Horsman Michael R, Overgaard Jens
Department of Experimental Clinical Oncology, Aarhus University Hospital, Nørrebrogade 44, Bldg 5, DK-8000 Aarhus C, Denmark.
Radiother Oncol. 2004 Mar;70(3):301-9. doi: 10.1016/j.radonc.2004.01.017.
Accelerated radiation carbogen nicotinamide (ARCON) therapy is generally well tolerated, but some patients experience intolerance to nicotinamide and carbogen (95% O(2)+5% CO(2)). This study investigated the effect of reducing both the nicotinamide dose and carbogen CO(2) content on radiation response.
A C3H mouse mammary carcinoma grown in the right rear foot of female CDF1 was used and treated when at 200 mm(3). Nicotinamide was intraperitoneally injected 20 min prior to irradiation. Carbogen (CO(2) content of either 2 or 5%, balance O(2)) breathing was started 5 min before, and continued during, additional treatments. Radiation was given locally to tissues of restrained non-anaesthetised mice either as a single or fractionated (10 fractions in 12 days) schedule. The endpoints were local tumour control at 90 days, development of moist desquamation 11-23 days after treatment of normal foot skin, or tumour oxygenation measured with the Eppendorf electrode.
The TCD50 values in this tumour following single or fractionated radiation treatment were 52 and 71Gy, respectively. Carbogen (5% CO(2) content) breathing with every radiation treatment in the fractionated schedule significantly (Chi-squared test; P<0.05) enhanced radiation response (ER 1.25). Significant enhancements were also seen with nicotinamide given either as 10x120 mg/kg (ER 1.25), 6x120 mg/kg (ER 1.11) or 10x90 mg/kg (ER 1.18), although the 6x120 schedule was significantly less effective than 10x120. Combining nicotinamide with carbogen resulted in ERs of 1.39-1.44, and these were independent of the nicotinamide treatments. There was also no significant difference in the enhancement of tumour radiation response or improved tumour oxygenation status if the CO(2) content of the gas breathing was varied from 0% (i.e. 100% O(2)) to 2 or 5% (balance O(2)), although a CO(2) content of 2% did give a smaller enhancement of radiation-induced normal skin damage than 5%.
Both the nicotinamide dose, but not the frequency, and carbogen CO(2) content may be reduced in patients experience intolerance without any significant loss of sensitisation.
加速放疗联合卡波金和烟酰胺（ARCON）治疗通常耐受性良好，但部分患者对烟酰胺和卡波金（95%O₂+5%CO₂）不耐受。本研究调查了降低烟酰胺剂量和卡波金中CO₂含量对放疗反应的影响。
使用在雌性CDF1右后足生长的C3H小鼠乳腺癌，肿瘤体积达200mm³时进行治疗。放疗前20分钟腹腔注射烟酰胺。在每次额外治疗前5分钟开始给予卡波金（CO₂含量为2%或5%，其余为O₂）吸入，并在治疗期间持续。对未麻醉的受限小鼠局部组织进行放疗，放疗方案为单次或分次（12天内分10次）照射。观察终点为90天时的局部肿瘤控制、正常足部皮肤治疗后11 - 23天出现湿性脱屑情况，或用Eppendorf电极测量肿瘤氧合情况。
该肿瘤单次或分次放疗后的TCD50值分别为52Gy和71Gy。在分次放疗方案中，每次放疗时给予卡波金（CO₂含量为5%）吸入显著（卡方检验；P<0.05）增强了放疗反应（增强比1.25）。给予烟酰胺10×120mg/kg（增强比1.25）、6×120mg/kg（增强比1.11）或10×90mg/kg（增强比1.18）时也观察到显著增强，尽管6×120mg/kg方案的效果明显低于10×120mg/kg方案。烟酰胺与卡波金联合使用时增强比为1.39 - 1.44，且与烟酰胺治疗方案无关。如果吸入气体的CO₂含量从0%（即100%O₂）变化到2%或5%（其余为O₂），肿瘤放疗反应的增强或肿瘤氧合状态的改善也无显著差异，尽管2%CO₂含量对放疗引起的正常皮肤损伤的增强作用小于5%。
对于不耐受的患者，烟酰胺剂量而非给药频率以及卡波金的CO₂含量均可降低，且不会显著丧失增敏效果。
