Cancer Res Treat.  2005 Aug;37(4):212-215.

Oxaliplatin/5-FU without Leucovorin Chemotherapy in Metastatic Colorectal Cancer

• Shim BY
• Lee KM
• Cho HM
• Kim HJ
• Cho HJ
• Yang J
• Kim JG
• Kim HK

Abstract

PURPOSE
Fluorouracil (5-FU) and leucovorin combination therapy have shown synergistic or additive effect against advanced colorectal cancer, but the frequency of mucositis and diarrhea is increased. Most previous studies have used high dose leucovorin (300~500 mg/m2). However, some studies of oxaliplatin and 5-FU with low-dose or high-dose leucovorin in Korea have shown similar response rates. Therefore, we studied the necessity of leucovorin and evaluated the objective tumor response rates and toxicities of a regimen of oxaliplatin and 5-FU without leucovorin every 2 weeks in metastatic colorectal cancer patients. MATERIALS AND METHODS: Twenty-four patients with metastatic colorectal cancer were enrolled between January 2002 and March 2003. Patients received 85 mg/ m2 of oxaliplatin on day 1, a bolus 5-FU 400 mg/m2 on day 1 and a continuous 5-FU infusion at 600 mg/m2/ 22 hours days 1 and 2, every 2 weeks. RESULTS: Of the 24 patients treated, 17 patients received previous 5FU with leucovorin and/or other chemotherapy. Three patients could not be evaluated. Five partial responses were observed with overall response rate of 21% (n=24). Of the previous chemotherapy group (n= 17), 4 partial responses were observed with response rate of 24%. Median overall survival was 18 months (range 4~32 months) and median progression free survival was 4 months (range 2~6 months). This regimen was well tolerated and only 1 grade 3 anemia was observed. CONCLUSION: Oxaliplatin/5-FU combination therapy without leucovorin achieved a relatively high response rate even in patients resistant to the previous 5-FU chemotherapy, and toxicity was minimal.

Keyword

Oxaliplatin; 5-Flurouracil; Colorectal neoplasms

MeSH Terms

Anemia
Colorectal Neoplasms*
Diarrhea
Disease-Free Survival
Drug Therapy*
Fluorouracil
Humans
Korea
Leucovorin*
Mucositis
Fluorouracil
Leucovorin

Reference

1. 2002 Annual report of Korea Central Cancer Registry (published in 2003). Ministry Health and Welfare. Available from URL: http://www.ncc.re.kr.

2. Schmoll HJ, Buchele T, Grothey A, Dempke W. Where do we stand with 5-fluorouracil? Semin Oncol. 1999; 26:589–605. PMID: 10606252.

3. Petrelli N, Douglass HO Jr, Herrera L, Russell D, Stablein DM, Bruckner HW, et al. Gastrointestinal Tumor Study Group. The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. J Clin Oncol. 1989; 7:1419–1426. PMID: 2674331.

4. Doroshow JH, Multhauf P, Leong L, Margolin K, Litchfield T, Akman S, et al. Prospective randomized comparison of fluorouracil versus fluorouracil and high-dose continuous infusion leucovorin calcium for the treatment of advanced measurable colorectal cancer in patients previously unexposed to chemotherapy. J Clin Oncol. 1990; 8:491–501. PMID: 2407810.

5. Rixe O, Ortuzar W, Alvarez M, Parker R, Reed E, Paull K, et al. Oxaliplatin, tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines of the National Cancer Institute's Anticancer Drug Screen panel. Biochem Pharmacol. 1996; 52:1855–1865. PMID: 8951344.

6. Machover D, Diaz-Rubio E, de Gramont A, Schilf A, Gastiaburu JJ, Brienza S, et al. Two consecutive phase II studies of oxaliplatin (L-OHP) for treatment of patients with advanced colorectal carcinoma who were resistant to previous treatment with fluoropyrimidines. Ann Oncol. 1996; 7:95–98. PMID: 9081400.

7. Becouarn Y, Ychou M, Ducreux M, Borel C, Bertheault-Cvitkovic F, Seitz JF, et al. A phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. J Clin Oncol. 1998; 8:2739–2744. PMID: 9704726.

8. Kwon HC, Kim KT, Lee SA, Park JS, Kim SH, Kim JS, et al. Oxaliplatin with biweekly, low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX 4) as first-line therapy for patients with metastatic colorectal cancer. Cancer Res Treat. 2004; 36:115–120.

9. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981; 47:207–214. PMID: 7459811.

10. Poon MA, O'Connell MJ, Moertel CG, Wieand HS, Cullinan SA, Everson LK, et al. Biochemical modulation of flurouracil: Evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. J Clin Oncol. 1989; 7:1407–1418. PMID: 2476530.

11. de Gramont A, Bosset JF, Milan C, Rougier P, Bouche O, Etienne PL, et al. Randomized trial comparing monthly low-dose leucovorin and flurouracil bolus with bimonthly high dose leucovorin and flurouracil bolus plus continuous infusion for advanced colorectal cancer: A Frech intergroup study. J Clin Oncol. 1997; 15:808–815. PMID: 9053508.

12. 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.

13. Levi F, Zidani R, Misset JL. Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. International Organization for Cancer Chronotherapy. Lancet. 1997; 350:681–686. PMID: 9291901.

14. de Gramont A, Vignoud J, Tournigand C, Louvet C, Andre T, Varette C, et al. Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer. Eur J Cancer. 1997; 33:214–219. PMID: 9135491.

15. de Gramont A, Tournigand C, Louvet C, Andre T, Molitor JL, Raymond E, et al. Oxaliplatin, folinic acid and 5-fluorouracil (folfox) in pretreated patients with metastatic advanced cancer. Rev Med Interne. 1997; 18:769–775. PMID: 9500010.

16. Maindrault-Goebel F, Louvet C, Andre T, Carola E, Lotz JP, Molitor JL, et al. Oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX6). Eur J Cancer. 1999; 35:1338–1342. PMID: 10658524.

17. Andre T, Louvet C, Raymond E, Tournigand C, de Gramont A. Bimonthly high-dose leucovorin, 5-fluorouracil infusion and oxaliplatin (FOLFOX3) for metastatic colorectal cancer resistant to the same leucovorin and 5-fluorouracil regimen. Ann Oncol. 1998; 9:1251–1253. PMID: 9862058.

18. Andre T, Bensmaine MA, Louvet C, Francois E, Lucas V, Desseigne F, et al. Multicenter phase II study of bimonthly high-dose leucovorin, fluorouracil infusion, and oxaliplatin for metastatic colorectal cancer resistant to the same leucovorin and flurouracil regimen. J Clin Oncol. 1999; 17:3560–3568. PMID: 10550155.

19. Bae YZ, Jung JH, Moon CH, Kim SH, Kwon HC, Kim JS, et al. A phase II study of oxaliplatin combined with 5-Fluorouracil and leucovorin (Mayo clinic regimen) in 5-Fluororuacil Refractory Colorectal Cancer. Cancer Res Treat. 2002; 34:218–222.

20. Bang SM, Cho EK, Oh JH, Chang HM, Ahn JS, Lee JA, et al. Combination chemotherapy of oxaliplatin, 5-flurouracil, and leucovorin in 5-fluorouracil-pretreated patients with metastatic colorectal cancer. Cancer Res Treat. 2003; 33:414–419.

21. Lee KS, Lee WS, Kim HK, Jeong JY, Heo DS, Bang YJ, et al. A phase II study of oxaliplatin, 5-fluorouracil, and leucovorin in 5-Fluorouracil pretereated metastatic colorectal cancer. J Korean Cancer Assoc. 2001; 33:99–105.

22. Lee JH, Lee JH, Kim TW, Lee KH, Kang YK, Lee JS, et al. Combination of oxaliplatin, fluorouracil, and leucovorin in the treatment of fluoropyrimidine-pretreated patients with metastatic colorectal cancer. J Korean Med Sci. 2001; 16:69–74. PMID: 11289404.