Cancer Res Treat.  2011 Jun;43(2):96-101.

A Retrospective Study of First-Line Combination Chemotherapy in Advanced Colorectal Cancer: A Korean Single-Center Experience

• Lee SI
• Park SH
• Lim DH
• Park KW
• Lee J
• Park JO
• Park YS
• Lim HY
• Kang WK

Abstract

PURPOSE
Fluoropyrimidine-based combination chemotherapy, in combination with either oxaliplatin or irinotecan, has demonstrated efficacy and tolerability in treatment of advanced colorectal cancer (ACC).
MATERIALS AND METHODS
Between January 2006 and December 2007, a total of 478 ACC patients were treated with combination chemotherapy in first-line settings. Combination therapies included: 5-fluorouracil, folinic acid plus oxaliplatin (FOLFOX, n=172), 5-fluorouracil, folinic acid plus irinotecan (FOLFIRI, n=95), capecitabine plus oxaliplatin (XELOX, n=155), and capecitabine plus irinotecan (XELIRI, n=56). FOLFOX and FOLFIRI were repeated every 2 weeks, whereas XELOX and XELIRI were repeated every 3 weeks until occurrence of disease progression or unacceptable toxicity, or until a patient chose to discontinue treatment.
RESULTS
The median age was 58 years (range, 19 to 84 years) and the median chemotherapy durations for FOLFOX, FOLFIRI, XELOX, and XELIRI were 4.9, 4.5, 5.7, and 5.4 months, respectively. Combination chemotherapy regimens were generally well tolerated. The estimated median progression-free-survival (PFS) for all patients was 6.8 months (95% confidence interval, 6.3 to 7.3 months). No statistically significant difference in PFS was found among regimens used as first-line chemotherapy. Sixty percent (n=290) of patients received second or further lines of therapy after failure.
CONCLUSION
Fluoropyrimidine-based combination chemotherapy regimens appear to be equally active and tolerable as first-line therapy for ACC.

Keyword

Colonic neoplasms; Chemotherapy; Irinotecan; Oxaliplatin; Capecitabine

MeSH Terms

Antineoplastic Combined Chemotherapy Protocols
Camptothecin
Colonic Neoplasms
Colorectal Neoplasms
Deoxycytidine
Disease Progression
Drug Therapy, Combination
Fluorouracil
Humans
Leucovorin
Organoplatinum Compounds
Retrospective Studies
Antineoplastic Combined Chemotherapy Protocols
Camptothecin
Deoxycytidine
Fluorouracil
Leucovorin
Organoplatinum Compounds

Figure

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  Fig. 1 Progression-free survival. FOLFOX, 5-fluorouracil, folinic acid plus oxaliplatin; FOLFIRI, 5-fluorouracil, folinic acid plus irinotecan; XELOX, capecitabine plus oxaliplatin; XELIRI, capecitabine plus irinotecan.

Reference

1. Won YJ, Sung J, Jung KW, Kong HJ, Park S, Shin HR, et al. Nationwide cancer incidence in Korea, 2003-2005. Cancer Res Treat. 2009; 41:122–131. PMID: 19809561.

2. Glimelius B, Hoffman K, Graf W, Påhlman L, Sjödén PO. The Nordic Gastrointestinal Tumor Adjuvant Therapy Group. Quality of life during chemotherapy in patients with symptomatic advanced colorectal cancer. Cancer. 1994; 73:556–562. PMID: 8299077.

3. Machover D. A comprehensive review of 5-fluorouracil and leucovorin in patients with metastatic colorectal carcinoma. Cancer. 1997; 80:1179–1187. PMID: 9317168.

4. Raymond E, Chaney SG, Taamma A, Cvitkovic E. Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol. 1998; 9:1053–1071. PMID: 9834817.

5. Mullany S, Svingen PA, Kaufmann SH, Erlichman C. Effect of adding the topoisomerase I poison 7-ethyl-10-hydroxycamptothecin (SN-38) to 5-fluorouracil and folinic acid in HCT-8 cells: elevated dTTP pools and enhanced cytotoxicity. Cancer Chemother Pharmacol. 1998; 42:391–399. PMID: 9771954.

6. Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, et al. Irinotecan Study Group. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med. 2000; 343:905–914. PMID: 11006366.

7. Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000; 355:1041–1047. PMID: 10744089.

8. de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000; 18:2938–2947. PMID: 10944126.

9. Twelves C. Can capecitabine replace 5-FU/leucovorin in combination with oxaliplatin for the treatment of advanced colorectal cancer? Oncology (Williston Park). 2002; 16(12 Suppl No 14):23–26. PMID: 12520636.

10. Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, 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 Clin Oncol. 2001; 19:2282–2292. PMID: 11304782.

11. Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001; 19:4097–4106. PMID: 11689577.

12. Díaz-Rubio E, Tabernero J, Gómez-España A, Massutí B, Sastre J, Chaves M, et al. Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic colorectal cancer: final report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial. J Clin Oncol. 2007; 25:4224–4230. PMID: 17548839.

13. Porschen R, Arkenau HT, Kubicka S, Greil R, Seufferlein T, Freier W, et al. Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol. 2007; 25:4217–4223. PMID: 17548840.

14. Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008; 26:2006–2012. PMID: 18421053.

15. Park SH, Bang SM, Cho EK, Baek JH, Oh JH, Im SA, et al. First-line chemotherapy with irinotecan plus capecitabine for advanced colorectal cancer. Oncology. 2004; 66:353–357. PMID: 15331921.

16. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. European Organization for Research and Treatment of Cancer. National Cancer Institute of the United States. National Cancer Institute of Canada. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 2000; 92:205–216. PMID: 10655437.

17. Goldberg RM, Gill S. Recent phase III trials of fluorouracil, irinotecan, and oxaliplatin as chemotherapy for metastatic colorectal cancer. Cancer Chemother Pharmacol. 2004; 54(Suppl 1):S57–S64. PMID: 15309516.

18. Kuebler JP, de Gramont A. Recent experience with oxaliplatin or irinotecan combined with 5-fluorouracil and leucovorin in the treatment of colorectal cancer. Semin Oncol. 2003; 30(4 Suppl 15):40–46. PMID: 14523794.

19. Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004; 22:23–30. PMID: 14665611.

20. Tournigand C, André T, Achille E, Lledo G, Flesh M, Mery-Mignard D, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004; 22:229–237. PMID: 14657227.

21. Grothey A, Sargent D, Goldberg RM, Schmoll HJ. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol. 2004; 22:1209–1214. PMID: 15051767.

22. Borner MM, Schoffski P, de Wit R, Caponigro F, Comella G, Sulkes A, et al. Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur J Cancer. 2002; 38:349–358. PMID: 11818199.

23. Arkenau HT, Arnold D, Cassidy J, Diaz-Rubio E, Douillard JY, Hochster H, et al. Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer: a pooled analysis of randomized trials. J Clin Oncol. 2008; 26:5910–5917. PMID: 19018087.

24. Conroy T, Hebbar M, Bennouna J, Ducreux M, Ychou M, Llédo G, et al. Quality-of-life findings from a randomised phase-III study of XELOX vs FOLFOX-6 in metastatic colorectal cancer. Br J Cancer. 2010; 102:59–67. PMID: 19920832.

25. Ferrara N. Vascular endothelial growth factor as a target for anticancer therapy. Oncologist. 2004; 9(Suppl 1):2–10. PMID: 15178810.