Abstract 1408: Nicotine decreases the therapeutic efficacy of radiotherapy and chemoradiotherapy in vivo

Abstract

Abstract Background: Continued tobacco use during cancer treatment has been associated with poor outcome. Nicotine replacement is currently used as a standard of care for smoking cessation in cancer patients; however, prior data demonstrates that nicotine can promote tumor growth and decrease the effectiveness of cancer treatment in vitro. Methods: Athymic nude mice with human H460 lung cancer cell xenografts were stratified into three Groups beginning when tumors reached 5 mm in maximal dimension: control (CON), short term nicotine (STN, 60 ug subcutaneously every other day x 6 days), or long term nicotine (LTN, 60 ug SC every other day until tumor endpoint). Within each Group, mice were further stratified into three Treatments consisting of saline (SAL), radiotherapy (RT, 3 Gy daily x 5 days), or chemoradiotherapy (CRT, RT + concurrent cisplatin intraperitoneally 3 mg/kg daily x 5 days). Tumor volumes were measured and compared between Treatments and Groups (n=10 per Treatment within each Group). This protocol was approved by the Institutional Animal Care and Use Committee at the University of Kentucky. Results: In CON animals, RT (199 uL at day 30) or CRT (100 uL at day 30) significantly prevented tumor regrowth as compared with control SAL animals (864 uL at day 10 requiring euthanasia as per protocol). As expected, CRT was more effective than RT (p<0.05). Nicotine administration alone (STN or LTN) had no effect on tumor growth rate as compared with CON. In contrast, administration of LTN significantly increased tumor regrowth in RT animals (356 uL at day 30, p<0.05) and CRT treated animals (170 uL ad day 30, p<0.05). To eliminate the effects of nicotine on proliferation following completion of RT or CRT, animals were treated with STN. Administration of STN also significantly increased tumor regrowth in RT animals (328 uL at day 30, p<0.05) and CRT animals (176 uL at day 30, p<0.05) with virtually identical regrowth curves as demonstrated for LTN animals. Conclusions: Results demonstrate that nicotine significantly reduces the efficacy of RT and CRT in vivo. Moreover, data suggest that nicotine use during treatment is the primary determinant of decreased therapeutic response. These results may significantly alter current recommendations for smoking cessation in cancer treatment populations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1408.