancers (NSCLC) are rapidly proliferating tumours, which are characterized by the presence of extensive hypoxic components, especially in patients with advanced loco-regional disease. Previous studies suggest a deleterious impact of acute (perfusion-limited) hypoxia on the outcome of radiotherapy for these tumours. AIM: This pilot study was aimed at determining the feasibility and tumour response rates that can be achieved with an ARCON regime in patients with locally advanced, staged IIIA or B, NSCLC tumours. METHODS: The phase I/II study included three steps: accelerated fractionation (AF) combined with carbogen (ten analysable patients), AF together with the daily administration of nicotinamide (n = 11 ) and AF with both carbon and nicotinamide (n = 14). Radiotherapy was based on a large daily dose per fraction (2.75 Gy up to 55 Gy in 4 weeks). Nicotinamide was administered at a dose of 6 g per patient per treatment day and carbogen was inhaled for 5 min before and during radiotherapy. RESULTS: The incidence of grade 3 + acute toxicity during the irradiation did not exceed 10%, neither in the lung parenchyma nor in the mediastinum. No significant difference was found in loco-regional, radio-induced toxicity among the three study steps. Although a similar fraction of patients showed grade 2 or 3 emesis in all the steps, of the 25 patients entered in the two Nicotinamide containing steps 10 (40%) developed grade 2 or greater reactions which significantly detracted from their quality of life. There was no significant difference in tumour clearance rate among the three steps. The percentage of objective responses at 2 months was 60, 54 and 57% in steps 1, 2 and 3, respectively. CONCLUSION: The feasibility of this ARCON protocol, using 2.75 Gy doses per fraction over 4 weeks, is good as regards radiotherapy-related side effects but it appears necessary in future to reduce the dose of Nicotinamide to reduce the incidence of nausea and vomiting. There was no significant difference in time to progression among the three study steps.
Authors: Vlad C Sandulache; Yunyun Chen; Heath D Skinner; Tongtong Lu; Lei Feng; Laurence E Court; Jeffrey N Myers; Raymond E Meyn; Clifton D Fuller; James A Bankson; Stephen Y Lai Journal: Mol Cancer Ther Date: 2015-09-16 Impact factor: 6.261
Authors: Lauren J Delaney; Lorela Ciraku; Brian E Oeffinger; Corinne E Wessner; Ji-Bin Liu; Jingzhi Li; Kibo Nam; Flemming Forsberg; Dennis B Leeper; Patrick O'Kane; Margaret A Wheatley; Mauricio J Reginato; John R Eisenbrey Journal: J Ultrasound Med Date: 2019-05-23 Impact factor: 2.153
Authors: Huagang Hou; Ruhong Dong; Jean P Lariviere; Sriram P Mupparaju; Harold M Swartz; Nadeem Khan Journal: J Radiat Res Date: 2011-07-29 Impact factor: 2.724
Authors: John R Eisenbrey; Rawan Shraim; Ji-Bin Liu; Jingzhi Li; Maria Stanczak; Brian Oeffinger; Dennis B Leeper; Scott W Keith; Lauren J Jablonowski; Flemming Forsberg; Patrick O'Kane; Margaret A Wheatley Journal: Int J Radiat Oncol Biol Phys Date: 2018-01-31 Impact factor: 7.038
Authors: Robert J Griffin; Brent W Williams; Nathan A Koonce; John C Bischof; Chang W Song; Rajalakshmi Asur; Meenakshi Upreti Journal: J Oncol Date: 2012-01-04 Impact factor: 4.375