雷替曲塞在晚期结直肠癌治疗中的应用_West China Medical Journal

Authors：

成科 ,  刘继彦

Corresponding author：

刘继彦, Email: 183818128@qq.com

Keywords：

雷替曲塞; 晚期结直肠癌; 药物治疗; 化疗

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【摘要】　近年来，有关晚期结直肠癌治疗的研究有不少进展，但化疗方面除常用的folfox、folfiri、xelox等化疗方案外，可选的化疗药物有限。作为TS抑制剂的雷替曲塞在晚期结直肠的治疗中也显示了一定的价值，其单药有效率与氟尿嘧啶相似，不良反应略有差异。雷替曲塞与奥沙利铂的联合化疗方案疗效较好，特别是在二线治疗中可能优于常规的二线化疗方案。2010年SFDA批准了雷替曲塞在晚期结直肠癌的适应证，为了让肿瘤临床工作者更好地了解该药，现就雷替曲塞治疗晚期结直肠癌的现状和进展做一综述。

Citation： 成科,刘继彦. 雷替曲塞在晚期结直肠癌治疗中的应用. West China Medical Journal, 2010, 25(11): 1996-2000. doi: Copy

1.	孙燕, 石元凯. 临床肿瘤内科手册[M]. 5版. 北京: 人民卫生出版社, 2007: 491-526.
2.	Grothey A, Sargent D, Goldberg RM, et al. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment[J]. J Clin Oncol, 2004, 22(7): 1209-1214.
3.	Jackman AL, Kimbell R, Ford HE. Combination of raltitrexed with other cytotoxic agent: rationale and preclinical observations[J]. Eur J Cancer, 1999, 35(Suppl 1): 3-8.
4.	Comella P, De Vita F, De Lucia L, et al. Oxaliplatin and raltitrexed combined with leucovorin-modulated 5-fluorouracil i. v bolus every two weeks: a dose finding study in advanced previously treated colorectal carcinoma[J]. Ann Oncol, 2000, 11(4): 461-468.
5.	Wilson KS, Malfair Taylor SC. Raltitrexed: optimism and reality[J]. Expert Opin Drug Metab Toxicol, 2009, 5(11): 1447-1454.
6.	Vakhabova JV, Semenov NN, Dobrova NV, et al. Clinical study of combined use of tomudex (raltitrexed) and xeloda (capecitabine) as first-line treatment for patients with metastasizing colorectal cancer[J]. Bull Exp Biol Med, 2008, 145(2): 249-251.
7.	Cunningham D, Zalcberg JR, Rath U, et al. Final results of a randomised trail comparing ′Tomudex′(raltitrexed) with 5-fluorouracil plus leucovorin in advanced colorectal cancer[J]. Ann Oncol, 1996, 7(9): 961-965.
8.	Cocconi G, Cunningham D, Van Cutsem E, et al. Open, randomized, multicenter trail of raltitrexed versus fluorouracil plus high-dose leucovorin in patients with advanced colorectal cancer. Tomudex Colorectal Cancer Study Group[J]. J Clin Oncol, 1998, 16(9): 2943-2952.
9.	Maughan T, James R, Kerr D, et al. Excess treatment related deaths and impaired quality of life show raltitrexed is inferior to infusional 5-FU regimens in the palliative chemotherapy of advanced colorectal cancer(CRC): Final results of MRC CR06[J]. Ann Oncol, 2000, 11(Suppl 4): 43(Abstr 1850).
10.	Khouri C, Guiu B, Cercueil JP, et al. Raltitrexed and oxaliplatin hepatic arterial infusion for advanced colorectal cancer: a retrospective study[J]. Anticancer Drugs, 2010, 21(6): 656-661.
11.	Scheithauer W, Kornek G, Ulrich-Pur H, et al. Promising therapeutic potential of oxaliplatin + raltitrexed in patients with advanced colorectal cancer (ACC): results of a Phase Ⅰ/Ⅱ trial[J]. Proc Am Soc Clin Oncol, 2000, 19: (Abstr 997).
12.	Douillard JY, Michel P, Gamelin E, et al. Raltitrexed (′Tomudex′) plus oxaliplatin: an active combination for first-line chemotherapy in patients with metastatic colorectal cancer[J]. Proc Am Soc Clin Oncol, 2000, 19: (Abstr 971).
13.	Scheithauer W, Kornek GV, Ulrich-Pur H, et al. Oxaliplatin plus raltitrexed in patients with advanced colorectal carcinoma: results of a Phase I-Ⅱ trial[J]. Cancer, 2001, 91(7): 1264-1271.
14.	Seitz JF, Bennouna J, Paillot B, et al. Multicenter non-randomized phase Ⅱ study of raltitrexed (Tomudex) and oxaliplatin in non-pretreated metastatic colorectal cancer patients[J]. Ann Oncol, 2002, 13(7): 1072-1079.
15.	Scheithauer W, Kornek GV, Schuell B, et al. Second-line treatment with oxaliplatin+raltitrexed in patients with advanced colorectal cancer failing fluoropyrimidine/leucovorin-based chemotherapy[J]. Ann Oncol, 2001, 12(5): 709-714.
16.	Laudani A, Gebbia V, Leonardi V, et al. Activity and toxicity of oxaliplatin plus raltitrexed in 5-fluorouracil refractory metastatic colorectal adeno-carcinoma[J]. Anticancer Res, 2004, 24(2): 1139-1142.
17.	王佳蕾, 李进. 刘天舒. 等. 雷替曲塞或5-FU/CF联合奥沙利铂治疗局部晚期或复发转移性结直肠癌多中心、随机、对照Ⅲ期临床试验[C]. 第十届全国临床肿瘤学大会暨2007年CSCO学术年会中国临床肿瘤学教育专辑, 2007: 335-340.
18.	George P Kim, Daniel J Sargent, Michelle R Mahoney, et al. Phase Ⅲ Noninferiority Trial Comparing Irinotecan With Oxaliplatin, Fluorouracil, and Leucovorin in Patients With Advanced Colorectal Carcinoma Previously Treated With Fluorouracil: N9841[J]. J Clin Oncol, 2009, 27(17): 2848-2854.
19.	Schwartz G, Bertino J, Kemeny N, et al. Phase I trial of sequential raltitrexed (′Tomudex′) followed by 5-FU in patients with advanced colorectal cancer[J]. Proc Am Soc Clin Oncol, 2000, 19: (Abstr 977).
20.	Elomaa P, sterlund P, Virkkunen P, et al. A Phase Ⅰ/Ⅱ dose escalation and tolerability study of raltitrexed combined with carmofur in metastatic colorectal cancer[J]. Proc Am Soc Clin Oncol, 1999, 18: (Abstr 932).
21.	Feliu J, Salud A, Escudero P, et al. Irinotecan plus raltitrexed as first-line treatment in advanced colorectal cancer: a phase Ⅱ study[J]. Br J Cancer, 2004, 90(8): 1502-1507.
22.	Aparicio J, Vicent JM, Maestu I, et al. Multicenter phase Ⅱ trial evaluating a three-weekly schedule of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer[J]. Ann Oncol, 2003, 14(7): 1121-1125.
23.	Aparicio J, Vicent JM, Maestu I, et al. First-line treatment with irinotecan and raltitrexed in metastatic colorectal cancer. Mature results of a multicenter phase Ⅱ study[J]. Oncology, 2005, 68(1): 58-63.
24.	Chiara S, Nobile MT, Tomasello L, et al. Phase Ⅱ trial of irinotecan and raltitrexed in chemotherapy-naive advanced colorectal cancer[J]. Anticancer Res (Br), 2005, 25(2): 1391-1396.
25.	Comella P, Casaretti R, Crucitta E. Oxaliplatin plus raltitrexed and leucovorin-modulated 5-fluorouracil i. v. bolus: a salvage regimen for colorectal cancer patients[J]. Br J Cancer, 2002 17, 86(12): 1871-1875.
26.	Maroun JA, Jonker D, Seymour L, et al. A National Cancer Institute of Canada Clinical Trials Group Study--IND. 135: Phase Ⅰ/Ⅱ study of irinotecan (camptosar), oxaliplatin and raltitrexed (tomudex) (COT) in patients with advanced colorectal cancer[J]. Eur J Cancer, 2006, 42(2): 193-199.
27.	Gambacorta MA, Valentini V, Morganti AG, et al. Chemoradiation with raltitrexed (Tomudex) in preoperative treatment of stage Ⅱ-Ⅲ resectable rectal cancer: a phase Ⅱ study[J]. Int J Radiat Oncol Biol Phys, 2004, 60(1): 130-138.
28.	Teicher BA, Ara G, Chen YN, et al. Interaction of tomudex with radiation in vitro and in vivo[J]. Int J Oncol, 1998, 13(3): 437-442.
29.	Yoney A, Askaroglu B, Hancilar T, et al. A retrospective comparison of concurrent bolus 5-fluorouracil or raltitrexed in preoperative chemoradiation for locally advanced rectal cancer[J]. Hematol Oncol Stem Cell Ther, 2008, 1(1): 28-33.
30.	Gambacorta MA, Valentini V, Coco C, et al. Chemoradiation with raltitrexed and oxaliplatin in preoperative treatment of stage Ⅱ-Ⅲ resectable rectal cancer: phase I and Ⅱ studies[J]. Int J Radiat Oncol Biol Phys, 2004, 60(1): 139-148.
31.	Valentini V, Coco C, Minsky BD, et al. Randomized, multicenter, phase Ⅱb study of preoperative chemoradiotherapy in T3 mid-distal rectal cancer: raltitrexed + oxaliplatin+radiotherapy versus cisplatin+5-fluorouracil+radiotherapy[J]. Int J Radiat Oncol Biol Phys, 2008, 70(2): 403-412.
32.	Avallone A, Delrio P, Pecori B, et al. Oxaliplatin plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy for locally advanced rectal carcinoma: long-term Outcome[J/OL]. Int J Radiat Oncol Biol Phys, 2010, 14: [2010-05-14]. http: //linkingbub. elsevier. com/retrieve/pii/s0360-3016(09)03616-5.
33.	Popov I, Carrato A, Sobrero A, et al. Raltitrexed (Tomudex) versus standard leucovorin-modulated bolus 5-fluorouracil: results from the randomised phase Ⅲ Pan-European Trial in Adjuvant Colon Cancer 01 (PETACC-1)[J]. Eur J Cancer, 2008, 44(15): 2204-2211.

1. 　孙燕, 石元凯. 临床肿瘤内科手册[M]. 5版. 北京: 人民卫生出版社, 2007: 491-526.
2. 　Grothey A, Sargent D, Goldberg RM, et al. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment[J]. J Clin Oncol, 2004, 22(7): 1209-1214.
3. 　Jackman AL, Kimbell R, Ford HE. Combination of raltitrexed with other cytotoxic agent: rationale and preclinical observations[J]. Eur J Cancer, 1999, 35(Suppl 1): 3-8.
4. 　Comella P, De Vita F, De Lucia L, et al. Oxaliplatin and raltitrexed combined with leucovorin-modulated 5-fluorouracil i. v bolus every two weeks: a dose finding study in advanced previously treated colorectal carcinoma[J]. Ann Oncol, 2000, 11(4): 461-468.
5. 　Wilson KS, Malfair Taylor SC. Raltitrexed: optimism and reality[J]. Expert Opin Drug Metab Toxicol, 2009, 5(11): 1447-1454.
6. 　Vakhabova JV, Semenov NN, Dobrova NV, et al. Clinical study of combined use of tomudex (raltitrexed) and xeloda (capecitabine) as first-line treatment for patients with metastasizing colorectal cancer[J]. Bull Exp Biol Med, 2008, 145(2): 249-251.
7. 　Cunningham D, Zalcberg JR, Rath U, et al. Final results of a randomised trail comparing ′Tomudex′(raltitrexed) with 5-fluorouracil plus leucovorin in advanced colorectal cancer[J]. Ann Oncol, 1996, 7(9): 961-965.
8. 　Cocconi G, Cunningham D, Van Cutsem E, et al. Open, randomized, multicenter trail of raltitrexed versus fluorouracil plus high-dose leucovorin in patients with advanced colorectal cancer. Tomudex Colorectal Cancer Study Group[J]. J Clin Oncol, 1998, 16(9): 2943-2952.
9. 　Maughan T, James R, Kerr D, et al. Excess treatment related deaths and impaired quality of life show raltitrexed is inferior to infusional 5-FU regimens in the palliative chemotherapy of advanced colorectal cancer(CRC): Final results of MRC CR06[J]. Ann Oncol, 2000, 11(Suppl 4): 43(Abstr 1850).
10. 　Khouri C, Guiu B, Cercueil JP, et al. Raltitrexed and oxaliplatin hepatic arterial infusion for advanced colorectal cancer: a retrospective study[J]. Anticancer Drugs, 2010, 21(6): 656-661.
11. 　Scheithauer W, Kornek G, Ulrich-Pur H, et al. Promising therapeutic potential of oxaliplatin + raltitrexed in patients with advanced colorectal cancer (ACC): results of a Phase Ⅰ/Ⅱ trial[J]. Proc Am Soc Clin Oncol, 2000, 19: (Abstr 997).
12. 　Douillard JY, Michel P, Gamelin E, et al. Raltitrexed (′Tomudex′) plus oxaliplatin: an active combination for first-line chemotherapy in patients with metastatic colorectal cancer[J]. Proc Am Soc Clin Oncol, 2000, 19: (Abstr 971).
13. 　Scheithauer W, Kornek GV, Ulrich-Pur H, et al. Oxaliplatin plus raltitrexed in patients with advanced colorectal carcinoma: results of a Phase I-Ⅱ trial[J]. Cancer, 2001, 91(7): 1264-1271.
14. 　Seitz JF, Bennouna J, Paillot B, et al. Multicenter non-randomized phase Ⅱ study of raltitrexed (Tomudex) and oxaliplatin in non-pretreated metastatic colorectal cancer patients[J]. Ann Oncol, 2002, 13(7): 1072-1079.
15. 　Scheithauer W, Kornek GV, Schuell B, et al. Second-line treatment with oxaliplatin+raltitrexed in patients with advanced colorectal cancer failing fluoropyrimidine/leucovorin-based chemotherapy[J]. Ann Oncol, 2001, 12(5): 709-714.
16. 　Laudani A, Gebbia V, Leonardi V, et al. Activity and toxicity of oxaliplatin plus raltitrexed in 5-fluorouracil refractory metastatic colorectal adeno-carcinoma[J]. Anticancer Res, 2004, 24(2): 1139-1142.
17. 　王佳蕾, 李进. 刘天舒. 等. 雷替曲塞或5-FU/CF联合奥沙利铂治疗局部晚期或复发转移性结直肠癌多中心、随机、对照Ⅲ期临床试验[C]. 第十届全国临床肿瘤学大会暨2007年CSCO学术年会中国临床肿瘤学教育专辑, 2007: 335-340.
18. 　George P Kim, Daniel J Sargent, Michelle R Mahoney, et al. Phase Ⅲ Noninferiority Trial Comparing Irinotecan With Oxaliplatin, Fluorouracil, and Leucovorin in Patients With Advanced Colorectal Carcinoma Previously Treated With Fluorouracil: N9841[J]. J Clin Oncol, 2009, 27(17): 2848-2854.
19. 　Schwartz G, Bertino J, Kemeny N, et al. Phase I trial of sequential raltitrexed (′Tomudex′) followed by 5-FU in patients with advanced colorectal cancer[J]. Proc Am Soc Clin Oncol, 2000, 19: (Abstr 977).
20. 　Elomaa P, sterlund P, Virkkunen P, et al. A Phase Ⅰ/Ⅱ dose escalation and tolerability study of raltitrexed combined with carmofur in metastatic colorectal cancer[J]. Proc Am Soc Clin Oncol, 1999, 18: (Abstr 932).
21. 　Feliu J, Salud A, Escudero P, et al. Irinotecan plus raltitrexed as first-line treatment in advanced colorectal cancer: a phase Ⅱ study[J]. Br J Cancer, 2004, 90(8): 1502-1507.
22. 　Aparicio J, Vicent JM, Maestu I, et al. Multicenter phase Ⅱ trial evaluating a three-weekly schedule of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer[J]. Ann Oncol, 2003, 14(7): 1121-1125.
23. 　Aparicio J, Vicent JM, Maestu I, et al. First-line treatment with irinotecan and raltitrexed in metastatic colorectal cancer. Mature results of a multicenter phase Ⅱ study[J]. Oncology, 2005, 68(1): 58-63.
24. 　Chiara S, Nobile MT, Tomasello L, et al. Phase Ⅱ trial of irinotecan and raltitrexed in chemotherapy-naive advanced colorectal cancer[J]. Anticancer Res (Br), 2005, 25(2): 1391-1396.
25. 　Comella P, Casaretti R, Crucitta E. Oxaliplatin plus raltitrexed and leucovorin-modulated 5-fluorouracil i. v. bolus: a salvage regimen for colorectal cancer patients[J]. Br J Cancer, 2002 17, 86(12): 1871-1875.
26. 　Maroun JA, Jonker D, Seymour L, et al. A National Cancer Institute of Canada Clinical Trials Group Study--IND. 135: Phase Ⅰ/Ⅱ study of irinotecan (camptosar), oxaliplatin and raltitrexed (tomudex) (COT) in patients with advanced colorectal cancer[J]. Eur J Cancer, 2006, 42(2): 193-199.
27. 　Gambacorta MA, Valentini V, Morganti AG, et al. Chemoradiation with raltitrexed (Tomudex) in preoperative treatment of stage Ⅱ-Ⅲ resectable rectal cancer: a phase Ⅱ study[J]. Int J Radiat Oncol Biol Phys, 2004, 60(1): 130-138.
28. 　Teicher BA, Ara G, Chen YN, et al. Interaction of tomudex with radiation in vitro and in vivo[J]. Int J Oncol, 1998, 13(3): 437-442.
29. 　Yoney A, Askaroglu B, Hancilar T, et al. A retrospective comparison of concurrent bolus 5-fluorouracil or raltitrexed in preoperative chemoradiation for locally advanced rectal cancer[J]. Hematol Oncol Stem Cell Ther, 2008, 1(1): 28-33.
30. 　Gambacorta MA, Valentini V, Coco C, et al. Chemoradiation with raltitrexed and oxaliplatin in preoperative treatment of stage Ⅱ-Ⅲ resectable rectal cancer: phase I and Ⅱ studies[J]. Int J Radiat Oncol Biol Phys, 2004, 60(1): 139-148.
31. 　Valentini V, Coco C, Minsky BD, et al. Randomized, multicenter, phase Ⅱb study of preoperative chemoradiotherapy in T3 mid-distal rectal cancer: raltitrexed + oxaliplatin+radiotherapy versus cisplatin+5-fluorouracil+radiotherapy[J]. Int J Radiat Oncol Biol Phys, 2008, 70(2): 403-412.
32. 　Avallone A, Delrio P, Pecori B, et al. Oxaliplatin plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy for locally advanced rectal carcinoma: long-term Outcome[J/OL]. Int J Radiat Oncol Biol Phys, 2010, 14: [2010-05-14]. http: //linkingbub. elsevier. com/retrieve/pii/s0360-3016(09)03616-5.
33. 　Popov I, Carrato A, Sobrero A, et al. Raltitrexed (Tomudex) versus standard leucovorin-modulated bolus 5-fluorouracil: results from the randomised phase Ⅲ Pan-European Trial in Adjuvant Colon Cancer 01 (PETACC-1)[J]. Eur J Cancer, 2008, 44(15): 2204-2211.

West China Medical Journal

雷替曲塞在晚期结直肠癌治疗中的应用

Abstract Full text Figures/Tables Video References Cited by

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