American Journal of Cancer

, Volume 2, Issue 2, pp 111–124 | Cite as

Cost-Effective Strategies in the Management of Advanced Colorectal Cancer

Review Article
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Abstract

After many years of fluorouracil being a standard part of various treatment regimens for patients with advanced or metastatic colorectal cancer, new agents are now available. The purchase costs of these novel agents are higher than for fluorouracil, so the question is whether these options are cost-effective. This review focuses on cost-effectiveness, concentrating mainly on the drug costs that constitute only a small percentage of the overall cost of cancer care, but are a major focus in the planning of healthcare services.

Although new agents tend to have higher purchase costs than fluorouracil, they have other advantages that may render them more cost-effective. Capecitabine achieves higher response rates, equivalent progression-free and overall survival, with a substantially improved tolerability profile compared with fluorouracil. Patients prefer oral treatments and medical resource use is significantly lower with capecitabine than with the Mayo Clinic fluorouracil regimen. Capecitabine may replace single agent fluorouracil therapy as the standard single agent treatment for patients with colorectal cancer.

The administration of raltitrexed is also more convenient than fluorouracil. Patients prefer raltitrexed to fluorouracil regimens and the additional purchase cost of raltitrexed is offset by the decreased incidence of expensive adverse effects and ease of administration. However, since there is no survival benefit, raltitrexed is not cost-effective in terms of life-years gained. The use of raltitrexed may be largely limited to those patients not able to tolerate fluorouracil.

Irinotecan, as combination treatment in the first-line setting with fluorouracil and as a single agent second-line therapy, is associated with significant gains in progression-free and overall survival. There are additional toxicities associated with irinotecan, but they appear not to have an adverse effect on quality of life.

Oxaliplatin with fluorouracil in the first-line setting also extends median progression-free survival. The addition of oxaliplatin may also prolong survival, but this is less clear and it is not yet possible to define the cost per life-year gained compared with fluorouracil alone. The combination treatment allows more patients to undergo resection of liver metastases, improving prospects of long-term survival.

Cost-effectiveness evaluations are increasingly important as novel anticancer treatments emerge competing for limited resources. A single parameter by which to judge cost-effectiveness has not been defined. A standard methodology is needed but even then judgments may vary between countries, tumor types and treatments available, leading to differing priorities.

Notes

Acknowledgments

Dr Chris Twelves has served on Advisory Board for Pharmaceutical Companies and as an expert for NICE.

References

  1. 1.
    Chu KC, Tarone RE, Chow WH, et al. Temporal patterns in colorectal cancer incidence, survival, and mortality from E950 through 1990. J Nati Cancer Inst 1994; 86: 997–1006Google Scholar
  2. 2.
    Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin 1999; 49: 33–64PubMedGoogle Scholar
  3. 3.
    Landis SH, Murray T, Bolden S, et al. Cancer statistics 1999. CA Cancer J Ciin 1999; 49: 8–31Google Scholar
  4. 4.
    Midgley R, Kerr D. Colorectal cancer. Lancet 1999; 353: 391–9PubMedGoogle Scholar
  5. 5.
    Williams NS, Northover JMA, Arnott SJ, et al. Coiorectal tumours. In: Peckham M, Pinedo H, Veronesi U, editors. Oxford textbook of oncology. Oxford: Oxford University Press, 1995: 1133–68Google Scholar
  6. 6.
    Mankiw NG. Principles of economics. Orlando (FL): Dryden Press, 1998Google Scholar
  7. 7.
    Drarnmond MF, O’Brien B, Stoddart GL, et al. Methods for the economic evaluation of health care programmes. 2nd ed. Oxford: Oxford University Press, 1997Google Scholar
  8. 8.
    Mehrez A, Gafni A. Quality-adjusted life-years, utility theory and healthy years equivalents. Med Decis Making 1989; 9: 142–9PubMedGoogle Scholar
  9. 9.
    Wingo PA, Ries LA, Parker SL, et al. Long-term cancer patient survival in the United States. Cancer Epidemiol Biomarkers Prev 1998; 7: 271–82PubMedGoogle Scholar
  10. 10.
    Khayat D, Gil-Delgado M, Antoine EC, et al. The role of Irinotecan and oxaliplatin in the treatment of advanced colorectal cancer. Oncology (Huntingt) 2001 Apr; 15(4): 415–29Google Scholar
  11. 11.
    Hoff PM, Ansar 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 randomised phase III study. J Clin Oncol 2001 Apr 15; 19(8): 2282–92PubMedGoogle Scholar
  12. 12.
    Bomer NM. Neoadjuvant chemotherapy for unresectabie liver metastases of colorectal cancer-too good to be true? Ann Oncol 1999; 10: 623–6Google Scholar
  13. 13.
    Adson MA, Van Heerden JA, Adson MH, et al. Resection of hepatic metastases from colorectal cancer. Arch Surg 1984; 119: 647–51PubMedGoogle Scholar
  14. 14.
    Hughes KS, Simon R, Songhorabodi S, et al. Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence. Surgery 1986; 100: 278–84PubMedGoogle Scholar
  15. 15.
    Schlag P, Hohenberger P, Herfarth C. Resection of liver metastases in colorectal cancer-competitive analysis of treatment results in synchronous versus metachronous metastases. Eur J Surg Oncol 1990; 16: 360–5PubMedGoogle Scholar
  16. 16.
    Doci R, Gennari L, Bignami P, et al. One hundred patients with hepatic metastases from colorectal cancer treated by resection: analysis of prognostic determinants. Br J Surg 1991; 78: 797–801PubMedGoogle Scholar
  17. 17.
    Gayowski T’J, Iwatsuki S, Seiby R, et al. Experience in hepatic resection for metastatic colorectal cancer: analysis of clinical and pathologic risk factors. Surgery 1994; 116: 703–10PubMedGoogle Scholar
  18. 18.
    Scheele J, Stang R, Altendorf-Hofmann A, et al. Resection of colorectal liver metastases. World J Surg 1995; 19: 59–71PubMedGoogle Scholar
  19. 19.
    Fong Y, Blumgart LH, Fortner JG, et al. Pancreatic or liver resection for malignancy is safe and effective for the elderly. Ann Surg 1995; 222: 426–34PubMedGoogle Scholar
  20. 20.
    Nordlinger B, Guignet M, Vaillant JC, et al. Surgicai resection of colorectal carcinoma metastases to the liver: a prognostic scoring system to improve case selection, based on 1568 patients. Cancer 1996; 77: 1254–62PubMedGoogle Scholar
  21. 21.
    Jenkins LT, Millikan KW, Bines SD, et al. Hepatic resection for metastatic colorectal cancer. Am Surg 1997; 63: 605–10PubMedGoogle Scholar
  22. 22.
    Rees M, Plant G, Bygrave S. Late results justify resection for multiple hepatic metastases from colorectal cancer. Br J Surg 1997; 84: 1136–40PubMedGoogle Scholar
  23. 23.
    Jamison RL, Donohue JH, Nagorney DM, et al. Hepatic resection for metastatic colorectal cancer results in cure for some patients. Arch Surg 1997; 132: 505–10PubMedGoogle Scholar
  24. 24.
    Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1000 consecutive cases. Ann Surg 1999; 230: 309–18PubMedGoogle Scholar
  25. 25.
    Rougier P, Milan C, Lazorthes F, et al. Prospective study of prognostic factors in patients with unresected hepatic metastases from colorectal cancer: Fondation Francaise de Cancerologie Digestive. Br J Surg 1995; 82: 1397–400PubMedGoogle Scholar
  26. 26.
    Scheele J, Stangl R, Altendorf-Hofmann A. Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. Br J Surg 1990; 77: 1241–6PubMedGoogle Scholar
  27. 27.
    Stangl R, Altendorf-Hofmann A, Charnley RM, et al. Factors influencing the naturai history of colorectal liver metastases. Lancet 1994; 343: 1405–10PubMedGoogle Scholar
  28. 28.
    Blijham GH. Chemotherapy of colorectal cancer. Anticancer Drugs 1991; 2: 233–45PubMedGoogle Scholar
  29. 29.
    Mayer RJ. Chemotherapy for metastatic colorectal cancer. Cancer 1992; 70(5 Suppl.): 1414–24PubMedGoogle Scholar
  30. 30.
    Benson III AB. Therapy for advanced colorectal cancer. Semin Oncol 1998; 25(11 Suppl.): 2–11PubMedGoogle Scholar
  31. 31.
    Conley BA, Kaplan RS, Arbuck SG. National Cancer Institute clinical triais program in colorectal cancer. Cancer Chemother Pharmacol 1998; 42(7 Suppl.): S75–9PubMedGoogle Scholar
  32. 32.
    Scheithauer W, Rosen M, Kerneck GV. et al. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BMJ 1993; 306: 752–5PubMedGoogle Scholar
  33. 33.
    Advanced Colorectal Cancer Meta-Analysis Project. Modulation of flurouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. J Clin Oncol 1992; 10: 896–903Google Scholar
  34. 34.
    Meta-Analysis Group in Cancer. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 1998; 16: 301–8Google Scholar
  35. 35.
    Caudry M, Bonnel C, Hoquet A, et al. A randomised study of bolus fiuorouracil plus folinic acid versus 21-day fluorouracil infusion aione or in association with cyclophosphamide and mitomycin C in advanced colorectal carcinoma. Am J Clin Oncol 1995; 18: 118–25PubMedGoogle Scholar
  36. 36.
    de Gramont A, Bosset JF, Milan C, et al. Randomised triai comparing monthly low-dose ieucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French Intergroup study. J Clin Oncol 1997; 15: 808–15PubMedGoogle Scholar
  37. 37.
    Lokich JJ, Ahlgren AJ, Gullo JJ, et al. A prospective randomised comparison of continuous infusion fiuorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a mid-Atiantic oncology program study. J Clin Oncol 1989; 7: 425–32PubMedGoogle Scholar
  38. 38.
    Schmoll HJ, Kohne CH, Lorenz M, et al. Weekly 24h infusion of high-dose (HD) 5-fluorouracil (5-FU24h) with or without folinic acid (FA) vs. boius 5-FU/FA (NCCTG/Mayo) in advanced colorectal cancer (CRC): a randomised phase III study of the EORTC GITCCG and the AIO [abstract 935]. Proc Am Soc Clin Oncol 2000; 19: 241aGoogle Scholar
  39. 39.
    Leichman CG, Fleming TR, Muggia FM, et al. Phase II study of fluorouracil and its modulation in advanced colorectal cancer: a Southwest Oncology group Study. J Clin Oncol 1995; 13: 1303–11PubMedGoogle Scholar
  40. 40.
    Topham C, Moore J. Patients preferences for chemotherapy schedules used in the treatment of advanced colorectal cancer: a pilot study. Eur J Cancer Care 1997; 6: 291–4Google Scholar
  41. 41.
    Liu G, Franssen E, Fitch M, et al. Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 1997; 15: 110–5PubMedGoogle Scholar
  42. 42.
    Borner M, Schaffski P, de Wit R, et al. A randomised cross-over triai comparing orai LIFT (uracil/tegafur) + leucovorin (LV) and intravenous fluorouracil (FU) + LV for patient preferences and pharmacokinetic studies in advanced colorectal cancer [abstract 741]. Proc Am Soc Clin Oncol 2000; 19: 191aGoogle Scholar
  43. 43.
    Payne SA. A study of quality of life in cancer patients receiving palliative chemotherapy. Soc Sci Med 1992; 35: 1505–9PubMedGoogle Scholar
  44. 44.
    Demario MD, Ratain MJ. Orai chemotherapy: rationale and future directions. J Clin Oncol 1998; 16: 2557–67PubMedGoogle Scholar
  45. 45.
    Rustum YM, Marstrick A, Cao S, et al. Thyrnidilate synthase inhibitors in cancer therapy: direct and indirect inhibitors. J Clin Oncol 1997; 15: 389–400PubMedGoogle Scholar
  46. 46.
    Punt C. New drags in the treatment of colorectal carcinoma. Cancer 1998; 83: 679–89PubMedGoogle Scholar
  47. 47.
    Ron IG, Lotan A, Inbar MT, et al. Advanced colorectal carcinoma: redefining the role of oral ftorafur. Anticancer Drugs 1996; 7: 649–54PubMedGoogle Scholar
  48. 48.
    Pazdur R, Douillard J-Y, Skiliings JR, et al. Multicenter phase III study of 5-fluorouracil (5-FU) of LIFT™ in combination with leucovorin (LV) in patients with metastatic colorectal cancer [abstract 1009]. Prix Ara Soc Clin Oncol 1999; 18: 263aGoogle Scholar
  49. 49.
    Miwa M, Ura M, Nishida M, et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissues. Eur J Cancer 1998; 8: 1274–81Google Scholar
  50. 50.
    Ishikawa T, Sekiguchi F, Fukase Y, et al. Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumours in human cancer xenografts. Cancer Res 1998; 58: 685–90PubMedGoogle Scholar
  51. 51.
    Van Cutsem E, Findlay M, Osterwalder B, et al. Capecitabine (Xeloda™), an oral fluoropyrimidine carbamate with substantial activity in advanced colorectal cancer: results of a randomised phase II study. J Clin Oncol 2000; 18: 1338–45Google Scholar
  52. 52.
    Van Cutsem E, Twelves C, Cassidy J. et al. Oral capecitabine with metastatic colorectal cancer: results of a large phase II study. J Clin Oncol 2001; 19: 4097–106PubMedGoogle Scholar
  53. 53.
    Twelves C, Boyer M, Findlay M, et al. Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma. Eur J Can 2001 Mar; 37(5): 597–604Google Scholar
  54. 54.
    Meta-Analysis Group in Cancer. Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. J Clin Oncol 1998; 16(11): 3537–41Google Scholar
  55. 55.
    International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) Investigators. Efficacy of adjuvant fluorouracii and folinic acid in colon cancer. Lancet 1995; 345: 939–44Google Scholar
  56. 56.
    Gunasekara NS, Faulds D. Raltitrexed a review of its pharmacological properties and clinical efficacy in the management of advanced colorectal cancer. Drugs 1998; 55: 423–32PubMedGoogle Scholar
  57. 57.
    Summerhayes M. Raltitrexed and the treatment of advanced colorectal cancer. J Oncol Pharm Pract 1996; 2: 225–32Google Scholar
  58. 58.
    Cunningham C. Mature results from three large controlled studies with raltitrexed (“Tomudex”). Br J Cancer 1998; 77Suppl. 2: 15–21PubMedGoogle Scholar
  59. 59.
    Cocconi G, Cunningham D, van Cutsem E, et al. Open, randomised, multicenter trial of raltitrexed versus fluorouracii plus high-dose leucovorin in patients with advanced colorectal cancer. J Clin Oncol 1998; 16: 2943–52PubMedGoogle Scholar
  60. 60.
    Cunningham D, Zalcberg JR, Rath U, et al. Final results of a randomised trial comparing “Tomudex” (raltitrexed) with 5-fluorouracil plus leucovorin in advanced colorectal cancer. Ann Oncol 1996; 7: 961–5PubMedGoogle Scholar
  61. 61.
    Pazdur R, Vincent M. Raltitrexed (Tomudex) versus 5-flourouracil and leucovorin (5-FU + LV in patients with advanced colorectal cancer (ACC): results of a randomised, multi-center, North American trial [abstract 801]. Proc Ara Soc Clin Oncol 1997; 16: 228aGoogle Scholar
  62. 62.
    Groener MGH, van Ineveld BM, Byttebier G, et al. An economic evaluation of Tomudex (raltitrexed) and 5-fiuorouracil plus leucovorin in advanced colorectal cancer. Anticancer Drugs 1999; 10: 283–8PubMedGoogle Scholar
  63. 63.
    Sculpher M, Palmer MK, Heyes A. Costs incurred by patients undergoing advanced colorectal cancer therapy: a comparison of raltitrexed and fluorourail plus folinic acid. Pharmacoeconomics 2000 Apr; 17(4): 361–70PubMedGoogle Scholar
  64. 64.
    Ross P, Heron J, Cunningham D. Cost of treating advanced colorectal cancer: a retrospective comparison of treatment regimen. Eur J Cancer 1996; 32ASuppl. 5: S13–7PubMedGoogle Scholar
  65. 65.
    Summerhayes M, Wanklyn SJ, Shakespeare RA, et al. Reduced pharmacy resource utilisation associated with raltirexed treatment of advanced colorectal cancer. J Oncol Pharm Pract 1997; 3: 13–9Google Scholar
  66. 66.
    Elliot R. An analysis of drug costs for the management of chemotherapy-related side effects in advanced colorectal cancer: a comparison between raltitrexed (“Tomudex”) and 5-fluorouracil plus folinic acid. J Oncol Pharm Pract 1996; 2: 186–90Google Scholar
  67. 67.
    Kerr D, O’Connor KM. An economic comparison of the net clinical benefit and treatment costs of raltitrexed and 5-fluorouracil + leucovorin (Mayo regimen) in advanced colorectal cancer. J Med Econ 1999; 2: 123–32Google Scholar
  68. 68.
    Hale JP, Cohen DR, Maughan TS, et al. Costs and consequences of different chemotherapy regimens in metastatic colorectal cancer. Br J Cancer 2002; 86: 1684–90PubMedGoogle Scholar
  69. 69.
    Maughan TS, James RD, Kerr D, et al. A multicentre randomised trial comparing survival, palliation and quality of life for 3 chemotherapy regimens (de Gramont, Lokich and raltitrexed) in metastatic colorectal cancer. Lancet 2002; 359(9317): 1555–63PubMedGoogle Scholar
  70. 70.
    Young A, Topham C, Moore J, et al. A patient preference study comparing ralititrexed (“Tomudex”) and bolus or infusional 5-fluorouracil regimens in advanced colorectal cancer: influence of side effects and administration attributes. Eur J Cancer Care 1999; 8: 254–61Google Scholar
  71. 71.
    Manning WG, Newhouse JP, Duan N, et al. Health insurance and the demand for medical care: evidence from a randomised experiment. Am Econ Rev 1987; 77: 251–77PubMedGoogle Scholar
  72. 72.
    Torgerson DJ, Donaldson C, Reid DM. Private versus social opportunity cost of time: valuing time in the demand for health care. Health Econ 1994; 3: 149–55PubMedGoogle Scholar
  73. 73.
    de Forni M, Bugrat R, Chabot CG, et al. Phase I and pharmacokinetic study of the camptathecin derivative irinotecan, administered on a weekly schedule in colorectal cancer. Cancer Res 1994; 54: 4347–54PubMedGoogle Scholar
  74. 74.
    Shimada Y, Yoshino M, Wakui A, et al. Phase II study of CPT-11, a new camptothecin derivative, in metastatic colorectal cancer in chemotherapy-naïve patients pretreated with fluorouracil-based chemotherapy. J Clin Oncol 1993; 11: 909–13PubMedGoogle Scholar
  75. 75.
    Rothenberg ML, Cox JV, De Vore RF, et al. A multicenter, phase II trial of weekly irinotecan (CPT-11) in patients with previously treated colorectal carcinoma. Cancer 1999; 85: 786–95PubMedGoogle Scholar
  76. 76.
    Rougier PH, Van Cutsem E, Bajetta E, et al. Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet 1998; 352(9138): 1407–12PubMedGoogle Scholar
  77. 77.
    Cunningham D, Pyrhonen S, James RD, et al. Randomised triai of irinotecan plus supportive care vs supportive care alone after fluorouracii failure for patients with metastatic colorectal cancer. Lancet 1998; 352(9138): 1413–8PubMedGoogle Scholar
  78. 78.
    Bastian G, Grossin F, Benharomouda A, et al. A pharmacokinetic study of CPT-11 and 5-FU combination during a phase I trial [abstract 780]. Proc Am Soc Clin Oncol 1998; 17: 203aGoogle Scholar
  79. 79.
    Benhammouda A, Bastian G, Rixe O, et al. A phase I and pharmacokinetic (PK) study of CPT-11 (C) and 5-FU (F) combination [abstract 710]. Proc Am Soc Clin Oncol 1997; 16: 202aGoogle Scholar
  80. 80.
    Sastre J, Paz-Ares L, Diaz-Rubio E, et al. Phase I dose-finding study of irinotecan (CPT-11) over a short IV infusion combined with a fixed dose of fluorouracil protracted continuous IV infusion in patients with advanced solid tumors [abstract S252]. Eur J Cancer 1997; 33(8): 1141Google Scholar
  81. 81.
    Aranda E, Carrati A, Cervantes A, et al. Phase I/II study of escalating doses of weekly irinotecan (CPT-11) in combination with fluorouracil (5-FU) (48h continuous IV infusion) in patients with advanced solid tumors [abstract 1064]. Proc Am Soc Clin Oncol 1999; 18: 277aGoogle Scholar
  82. 82.
    Huinink WT, Moiseyenko V, Glimelius B, et al. A randomised phase II multicenter trial of irinotecan (CPT-11) using different schedules in patients with metastatic colorectal cancer (MCRC) [abstract 951]. Proc Am Soc Ciin Oncol 2000; 17: 245aGoogle Scholar
  83. 83.
    Van Cutsem E, Pozzo C, Starkharnmar H, et al. A phase II study of irinotecan alternated with 5 days bolus of 5-fluorouracil/leucovorin in first-line chemotherapy of metastatic colorectal cancer. Ann Oncol 1998; 9(11): 1199–204PubMedGoogle Scholar
  84. 84.
    Rothenberg ML, Padzur R, Rowinsky EK, et al. A phase II multicenter trial of alternating cycles of irinotecan (CPT-11) and 5-FU/leucovorin in patients with previously untreated metastatic colorectal cancer [abstract 944]. Proc Am Soc Clin Oncol 1997; 16: 266aGoogle Scholar
  85. 85.
    Ducreux M, Ychou M, Seitz JF, et al. Irinotecan combined with bolus fluorouracil, continuous-infusion fluorouracil, and high-dose leucovorin every 2 weeks (LV 5-FU2 regimen): a clinical dose-finding study and pharmacokinetic study in patients with previously treated metastatic colorectal cancer. J Clin Oncol 1999; 17: 2901–8PubMedGoogle Scholar
  86. 86.
    Andre T, Louvet C, Maindrault-Goebel F, et al. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion fluorouracil (Folfiri) for pretreated colorectal cancer (GERCOR). Eur J Cancer 1999; 35: 1343–7PubMedGoogle Scholar
  87. 87.
    Saltz LB, Locker PK, Pirotta N, et al. Weekly irinotecan (CPT-11). leucovorin (LV) and fiuorouracil (5-FU) is superior to daily x 5 LV/FU in patients (pts) with previously untreated raetastatic colorectal cancer (CRC) [abstract 898]. Proc Am Soc Clin Oncol 1999; 18: 233aGoogle Scholar
  88. 88.
    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 multicenter randomised trial. Lancet 2000; 355: 1041–7PubMedGoogle Scholar
  89. 89.
    Saltz LB, Cox JV, Blanke C, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 2000; 343: 905–14PubMedGoogle Scholar
  90. 90.
    Nicholls CJ, Cassidy J, Freemantle N, et al. Cost-effectiveness of combination chemotherapy (oxaliplatin or irinotecan in combination with 5-FU/FA) compared to 5-FU/FA alone. J Med Econ 2001; 4: 115–25Google Scholar
  91. 91.
    Levy Piedbois C, Durand-Zaleski I, Juhel H, et al. Cost-effectiveness of second-line treatment with irinotecan or infusional 5-fluorouracil in metastatic colorectal cancer. Ann Oncol 2000; 11: 157–61PubMedGoogle Scholar
  92. 92.
    Trippoli S, Vaiani M, Cattel F, et al. Cost-effectiveness of irinotecan in advanced colorectal cancer. Ann Oncol 2000; 11: 899–900PubMedGoogle Scholar
  93. 93.
    Cunningham D, Falk S, Jackson DL. Irinotecan and infusional 5-fluorouracil as first-line treatment of metastatic colorectal cancer: improved survival and cost-effective compared with infusional 5-FU. Proc Am Soc Clin Oncol 2000; 19: 981Google Scholar
  94. 94.
    Nicholls CJ, Cassidy J, Freemantle N, et al. Cost-effectiveness of oxaliplatin in combination with 5-FU/FA compared with 5-FU/FA alone. J Med Econ 2001; 4: 127–35Google Scholar
  95. 95.
    Vaiani M, Trippoli S, Messori A, et al. Irinotecan plus fiuorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 2001; 344: 305–7PubMedGoogle Scholar
  96. 96.
    Cunningham D, Falk S, Jackson D. Clinical and economic benefits of irinotecan in combination with 5-fluorouracil and folinic acid as first line treatment of metastatic colorectal cancer. Br J Cancer 2002; 86: 1677–83PubMedGoogle Scholar
  97. 97.
    Cvitkovic E, Bekradda M. Oxaliplatin: a new therapeutic option in colorectal cancer. Seroin Oncol 1999; 26(6): 647–662Google Scholar
  98. 98.
    Rixe O, Ortuzar W, Parker M, et al. Oxaliplatin tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute Anti-Cancer Drag Screen Panel. Biochem Pharmacol 1996; 12: 1855–65Google Scholar
  99. 99.
    Gillies-Amar V, Garcia ML, Sebille A, et al. Evolution of severe sensory neuropathy with oxaliplatin, combined to the bimonthly 48h leucovorin (LV) and 5-fluor ouracil (5-FU) regimens (FOLFOX) in metastatic colorectal cancer [abstract 944]. Proc Am Soc Clin Oncol 1999; 18: 246aGoogle Scholar
  100. 100.
    Andre T, Bensmaine MA, Louvet C, et al. Multicenter phase II study of bimonthly high-dose leucovorin, fluorouracil infusion, and oxalipiatin for metastatic colorectal cancer resistant to the same leucovorin and fluorouracil regimen. J Clin Oncol 1999; 17(11): 3560–8PubMedGoogle Scholar
  101. 101.
    Levi F, Zidani R, Misset JL. Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in raetastatic colorectal cancer. Lancet 1997; 350(9079): 681–6PubMedGoogle Scholar
  102. 102.
    Levi FA, Zidani R, Vannetzel JM, et al. Chronornodulated versus fixed-infusionrate delivery of ambulatory chemotherapy by oxaliplatin, fluorouracil and folinic acid (leucovorin) in patients with colorectal metastases: a randomised muitiinstitutional trial. J Nati Cancer Inst 1994; 86(21): 1608–17Google Scholar
  103. 103.
    Giacchetti S, Perpoint B, Zidani R, et al. Phase III randomised trial of oxalipiatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 2000; 18: 136–46PubMedGoogle Scholar
  104. 104.
    de Gramont A, Figer A, Seymour M, et al. Leucovorin and flourouracil, with or without, oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000; 18(16): 2938–47PubMedGoogle Scholar
  105. 105.
    Goldberg RM, Morton RF, Sargent DJ, et al. N9741: oxaliplatin (oxal) or CPT-11 + 5-fluorouracil (5-FU)/leucovorin (LV) or oxal + CPT-11 in advanced colorectal cancer (CRC): initial toxicity and response data from a GI Intergroup study [abstract 511]. Proc Am Soc Clin Oncol 2002; 21: 128aGoogle Scholar
  106. 106.
    Scheele J. Hepatectomy for liver metastases. Br J Surg 1993; 80: 274–6PubMedGoogle Scholar
  107. 107.
    Giacchetti S, Itzhaki M, Gruia G, et al. Long-term survival of patients with unresectable colorectal cancer liver metastases following infusional 5-fluorouracil, leucovorin, oxalipiatin and surgery. Ann Oncol 1999; 10: 663–9PubMedGoogle Scholar
  108. 108.
    Lister-Sharp D, McDonagh M, Saeed Khan K, et al. A systematic review of the effectiveness and cost-effectiveness of the taxanes used in the treatment of advanced breast and ovarian cancer. York: NHS Centre for Reviews and Dissemination, 2000Google Scholar
  109. 109.
    Tournigand C, Achille E, Lledo G, et al. FQLFIRI followed by FOLFOX or FOLFOX followed by FOLFIRI in raetastatic colorectal cancer (MCRC): preliminary results of a randomised phase III study of the GERCOR [abstract]. Ann Oncol 2000; 11Suppl. 4: 43Google Scholar
  110. 110.
    Poston G, Benjamin IS, Diamond T, et al. Costs of neoadjuvant chemotherapy and surgery in patients with liver metastases from advanced colorectal cancer. J Med Econ 2001; 4: 167–77Google Scholar

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© Adis Data Information BV 2003

Authors and Affiliations

  1. 1.Cancer Research UK Department of Medical OncologyUniversity of Glasgow and Beatson Oncology CentreGlasgowUK
  2. 2.Department of Medical OncologyCancer Research UK Beatson LaboratoriesBearsden, GlasgowUK

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