Leonard C E, Chan D C, Chou T C, Kumar R, Bunn P A
Department of Radiation Oncology, Swedish Medical Center, Englewood, Colorado 80110, USA.
Cancer Res. 1996 Nov 15;56(22):5198-204.
Squamous cell carcinoma of the head and neck is the fourth most common cancer in the United States, and therapy for very advanced cases is relatively ineffective. Paclitaxel has activity against cancers of the breast, lung, prostate, cervix, and ovary. The activity of paclitaxel for squamous cell carcinoma of the head and neck is less certain, and results of its radiosensitization properties have been variable. The radiation responses of two squamous carcinomas, SCC-9 (oropharynx) and HEP-2 (larynx), were examined to determine the radiosensitizing potential of paclitaxel. In vitro exposures for 24 and 48 h with paclitaxel concentrations of 10(-4) to 6 x 10(-2) microg/ml were followed by irradiation of 0.1-10 Gy. Percent survival was calculated by colony count, and the paclitaxel-radiation interaction was quantitated by the median effect principle and the combination index method of Chou and Talalay. The paclitaxel-radiation combination resulted in multiphasic interactions in both 24 and 48 h paclitaxel pretreatment in SCC-9 and HEP-2 cell lines. In general there was slight synergism [combination index (CI) <1] at low dose-low effect levels (e.g., at a paclitaxel concentration of 0.002 microg/ml or lower and radiation of 0.1-0.3 Gy), moderate antagonism (CI >1) at median dose ranges and strong synergism (CI <<1) at high dose ranges (e.g., at a paclitaxel concentration of 0.012-0.06 microg/ml and radiation doses of 3-10 Gy), especially at a surviving fraction of <0.1, which is therapeutically relevant. The median effect principle and combination index method provided a simple way to quantitate the synergism or antagonism of a paclitaxel-radiation interaction under various conditions. This analysis demonstrated that paclitaxel-radiation synergy exists at doses that are readily achievable in the clinical scenario for both agents and that greater synergy occurred at high dose-high effect levels. These results suggest that the combination of both therapies should be explored further in clinical trials assessing the treatment of squamous cell carcinomas of the head and neck.
头颈部鳞状细胞癌是美国第四大常见癌症，对于非常晚期的病例，治疗效果相对不佳。紫杉醇对乳腺癌、肺癌、前列腺癌、宫颈癌和卵巢癌具有活性。紫杉醇对头颈部鳞状细胞癌的活性尚不确定，其放射增敏特性的结果也不尽相同。研究了两种鳞状细胞癌SCC-9（口咽）和HEP-2（喉）的辐射反应，以确定紫杉醇的放射增敏潜力。用浓度为10(-4)至6×10(-2)微克/毫升的紫杉醇进行24小时和48小时的体外暴露，随后进行0.1 - 10戈瑞的照射。通过集落计数计算存活率，并根据中效原理和Chou与Talalay的联合指数法对紫杉醇与辐射的相互作用进行定量。在SCC-9和HEP-2细胞系中，紫杉醇与辐射的联合在24小时和48小时紫杉醇预处理中均产生了多相相互作用。一般来说，在低剂量 - 低效应水平（例如，紫杉醇浓度为0.002微克/毫升或更低且辐射为0.1 - 0.3戈瑞）时存在轻微协同作用[联合指数（CI）<1]，在中等剂量范围内存在中度拮抗作用（CI >1），在高剂量范围内存在强协同作用（CI <<1）（例如，紫杉醇浓度为0.012 - 0.06微克/毫升且辐射剂量为3 - 10戈瑞），尤其是在存活分数<0.1时，这在治疗上具有相关性。中效原理和联合指数法提供了一种简单的方法来定量在各种条件下紫杉醇与辐射相互作用的协同或拮抗作用。该分析表明，在两种药物的临床应用中都容易达到的剂量下存在紫杉醇与辐射的协同作用，并且在高剂量 - 高效应水平下协同作用更强。这些结果表明，在评估头颈部鳞状细胞癌治疗的临床试验中，应进一步探索两种疗法的联合应用。
