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. 2001 Sep 1;85(9):1258–1264. doi: 10.1054/bjoc.2001.2036

Oxaliplatin and protracted venous infusion of 5-fluorouracil in patients with advanced or relapsed 5-fluorouracil pretreated colorectal cancer

I Chau 1, A Webb 1, D Cunningham 1, M Hill 1, J S Waters 1, A Norman 2, A Massey 1
PMCID: PMC2375233  PMID: 11720458

Abstract

The purpose of this study was to evaluate the activity and safety of oxaliplatin and protracted venous infusion of 5-fluorouracil (PVI 5-FU) in patients with advanced or relapsed 5-FU pretreated colorectal cancer. 38 patients with advanced or metastatic colorectal carcinoma with documented progression on or within 6 months following 5-FU or thymidylate synthase inhibitor containing chemotherapy were recruited between June 1997 and September 2000. Oxaliplatin (100 mg m−2) was given every 2 weeks and PVI 5-FU (300 mg m−2day−1) was administered. Median age of patients was 61 years. 17 patients had >2 sites of disease involvement. 10 had received 5-FU based adjuvant chemotherapy. 16 received oxaliplatin and PVI 5-FU as second-line chemotherapy for advanced disease and 22 as third or subsequent lines. Median follow up was 6.1 months. The best achieved objective tumour response rate was 29% (11 partial responses 95% confidence interval [CI] = 15–46%). 20 patients (52.6%) had stable disease. The median duration of response was 3.9 months. Even for patients who had previously received both 5-FU and irinotecan (n= 22), 27.3% had partial response with oxaliplatin and PVI 5-FU. 37 patients had symptoms on entry into the study. 25 patients had pain, 10 had anorexia and 28 had lethargy. 64%, 70% and 17.9% had symptomatic improvement after treatment respectively. Grade 3–4 toxicities were anaemia 10.6%, neutropenia 2.6%, thrombocytopenia 5.2%, diarrhoea 18.9%, nausea and vomiting 2.7%, infection 5.4% and lethargy 37.8%. The median survival was 9.1 months. Probability of overall survival at 6 months was 58.4% (95% CI = 38.7–73.7%). The median failure-free survival was 4 months. Oxaliplatin and PVI 5FU is an active and well tolerated regimen in patients with heavily pre-treated advanced colorectal cancer. © 2001 Cancer Research Campaign

Keywords: oxaliplatin, 5-fluorouracil, protracted venous infusion, colorectal carcinoma

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Footnotes

Presented at the 37th Annual Meeting of the American Society of Clinical Oncology, May 2001.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen M., Cunningham D., Schmitt C. The importance of stabilization as an endpoint in the treatment of metastatic colorectal carcinoma: recent quality of life studies. Anticancer Drugs. 1998 Oct;9(9):783–790. doi: 10.1097/00001813-199810000-00007. [DOI] [PubMed] [Google Scholar]
  2. André T., Bensmaine M. A., Louvet C., François E., Lucas V., Desseigne F., Beerblock K., Bouché O., Carola E., Merrouche Y. Multicenter phase II study of bimonthly high-dose leucovorin, fluorouracil infusion, and oxaliplatin for metastatic colorectal cancer resistant to the same leucovorin and fluorouracil regimen. J Clin Oncol. 1999 Nov;17(11):3560–3568. doi: 10.1200/JCO.1999.17.11.3560. [DOI] [PubMed] [Google Scholar]
  3. André 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 Nov;9(11):1251–1253. doi: 10.1023/a:1008475122124. [DOI] [PubMed] [Google Scholar]
  4. Armand J. P., Boige V., Raymond E., Fizazi K., Faivre S., Ducreux M. Oxaliplatin in colorectal cancer: an overview. Semin Oncol. 2000 Oct;27(5 Suppl 10):96–104. [PubMed] [Google Scholar]
  5. Brienza S., Bensmaïne M. A., Soulié P., Louvet C., Gamelin E., François E., Ducreux M., Marty M., André T., de Braud F. Oxaliplatin added to 5-fluorouracil-based therapy (5-FU +/- FA) in the treatment of 5-FU-pretreated patients with advanced colorectal carcinoma (ACRC): results from the European compassionate-use program. Ann Oncol. 1999 Nov;10(11):1311–1316. doi: 10.1023/a:1008319600648. [DOI] [PubMed] [Google Scholar]
  6. Cunningham D., James R. D. Integrating the oral fluoropyrimidines into the management of advanced colorectal cancer. Eur J Cancer. 2001 May;37(7):826–834. doi: 10.1016/s0959-8049(01)00052-1. [DOI] [PubMed] [Google Scholar]
  7. Cunningham D., Pyrhönen S., James R. D., Punt C. J., Hickish T. F., Heikkila R., Johannesen T. B., Starkhammar H., Topham C. A., Awad L. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet. 1998 Oct 31;352(9138):1413–1418. doi: 10.1016/S0140-6736(98)02309-5. [DOI] [PubMed] [Google Scholar]
  8. Fizazi K., Ducreux M., Ruffié P., Bonnay M., Daniel C., Soria J. C., Hill C., Fandi A., Poterre M., Smith M. Phase I, dose-finding, and pharmacokinetic study of raltitrexed combined with oxaliplatin in patients with advanced cancer. J Clin Oncol. 2000 Jun;18(11):2293–2300. doi: 10.1200/JCO.2000.18.11.2293. [DOI] [PubMed] [Google Scholar]
  9. Giacchetti S., Perpoint B., Zidani R., Le Bail N., Faggiuolo R., Focan C., Chollet P., Llory J. F., Letourneau Y., Coudert B. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2000 Jan;18(1):136–147. doi: 10.1200/JCO.2000.18.1.136. [DOI] [PubMed] [Google Scholar]
  10. Glimelius B., Hoffman K., Graf W., Påhlman L., Sjödén P. O. Quality of life during chemotherapy in patients with symptomatic advanced colorectal cancer. The Nordic Gastrointestinal Tumor Adjuvant Therapy Group. Cancer. 1994 Feb 1;73(3):556–562. doi: 10.1002/1097-0142(19940201)73:3<556::aid-cncr2820730310>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  11. Goldwasser F., Gross-Goupil M., Tigaud J. M., Di Palma M., Marceau-Suissa J., Wasserman E., Yovine A., Misset J. L., Cvitkovic E. Dose escalation of CPT-11 in combination with oxaliplatin using an every two weeks schedule: a phase I study in advanced gastrointestinal cancer patients. Ann Oncol. 2000 Nov;11(11):1463–1470. doi: 10.1023/a:1026535824044. [DOI] [PubMed] [Google Scholar]
  12. Gornet J. M., Azoulay D., Lévi F., Yovine A., Misset J. L., Goldwasser F. Dramatic tumor response of bulky liver metastases following treatment with CPT-11 and a chronomodulated 4-day infusion of 5-fluorouracil, folinic acid and oxaliplatin every 2 weeks in a colorectal cancer patient. Anticancer Drugs. 2000 Apr;11(4):263–268. doi: 10.1097/00001813-200004000-00006. [DOI] [PubMed] [Google Scholar]
  13. Graham M. A., Lockwood G. F., Greenslade D., Brienza S., Bayssas M., Gamelin E. Clinical pharmacokinetics of oxaliplatin: a critical review. Clin Cancer Res. 2000 Apr;6(4):1205–1218. [PubMed] [Google Scholar]
  14. Hejna M., Köstler W. J., Raderer M., Tomek S., Brodowicz T., Scheithauer W., Wiltschke C., Zielinski C. C. Phase II study of second-line oxaliplatin, irinotecan and mitomycin C in patients with advanced or metastatic colorectal cancer. Anticancer Drugs. 2000 Sep;11(8):629–634. doi: 10.1097/00001813-200009000-00005. [DOI] [PubMed] [Google Scholar]
  15. Lokich J. J., Ahlgren J. D., Gullo J. J., Philips J. A., Fryer J. G. A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a Mid-Atlantic Oncology Program Study. J Clin Oncol. 1989 Apr;7(4):425–432. doi: 10.1200/JCO.1989.7.4.425. [DOI] [PubMed] [Google Scholar]
  16. Lokich J., Fine N., Perri J., Bothe A., Jr Protracted ambulatory venous infusion of 5-fluorouracil. Am J Clin Oncol. 1983 Feb;6(1):103–107. [PubMed] [Google Scholar]
  17. Lévi F. A., Zidani R., Vannetzel J. M., Perpoint B., Focan C., Faggiuolo R., Chollet P., Garufi C., Itzhaki M., Dogliotti L. Chronomodulated versus fixed-infusion-rate delivery of ambulatory chemotherapy with oxaliplatin, fluorouracil, and folinic acid (leucovorin) in patients with colorectal cancer metastases: a randomized multi-institutional trial. J Natl Cancer Inst. 1994 Nov 2;86(21):1608–1617. doi: 10.1093/jnci/86.21.1608. [DOI] [PubMed] [Google Scholar]
  18. Lévi F., Zidani R., Brienza S., Dogliotti L., Perpoint B., Rotarski M., Letourneau Y., Llory J. F., Chollet P., Le Rol A. A multicenter evaluation of intensified, ambulatory, chronomodulated chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin as initial treatment of patients with metastatic colorectal carcinoma. International Organization for Cancer Chronotherapy. Cancer. 1999 Jun 15;85(12):2532–2540. doi: 10.1002/(sici)1097-0142(19990615)85:12<2532::aid-cncr7>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  19. Lévi F., Zidani R., Misset J. L. Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. International Organization for Cancer Chronotherapy. Lancet. 1997 Sep 6;350(9079):681–686. doi: 10.1016/s0140-6736(97)03358-8. [DOI] [PubMed] [Google Scholar]
  20. Machover D., Diaz-Rubio E., de Gramont A., Schilf A., Gastiaburu J. J., Brienza S., Itzhaki M., Metzger G., N'Daw D., Vignoud J. 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 Jan;7(1):95–98. doi: 10.1093/oxfordjournals.annonc.a010489. [DOI] [PubMed] [Google Scholar]
  21. Maindrault-Goebel F., Louvet C., André T., Carola E., Lotz J. P., Molitor J. L., Garcia M. L., Gilles-Amar V., Izrael V., Krulik M. Oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX6). GERCOR. Eur J Cancer. 1999 Sep;35(9):1338–1342. doi: 10.1016/s0959-8049(99)00149-5. [DOI] [PubMed] [Google Scholar]
  22. Maindrault-Goebel F., de Gramont A., Louvet C., André T., Carola E., Mabro M., Artru P., Gilles V., Lotz J. P., Izrael V. High-dose intensity oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX 7). Eur J Cancer. 2001 May;37(8):1000–1005. doi: 10.1016/s0959-8049(01)00068-5. [DOI] [PubMed] [Google Scholar]
  23. Martoni A., Mini E., Pinto C., Nobili S., Gentile A. L., Dentico P., Angelelli B., Scicolone S., Piana E., Mazzei T. Oxaliplatin and protracted continuous 5-fluorouracil infusion in patients with pretreated advanced colorectal carcinoma. Ann Oncol. 2001 Apr;12(4):519–524. doi: 10.1023/a:1011103213297. [DOI] [PubMed] [Google Scholar]
  24. Miller A. B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  25. Rougier P., Van Cutsem E., Bajetta E., Niederle N., Possinger K., Labianca R., Navarro M., Morant R., Bleiberg H., Wils J. Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet. 1998 Oct 31;352(9138):1407–1412. doi: 10.1016/S0140-6736(98)03085-2. [DOI] [PubMed] [Google Scholar]
  26. Scheithauer W., Kornek G. V., Ulrich-Pur H., Penz M., Raderer M., Salek T., Haider K., Kwasny W., Depisch D. Oxaliplatin plus raltitrexed in patients with advanced colorectal carcinoma: results of a Phase I-II trial. Cancer. 2001 Apr 1;91(7):1264–1271. doi: 10.1002/1097-0142(20010401)91:7<1264::aid-cncr1127>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  27. Van Cutsem E., Cunningham D., Ten Bokkel Huinink W. W., Punt C. J., Alexopoulos C. G., Dirix L., Symann M., Blijham G. H., Cholet P., Fillet G. Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU). Eur J Cancer. 1999 Jan;35(1):54–59. doi: 10.1016/s0959-8049(98)00353-0. [DOI] [PubMed] [Google Scholar]
  28. Wasserman E., Cuvier C., Lokiec F., Goldwasser F., Kalla S., Méry-Mignard D., Ouldkaci M., Besmaine A., Dupont-André G., Mahjoubi M. Combination of oxaliplatin plus irinotecan in patients with gastrointestinal tumors: results of two independent phase I studies with pharmacokinetics. J Clin Oncol. 1999 Jun;17(6):1751–1759. doi: 10.1200/JCO.1999.17.6.1751. [DOI] [PubMed] [Google Scholar]
  29. de Gramont A., Figer A., Seymour M., Homerin M., Hmissi A., Cassidy J., Boni C., Cortes-Funes H., Cervantes A., Freyer G. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000 Aug;18(16):2938–2947. doi: 10.1200/JCO.2000.18.16.2938. [DOI] [PubMed] [Google Scholar]
  30. de Gramont A., Vignoud J., Tournigand C., Louvet C., André T., Varette C., Raymond E., Moreau S., Le Bail N., Krulik M. Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer. Eur J Cancer. 1997 Feb;33(2):214–219. doi: 10.1016/s0959-8049(96)00370-x. [DOI] [PubMed] [Google Scholar]

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