• 四川大學(xué)（成都，610041）1華西臨床醫(yī)學(xué)院MCQ團(tuán)隊(duì)，2華西醫(yī)院胃腸外科中心;

卡培他濱是結(jié)直腸癌化學(xué)治療（化療）方面較好的藥物，在安全性和有效性等方面都顯示了一定程度的優(yōu)越性。其單用效果較好，使用后不良反應(yīng)發(fā)生率低，有希望取代氟尿嘧啶；與奧沙利鉑聯(lián)用有較為滿意的療效，但其與伊立替康聯(lián)用效果有待進(jìn)一步研究。由于患者的個(gè)體差異，具體化療方案的選擇應(yīng)根據(jù)患者情況而定。現(xiàn)對(duì)卡培他濱在結(jié)直腸癌化療中單用與聯(lián)用的應(yīng)用現(xiàn)狀作一綜述，以指導(dǎo)結(jié)直腸癌化療方案的選擇。

引用本文： 郭海艷,劉爽,汪曉東,李立. 卡培他濱在結(jié)直腸癌中單用與聯(lián)用的應(yīng)用現(xiàn)狀. 華西醫(yī)學(xué), 2012, 27(4): 613-616. doi: 復(fù)制

1. 　Law CC, Fu YT, Chau KK, et al. Toxicity profile and efficacy of oral capecitabine as adjuvant chemotherapy for chinese patients with stageⅢ colon cancer[J]. J Dis Colon Rectum 2007, 50(12): 2180-2187.
2. 　Petrioli R, Pascucci A, Francini E, et al. Continuous oral capecitabine at fixed dose in patients older than 75 years with metastatic colorectal and gastric cancer: a study of the multidisciplinary oncology group on gastrointestinal tumors[J]. Anticancer Drugs, 2008, 19(1): 91-96.
3. 　Van Cutsem E, Twelves C, Cassidy J, et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase Ⅲ study[J]. J Clin Oncol, 2001, 19(21): 4097-4106.
4. 　Hoff PM, Ansari R, Batist G, et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase Ⅲ study[J]. J Clin Oncol, 2001, 19(8): 2282-2292.
5. 　Glynne-Jones R, Dunst J, Sebag-Montefiore D, et al. The integration of oral capecitabine into chemoradiation regimens for locally advanced rectal cancer: how successful have we been?[J]. Ann Oncol. 2006, 7(3): 361-371.
6. 　Patt YZ, Lee FC, Liebmann JE, et al. Capecitabine plus 3-weekly irinotecan (XELIRI Regimen) as first-line chemotherapy for metastatic colorectal cancer phaseⅡ trial results[J]. Am J Clin Oncol, 2007, 30(4): 350-357.
7. 　Drewinko B, Yang LY. Cellular basis for the inefficacy of 5-FU in human colon carcinoma[J]. Cancer Treat Rep, 1985, 69(12): 1391-1398.
8. 　Maxwell Summerhayes. Capecitabine: a novel, orally administered, tumour-activated treatment for colorectal cancer[J]. Oncol Pharm Prac, 2001, 7(4): 107-125.
9. 　Smalley SR, Kimler BF, Evans RG, et al. Heterogeneity of 5-fluorouracil radiosensitivity modulation in cultured mammalian cell lines[J]. Int J Radiat Oncol Biol Phys, 1992, 24(3): 519-525.
10. 　秦鑫添, 王希成, 李玉齊, 等. 卡培他濱治療晚期結(jié)直腸癌發(fā)生手足綜合征與療效的觀察[J]. 臨床醫(yī)學(xué)工程, 2011, 18(2): 221-223.
11. 　Van Cutsem E, Hoff PM, Harper P, et al. Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomized, phaseⅢ trials[J]. Br J Cancer, 2004, 90(6): 1190-1197.
12. 　Woynarowski JM, Faivre S, Herzig MC, et al. Oxaliplatin-induced damage of cellularDNA[J]. Mol Pharmacol, 2000, 58(5): 920-927.
13. 　Mathé G, Kidani Y, Triana K, et al. A phaseⅠ trial of trans-1-diaminocyclohexane oxalato-platinum (L-OHP)[J]. Biomed Pharmacother, 1986, 40(10): 372-376.
14. 　Van Cutsem E, Twelves C, Cassidy J, et al. Xeloda Colorectal Cancer Study Group Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phaseⅢ study[J]. J Clin Oncol, 2001, 19(21): 4097-4106.
15. 　Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial[J]. Lancet, 2000, 355(9209): 1041-1047.
16. 　Pfeiffer P, Hahn P, Jensen HA. Short-time infusion of oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) in patients with advanced colorectal cancer[J]. Acta Oncol, 2003, 42(8): 832-836.
17. 　梁堃, 李云峰. 卡培他濱聯(lián)合奧沙利鉑治療老年晚期大腸癌療效觀察[J]. 現(xiàn)代腫瘤醫(yī)學(xué), 2008, 16(8): 1365-1366.
18. 　Kakolyris S, Souglakos J, Polyzos A, et al. Modified CAPOX (capecitabine plus oxaliplatin) regimen every two weeks as second-line treatment in patients with advanced colorectal cancer previously treated with irinotecan-based frontline therapy[J]. Oncology, 2008, 74(1-2): 31-36.
19. 　Santini D, Vincenzi B, La Cesa A, et al. Continuous infusion of oxaliplatin plus chronomodulated capecitabine in 5-fluorouracil and irinotecan resistant advanced colorectal cancer patients[J]. Oncology, 2005, 69(1): 27-34.
20. 　Seymour MT. Group UNCCS: Fluorouracil, oxaliplatin and CPT-11 (irinotecan), use and sequencing(MRC FOCUS): A 2135-patient randomized trial in advanced colorectal cancer(ACRC) [J]. J Clin Oncol, 2005, 23(4): 16.
21. 　Waddell T, Gollins S, Soe W, et al. PhaseⅡ study of short-course capecitabine plus oxaliplatin (XELOX) followed by maintenance capecitabine in advanced colorectal cancer: XelQuali study[J]. Cancer Chemother Pharmacol, 67(5): 1111-1117.
22. 　Krishnamurthi SS, Brell JM., Hoppel CL, et al. PhaseⅠ clinical and pharmacokinetic study of oxaliplatin, irinotecan and capecitabine[J]. Cancer Chemother Pharmacol, 2009, 63(3): 441-450.
23. 　Cathomas R, Köberle D, Ruhstaller T, et al. Heated (37°C) oxaliplatin infusion in combination with capecitabine for metastatic colorectal carcinoma: can it reduce neuropathy?[J]. Support Care Cancer, 2010, 18(10): 1263-1270.
24. 　Kunimoto T, Nitta K, Tanaka T, et al. Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camp-tothecin, a novel water-soluble derivative of camptothecin, against murine tumors[J]. Cancer Res, 1987, 47(22): 5944-5947.
25. 　Fuchs C, Marshall J, Mitchell E, et al. Randomized, controlled trial of irinotecan plus infusional, bolus or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C study[J]. J Clin Oncol, 2008, 26(4): 689-690.
26. 　Park SH, Bang SM, Cho EK, et al. First-Line Chemotherapy with Irinotecan plus Capecitabine for Advanced Colorectal Cancer[J]. Oncology Oncology, 2004, 66(5): 353-357.
27. 　Fuchs CS, MooreMR, H arker G, et al. PhaseⅢ comparison of two irinotecan dos ing regimens in second-line therapy of metastatic colorectal cancer[J]. Clin Oncol, 2003, 21(5): 807-814.
28. 　Zhang A, Xing Q, Q in S, et al. Intra-ethnic differences in genetic variants of the UGT-glucuronosyl transferase 1A1 gene in Chinese populations[J]. Pharmacogenomics J, 2007, 7(5): 333-338.
29. 　耿梅, 馬韜, 徐昊平, 等. 伊立替康聯(lián)合卡培他濱二線治療38例晚期結(jié)直腸癌的臨床觀察[J]. 現(xiàn)代腫瘤醫(yī)學(xué), 2009, 17(7): 1305-1307.
30. 　Cassidy J, Clarke S, Diaz-Rubio E, et al. XELOX vs FOLFOX4: efficacy results from XELOX-1/NO16966, a randomized phase Ⅲ trial in first-line metastatic colorectal cancer (MCRC)[J]. J Clin Oncol, 2007, 25(18): 4030.
31. 　Kakolyris S, Souglakos J, Polyzos A, et al. Modified CAPOX (capecitabine plus oxaliplatin) regimen every two weeks as second-line treatment in patients with advanced colorectal cancer previously treated with irinotecan-based frontline therapy: a multicenter phase Ⅱ study[J]. Oncology, 2008, 74(1-2): 31-36.
32. 　Zarate R, Rodriguez J, Bandres E, et al. Oxaliplatin, irinotecan and capecitabine as first-line therapy in metastatic colorectal cancer (mCRC): a dose-finding study and pharmacogenomic analysis[J]. Br J Cancer, 2010, 102(6): 987-994.
33. 　Chong G, Dickson JL, Cunningham D, et al. Capecitabine and mitomycin C as third-line therapy for patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan[J]. Br J Cancer, 2005, 93(5): 510-514.
34. 　Popov I, Tarabar D, Jovanovi? D, et al. Efficacy and safety of bevacizumab in combination with oxaliplatin, irinotecan and fluoropyrimidine-based therapy in adcanced colorectal cancer[J]. Arch Oncol, 2007, 15(1-2): 10-14.
35. 　Wong A, Nowacki MP, Abt M, et al. Capecitabine as adjuvant treatment for stageⅢ colon cancer[J]. N Engl J Med, 2005, 4(5): 315-323.
36. 　Cassidy J, Douillard JY, Twelves C, et al. Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes’ C colon cancer: the X-ACT trial[J]. Br J Cancer, 2006, 94(8): 1122-1129.
37. 　Leonard GD, Brenner B, Kemeny NE, et al. Neoadjuvant chemotherapy before liver resection for patients with unresectable liver metastases from colorectal carcinoma[J]. J Clin Oncol, 2005, 171(66): 121-246.
38. 　Chau I, Brown G, Cunningham D, et al. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance[J]. J Clin Oncol, 2006, 24(4): 668-672.
39. 　徐志巧, 李寧, 帖曉靜, 等. 奧沙利鉑和希羅達(dá)或醛氫葉酸等治療結(jié)直腸癌研究[J]. 醫(yī)藥論壇雜志, 2007, 28(8): 59-60.
  1. 1. 　Law CC, Fu YT, Chau KK, et al. Toxicity profile and efficacy of oral capecitabine as adjuvant chemotherapy for chinese patients with stageⅢ colon cancer[J]. J Dis Colon Rectum 2007, 50(12): 2180-2187.
  2. 2. 　Petrioli R, Pascucci A, Francini E, et al. Continuous oral capecitabine at fixed dose in patients older than 75 years with metastatic colorectal and gastric cancer: a study of the multidisciplinary oncology group on gastrointestinal tumors[J]. Anticancer Drugs, 2008, 19(1): 91-96.
  3. 3. 　Van Cutsem E, Twelves C, Cassidy J, et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase Ⅲ study[J]. J Clin Oncol, 2001, 19(21): 4097-4106.
  4. 4. 　Hoff PM, Ansari R, Batist G, et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase Ⅲ study[J]. J Clin Oncol, 2001, 19(8): 2282-2292.
  5. 5. 　Glynne-Jones R, Dunst J, Sebag-Montefiore D, et al. The integration of oral capecitabine into chemoradiation regimens for locally advanced rectal cancer: how successful have we been?[J]. Ann Oncol. 2006, 7(3): 361-371.
  6. 6. 　Patt YZ, Lee FC, Liebmann JE, et al. Capecitabine plus 3-weekly irinotecan (XELIRI Regimen) as first-line chemotherapy for metastatic colorectal cancer phaseⅡ trial results[J]. Am J Clin Oncol, 2007, 30(4): 350-357.
  7. 7. 　Drewinko B, Yang LY. Cellular basis for the inefficacy of 5-FU in human colon carcinoma[J]. Cancer Treat Rep, 1985, 69(12): 1391-1398.
  8. 8. 　Maxwell Summerhayes. Capecitabine: a novel, orally administered, tumour-activated treatment for colorectal cancer[J]. Oncol Pharm Prac, 2001, 7(4): 107-125.
  9. 9. 　Smalley SR, Kimler BF, Evans RG, et al. Heterogeneity of 5-fluorouracil radiosensitivity modulation in cultured mammalian cell lines[J]. Int J Radiat Oncol Biol Phys, 1992, 24(3): 519-525.
  10. 10. 　秦鑫添, 王希成, 李玉齊, 等. 卡培他濱治療晚期結(jié)直腸癌發(fā)生手足綜合征與療效的觀察[J]. 臨床醫(yī)學(xué)工程, 2011, 18(2): 221-223.
  11. 11. 　Van Cutsem E, Hoff PM, Harper P, et al. Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomized, phaseⅢ trials[J]. Br J Cancer, 2004, 90(6): 1190-1197.
  12. 12. 　Woynarowski JM, Faivre S, Herzig MC, et al. Oxaliplatin-induced damage of cellularDNA[J]. Mol Pharmacol, 2000, 58(5): 920-927.
  13. 13. 　Mathé G, Kidani Y, Triana K, et al. A phaseⅠ trial of trans-1-diaminocyclohexane oxalato-platinum (L-OHP)[J]. Biomed Pharmacother, 1986, 40(10): 372-376.
  14. 14. 　Van Cutsem E, Twelves C, Cassidy J, et al. Xeloda Colorectal Cancer Study Group Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phaseⅢ study[J]. J Clin Oncol, 2001, 19(21): 4097-4106.
  15. 15. 　Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial[J]. Lancet, 2000, 355(9209): 1041-1047.
  16. 16. 　Pfeiffer P, Hahn P, Jensen HA. Short-time infusion of oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) in patients with advanced colorectal cancer[J]. Acta Oncol, 2003, 42(8): 832-836.
  17. 17. 　梁堃, 李云峰. 卡培他濱聯(lián)合奧沙利鉑治療老年晚期大腸癌療效觀察[J]. 現(xiàn)代腫瘤醫(yī)學(xué), 2008, 16(8): 1365-1366.
  18. 18. 　Kakolyris S, Souglakos J, Polyzos A, et al. Modified CAPOX (capecitabine plus oxaliplatin) regimen every two weeks as second-line treatment in patients with advanced colorectal cancer previously treated with irinotecan-based frontline therapy[J]. Oncology, 2008, 74(1-2): 31-36.
  19. 19. 　Santini D, Vincenzi B, La Cesa A, et al. Continuous infusion of oxaliplatin plus chronomodulated capecitabine in 5-fluorouracil and irinotecan resistant advanced colorectal cancer patients[J]. Oncology, 2005, 69(1): 27-34.
  20. 20. 　Seymour MT. Group UNCCS: Fluorouracil, oxaliplatin and CPT-11 (irinotecan), use and sequencing(MRC FOCUS): A 2135-patient randomized trial in advanced colorectal cancer(ACRC) [J]. J Clin Oncol, 2005, 23(4): 16.
  21. 21. 　Waddell T, Gollins S, Soe W, et al. PhaseⅡ study of short-course capecitabine plus oxaliplatin (XELOX) followed by maintenance capecitabine in advanced colorectal cancer: XelQuali study[J]. Cancer Chemother Pharmacol, 67(5): 1111-1117.
  22. 22. 　Krishnamurthi SS, Brell JM., Hoppel CL, et al. PhaseⅠ clinical and pharmacokinetic study of oxaliplatin, irinotecan and capecitabine[J]. Cancer Chemother Pharmacol, 2009, 63(3): 441-450.
  23. 23. 　Cathomas R, Köberle D, Ruhstaller T, et al. Heated (37°C) oxaliplatin infusion in combination with capecitabine for metastatic colorectal carcinoma: can it reduce neuropathy?[J]. Support Care Cancer, 2010, 18(10): 1263-1270.
  24. 24. 　Kunimoto T, Nitta K, Tanaka T, et al. Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camp-tothecin, a novel water-soluble derivative of camptothecin, against murine tumors[J]. Cancer Res, 1987, 47(22): 5944-5947.
  25. 25. 　Fuchs C, Marshall J, Mitchell E, et al. Randomized, controlled trial of irinotecan plus infusional, bolus or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C study[J]. J Clin Oncol, 2008, 26(4): 689-690.
  26. 26. 　Park SH, Bang SM, Cho EK, et al. First-Line Chemotherapy with Irinotecan plus Capecitabine for Advanced Colorectal Cancer[J]. Oncology Oncology, 2004, 66(5): 353-357.
  27. 27. 　Fuchs CS, MooreMR, H arker G, et al. PhaseⅢ comparison of two irinotecan dos ing regimens in second-line therapy of metastatic colorectal cancer[J]. Clin Oncol, 2003, 21(5): 807-814.
  28. 28. 　Zhang A, Xing Q, Q in S, et al. Intra-ethnic differences in genetic variants of the UGT-glucuronosyl transferase 1A1 gene in Chinese populations[J]. Pharmacogenomics J, 2007, 7(5): 333-338.
  29. 29. 　耿梅, 馬韜, 徐昊平, 等. 伊立替康聯(lián)合卡培他濱二線治療38例晚期結(jié)直腸癌的臨床觀察[J]. 現(xiàn)代腫瘤醫(yī)學(xué), 2009, 17(7): 1305-1307.
  30. 30. 　Cassidy J, Clarke S, Diaz-Rubio E, et al. XELOX vs FOLFOX4: efficacy results from XELOX-1/NO16966, a randomized phase Ⅲ trial in first-line metastatic colorectal cancer (MCRC)[J]. J Clin Oncol, 2007, 25(18): 4030.
  31. 31. 　Kakolyris S, Souglakos J, Polyzos A, et al. Modified CAPOX (capecitabine plus oxaliplatin) regimen every two weeks as second-line treatment in patients with advanced colorectal cancer previously treated with irinotecan-based frontline therapy: a multicenter phase Ⅱ study[J]. Oncology, 2008, 74(1-2): 31-36.
  32. 32. 　Zarate R, Rodriguez J, Bandres E, et al. Oxaliplatin, irinotecan and capecitabine as first-line therapy in metastatic colorectal cancer (mCRC): a dose-finding study and pharmacogenomic analysis[J]. Br J Cancer, 2010, 102(6): 987-994.
  33. 33. 　Chong G, Dickson JL, Cunningham D, et al. Capecitabine and mitomycin C as third-line therapy for patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan[J]. Br J Cancer, 2005, 93(5): 510-514.
  34. 34. 　Popov I, Tarabar D, Jovanovi? D, et al. Efficacy and safety of bevacizumab in combination with oxaliplatin, irinotecan and fluoropyrimidine-based therapy in adcanced colorectal cancer[J]. Arch Oncol, 2007, 15(1-2): 10-14.
  35. 35. 　Wong A, Nowacki MP, Abt M, et al. Capecitabine as adjuvant treatment for stageⅢ colon cancer[J]. N Engl J Med, 2005, 4(5): 315-323.
  36. 36. 　Cassidy J, Douillard JY, Twelves C, et al. Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes’ C colon cancer: the X-ACT trial[J]. Br J Cancer, 2006, 94(8): 1122-1129.
  37. 37. 　Leonard GD, Brenner B, Kemeny NE, et al. Neoadjuvant chemotherapy before liver resection for patients with unresectable liver metastases from colorectal carcinoma[J]. J Clin Oncol, 2005, 171(66): 121-246.
  38. 38. 　Chau I, Brown G, Cunningham D, et al. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance[J]. J Clin Oncol, 2006, 24(4): 668-672.
  39. 39. 　徐志巧, 李寧, 帖曉靜, 等. 奧沙利鉑和希羅達(dá)或醛氫葉酸等治療結(jié)直腸癌研究[J]. 醫(yī)藥論壇雜志, 2007, 28(8): 59-60.