• 涼山州第一人民醫(yī)院長(zhǎng)安分院腫瘤科（四川西昌，615000）;

【摘要】　目的　 觀察時(shí)辰化學(xué)療法聯(lián)合放射治療對(duì)比常規(guī)化學(xué)療法聯(lián)合放射治療對(duì)鼻咽癌的近期療效及其不良反應(yīng)。　方法　 2006年2月-2010年3月經(jīng)病理學(xué)證實(shí)未接受過化學(xué)療法的38例晚期鼻咽癌患者隨機(jī)分為常規(guī)化學(xué)療法聯(lián)合放射治療組（A組，n=20）和時(shí)辰化學(xué)療法聯(lián)合放射治療組（B組，n=18）。兩組均采用常規(guī)二維放射治療。A組化學(xué)療法方案為順鉑（DDP）80 mg/m2，采用完全水化方案，第1天靜脈滴注；氟尿嘧啶800 mg/（m2?d），第2~6天120 h連續(xù)靜脈滴注。B組時(shí)辰化學(xué)療法采用Melodies多通道編程輸液泵進(jìn)行正弦曲線式時(shí)間調(diào)節(jié)給藥。兩組均為DDP 80 mg/m2，于10:00~22:00給藥，濃度高峰設(shè)定在16:00；氟尿嘧啶800 mg/m2，于22:00~次日10:00給藥，濃度高峰設(shè)定在凌晨4:00。每21天重復(fù)1次，行2~6療程。　結(jié)果　 A組3程化學(xué)療法后有效率（PR）為95%（19/20），全程結(jié)束完全緩解率（complete remission，CR）達(dá)75%（15/20）；B組在2程化學(xué)療法后PR達(dá)100%，全程治療結(jié)束CR達(dá)94.4%（17/18）。兩組不良反應(yīng)主要為遲發(fā)性血小板減少，發(fā)生率分別為35%（7/20）和22.2%（4/18），其他不良反應(yīng)兩組間無明顯差別。　結(jié)論　 時(shí)辰化學(xué)療法聯(lián)合放射治療對(duì)晚期鼻咽癌在減輕化學(xué)療法造成的血小板減少方面有明顯的優(yōu)勢(shì)，值得臨床推廣應(yīng)用以及進(jìn)一步發(fā)掘時(shí)辰化學(xué)療法在臨床治療的價(jià)值。
【Abstract】　Objective　 To investigate the efficacy and the adverse effects of routine chemotherapy and chrono-chemotherapy combined with radiotherapy for advanced nasopharyngeal cancer patients. 　Methods　 From March 2006 to March 2010, 38 patients diagnosed pathologically to have advanced nasopharyngeal cancer were randomly divided to the routine chemotherapy and radiotherapy group (group A, n=20) and the chrono-chemotherapy and radiotherapy group (group B, n=18). Patients in both groups received bi-dimensional radiotherapy. Patients in group A received a full hydration method, cisplatin (DDP) 80 mg/m2 intravenous infusion was also carried out on day 1; fluorouracil 800 mg/(m2?d) chemotherapy, and 120 hours of continuous intravenous infusion from day 2 to day 6. For patients in group B, Melodies multi-channel infusion pump programming to adjust the time of drug administering with a sinusoidal style was adopted; DDP 80 mg/m2 was administered intravenously on day 1 between 10:00 and 22:00 with the peak concentration set at 16:00; fluorouracil 800 mg/m2 was administered between 22:00 and 10:00 on the next day from day 2 to day 6 with the concentration peak set at 4:00. The treatments in both groups were repeated every 21 days, which was repeated for two to six courses of tremtment.　Results　 After three courses of treatment for group A, partial response (PR) rate was 95% (19/20), and after six courses of treatment, the complete remission (CR) rate was 75% (15/20); After two courses of treatment for group B, the PR rate was 100%, and after six courses of treatment, the CR rate was 94.4% (17/18). The main adverse effect was thrombocytopenia at an incidence rate of 35% (7/20) and 22.4% (4/18) in the two groups respectively. There was no obvious difference in other adverse effects between the two groups.　Conclusion　 Chrono-chemotherapy combined with radiotherapy for advanced nasopharyngeal carcinoma has obvious advantages in reducing thrombocytopenia caused by chemotherapy, and it is worth further exploring the clinical applications and values of chrono-chemotherapy.

引用本文： 邊界. 時(shí)辰化學(xué)療法聯(lián)合放射治療對(duì)鼻咽癌的療效及其不良反應(yīng). 華西醫(yī)學(xué), 2011, 26(4): 510-512. doi: 復(fù)制

1. 　Innominato PF, Lévi FA, Bjarnason GA. Chronotherapy and the molecular clock: Clinical implications in oncology[J]. Adv Drug Deliv Rev, 2010, 62(9-10): 979-1001.
2. 　Bernard S, Cajavec Bernard B, Lévi F, et al. Tumor growth rate determines the timing of optimal chronomodulated treatment schedules[J]. PLoS Comput Biol, 2010, 6(3): e1000712.
3. 　Lévi F, Karaboué A, Gorden L, et al. Cetuximab and circadian chronomodulated chemotherapy as salvage treatment for metastatic colorectal cancer (mCRC): safety, efficacy and improved secondary surgical respectability[J]. Cancer Chemother Pharmacol, 2011, 67(2): 339-348.
4. 　劉泰福, 徐國(guó)鎮(zhèn). 全國(guó)鼻咽癌會(huì)議紀(jì)要[J]. 中華放射腫瘤學(xué)雜志, 1992, 1(4): 204.
5. 　Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada[J]. J Natl Cancer Inst. 2000, 92(3): 205-216.
6. 　黃光武, 鄺國(guó)乾. 實(shí)用鼻咽癌臨床診療學(xué)[M]. 北京: 科學(xué)出版社, 2006, 192-194.
7. 　Liao C, Li J, Bin Q, et al. Chronomodulated chemotherapy versus conventional chemotherapy for advanced colorectal cancer: a meta-analysis of five randomized controlled trials[J]. Int J Colorectal Dis, 2010, 25(3): 343-350.
8. 　Geara FB, Glisson BS, Sanguineti G, et al. Induction chemotherapy followed by radiotherapy versus radiotherapy alone in patients with advanced nasopharyngeal carcinoma: results of a matched cohort study[J]. Cancer, 1997, 79(7): 1279-1286.
9. 　Bouchahda M, Adam R, Giacchetti S, et al. Rescue chemotherapy using multidrug chronomodulated hepatic arterial infusion for patients with heavily pretreated metastatic colorectal cancer[J]. Cancer, 2009, 115(21): 4990-4999.
10. 　楊興龍, 任軍. 時(shí)辰化療聯(lián)合常規(guī)放療對(duì)晚期復(fù)發(fā)轉(zhuǎn)移NPC的療效觀察[J]. 第四軍醫(yī)大學(xué)學(xué)報(bào), 2001, 22(20): 1882-1885.
11. 　郭靈, 林煥新, 邱枋, 等. 5-Fu與DDP時(shí)間調(diào)節(jié)化療治療晚期鼻咽癌的初步臨床觀察[J]. 中國(guó)腫瘤臨床, 2004, 31(13): 721-724.
12. 　金風(fēng), 歐陽金陵, 董紅敏, 等. 鼻咽癌DDP+ 5-Fu/CF方案時(shí)辰化療的臨床前瞻性隨機(jī)研究[J]. 中國(guó)腫瘤臨床, 2004, 31(19): 1123-1125.
  1. 1. 　Innominato PF, Lévi FA, Bjarnason GA. Chronotherapy and the molecular clock: Clinical implications in oncology[J]. Adv Drug Deliv Rev, 2010, 62(9-10): 979-1001.
  2. 2. 　Bernard S, Cajavec Bernard B, Lévi F, et al. Tumor growth rate determines the timing of optimal chronomodulated treatment schedules[J]. PLoS Comput Biol, 2010, 6(3): e1000712.
  3. 3. 　Lévi F, Karaboué A, Gorden L, et al. Cetuximab and circadian chronomodulated chemotherapy as salvage treatment for metastatic colorectal cancer (mCRC): safety, efficacy and improved secondary surgical respectability[J]. Cancer Chemother Pharmacol, 2011, 67(2): 339-348.
  4. 4. 　劉泰福, 徐國(guó)鎮(zhèn). 全國(guó)鼻咽癌會(huì)議紀(jì)要[J]. 中華放射腫瘤學(xué)雜志, 1992, 1(4): 204.
  5. 5. 　Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada[J]. J Natl Cancer Inst. 2000, 92(3): 205-216.
  6. 6. 　黃光武, 鄺國(guó)乾. 實(shí)用鼻咽癌臨床診療學(xué)[M]. 北京: 科學(xué)出版社, 2006, 192-194.
  7. 7. 　Liao C, Li J, Bin Q, et al. Chronomodulated chemotherapy versus conventional chemotherapy for advanced colorectal cancer: a meta-analysis of five randomized controlled trials[J]. Int J Colorectal Dis, 2010, 25(3): 343-350.
  8. 8. 　Geara FB, Glisson BS, Sanguineti G, et al. Induction chemotherapy followed by radiotherapy versus radiotherapy alone in patients with advanced nasopharyngeal carcinoma: results of a matched cohort study[J]. Cancer, 1997, 79(7): 1279-1286.
  9. 9. 　Bouchahda M, Adam R, Giacchetti S, et al. Rescue chemotherapy using multidrug chronomodulated hepatic arterial infusion for patients with heavily pretreated metastatic colorectal cancer[J]. Cancer, 2009, 115(21): 4990-4999.
  10. 10. 　楊興龍, 任軍. 時(shí)辰化療聯(lián)合常規(guī)放療對(duì)晚期復(fù)發(fā)轉(zhuǎn)移NPC的療效觀察[J]. 第四軍醫(yī)大學(xué)學(xué)報(bào), 2001, 22(20): 1882-1885.
  11. 11. 　郭靈, 林煥新, 邱枋, 等. 5-Fu與DDP時(shí)間調(diào)節(jié)化療治療晚期鼻咽癌的初步臨床觀察[J]. 中國(guó)腫瘤臨床, 2004, 31(13): 721-724.
  12. 12. 　金風(fēng), 歐陽金陵, 董紅敏, 等. 鼻咽癌DDP+ 5-Fu/CF方案時(shí)辰化療的臨床前瞻性隨機(jī)研究[J]. 中國(guó)腫瘤臨床, 2004, 31(19): 1123-1125.