Seminars in Colon & Rectal Surgery
Volume 19, Issue 4 , Pages 216-225 , December 2008

Therapy for Unresectable Metastatic Colorectal Cancer

  • Jeffrey W. Clark

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Jeffrey Clark, Massachusetts General Hospital, 55 Fruit Street, POB 234, Boston, MA 02114. Phone: 617-643-3415; Fax: 617-724-1136

References 

  1. Goldberg RM, Rothenberg ML, Van Cutsem E, et al. The continuum of care: a paradigm for the management of metastatic colorectal cancer. Oncologist. 2007;12:38–50
  2. Kelly H, Goldberg RM. Systemic therapy for metastatic colorectal cancer: current options, current evidence. J Clin Oncol. 2005;23:4553–4560
  3. Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med. 2005;352:476–487
  4. Koopman M, Antonini NF, Douma J, et al. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet. 2007;370:135–142
  5. Seymour MT, Maughan TS, Ledermann JA, et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet. 2007;370:143–152
  6. 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
  7. Tournigand C, Andre T, Achille E, 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
  8. Falcone A, Ricci S, Brunetti I, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25:1670–1676
  9. Souglakos J, Androulakis N, Syrigos K, et al. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer. 2006;94:798–805
  10. Masi G, Loupakis F, Fornaro L, et al. Outcome of initially unresectable metastatic colorectal cancer (MCRC) patients (pts) treated with first-line FOLFOXIRI followed by R0 surgical resection of metastases (mts) (2008 ASCO Annual Meeting Proceedings Part I). [abstract 4074] J Clin Oncol. 2008;26(15 Suppl):196s
  11. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–2342
  12. Maindrault-Goebel F, Lledo G, Chibaudel B, et al. Final results of OPTIMOX2, a large randomized phase II study of maintenance therapy or chemotherapy-free intervals (CFI) after FOLFOX in patients with metastatic colorectal cancer (MRC) (A GERCOR study). [abstract] J Clin Oncol. 2007;25:166s
  13. Gunnar Folprecht and Claus-Henning Köhne: Drug insight: metastatic colorectal cancer—oral fluoropyrimidines and new perspectives in the adjuvant setting. Nat Clin Pract Oncol. 2005;2:578–587
  14. 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 tissue. Eur J Cancer. 1998;34:1274–1281
  15. Hoff PM, Ansari 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 randomized phase III study. J Clin Oncol. 2001;19:2282–2292
  16. Van Cutsem E, Twelves C, Cassidy J, 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
  17. Porschen R, Arkenau HT, Kubicka S, 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
  18. Cassidy J, Clarke S, Diaz-Rubio E, et al. XELOX vs. FOLFOX4: efficacy results from XELOX-1/N016966, a randomized phase III trial in first-line metastatic colorectal cancer (MCRC). [abstract 237] 2007;Data presented at the 4th annual ASCO Gastrointestinal Cancers Symposium, Orlando, FL, January 20
  19. Hochster HS, Welles L, Hart L, et al. Safety and efficacy of bevacizumab (Bev) when added to oxaliplatin/fluoropyrimidine (O/F) regimens as first-line treatment of metastatic colorectal cancer (mCRC): TREE 1 & 2 Studies. [abstract] J Clin Oncol. 2005;23:254a
  20. Hochster HS, Hart LL, Ramanathan RK, et al. Safety and efficacy of oxaliplatin/fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC): Final analysis of the TREE study. [abstract] J Clin Oncol. 2006;24:148s
  21. Diaz-Rubio E, Tabernero J, Gomez-Espana A, et al. Phase III Study of Capecitabine Plus Oxaliplatin Versus 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
  22. Reinacher-Schick AC, Kubicka S, Freier W, et al. Activity of the combination of bevacizumab (BEV) with capecitabine/irinotecan (CapIRI/Bev) or capecitabine/oxaliplatin (CapOX/Bev) in advanced colorectal cancer (ACRC): a randomized phase II study of the AIO Colorectal Study Group (AIO trial 0604) (2008 ASCO Annual Meeting Proceedings Part I). [abstract 4030] J Clin Oncol. 2008;26(15 Suppl):185s
  23. Fuchs CS, Marshall J, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: updated results from the BICC-C study. J Clin Oncol. 2008;26:689
  24. Jain RK, Duda DK, Clark JW, et al. Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol. 2006;3:24–40
  25. Kerbel RS. Tumor angiogenesis. N Engl J Med. 2008;358:2039–2049
  26. Takahashi Y, Kitadai Y, Bucana CD, et al. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res. 1995;55:3964–3968
  27. Tokunaga T, Oshika Y, Abe Y, et al. Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is correlated with liver metastasis and poor prognosis in colon cancer. Br J Cancer. 1998;77:998–1002
  28. Warren RS, Yuan H, Matli MR, et al. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J Clin Invest. 1995;95:1789–1797
  29. Kabbinavar F, Hurwitz HI, Fehrenbacher L, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol. 2003;21:60–65
  30. Falcone A, Masi G, Loupakis F, et al. FOLFOXIRI (irinotecan, oxaliplatin, and infusional 5FU/LV) in combination with bevacizumab (BV) in the first-line treatment of metastatic colorectal cancer (mCRC): a phase II study by the G.O.N.O. group (2008 ASCO Annual Meeting Proceedings Part I). [abstract 4031] J Clin Oncol. 2008;26(15 Suppl):185s
  31. Grothey A, Hedrick EE, Muss RD, et al. Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF2107. J Clin Oncol. 2008;26:183–189
  32. Willett CG, Boucher Y, di Tomaso E, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 2004;10:145–147
  33. Kozloff MF, Sugrue MM, Purdie DM, et al. Safety and effectiveness of bevacizumab (BV) and chemotherapy (CT) in elderly patients (pts) with metastatic colorectal cancer (mCRC) Results from the BRiTE observational cohort study. [abstract 4026] J Clin Oncol. 2008;26:184s
  34. Italiano A. Targeting the epidermal growth factor receptor in colorectal cancer: advances and controversies. Oncology. 2006;70:161–167
  35. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–345
  36. Jonker DJ, O'Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007;357:2040–2048
  37. Saltz L, Rubin M, Hochster H, et al. Cetuximab (IMC-225) plus irinotecan is active in CPT-11-refractory colorectal cancer that expresses epidermal growth factor receptor. [abstract] Proc Am Soc Clin Oncol. 2001;20:31
  38. Chung KY, Shia J, Kemeny NE, et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol. 2005;23:1803–1810
  39. Lenz HJ, Van Cutsem E, Khambata-Ford S, et al. Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol. 2006;24:4914–4921
  40. Carcereny E, Maurel J. Monoclonal antibodies against epidermal growth factor receptor in advanced colorectal carcinoma: clinical efficacy and markers of sensitivity. Rev Recent Clin Trials. 2006;1:113–118
  41. Lievre A, Bachet JB, Le Corre D, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006;66:3992–3995
  42. Saltz LB, Meropol NJ, Loehrer PJ, et al. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol. 2004;22:1201–1208
  43. Van Cutsem E, Humblet Y, Gelderblom H, et al. Cetuximab dose-escalation study in patients with metastatic colorectal cancer (mCRC) with no or slight skin reactions on cetuximab standard dose treatment (EVEREST): Pharmacokinetic and efficacy data of a randomized study. [abstract 237] Orlando, FL: Gastrointestinal Cancers Symposium; 2007;January 20
  44. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–345
  45. Van Cutsem E, Nowacki M, Lang I, et al. Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer(mCRC): the CRYSTAL trial. [abstract 237] J Clin Oncol. 2007;25:164s
  46. Venook A, Niedzwicki D, Hollis D, et al. Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX)±cetuximab for patients with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preiminary results. [abstract 237] J Clin Oncol. 2006;24:148s
  47. Yokoi K, Thaker PH, Tazici S, et al. Dual inhibition of epidermal growth factor receptor and vascular endothelial growth factor receptor phosphorylation by AEE788 reduces growth and metastasis of human colon carcinoma in an orthotopic nude mouse model. Cancer Res. 2005;65:3716–3725
  48. Saltz LB, Lenz HJ, Hochster H, et al. Randomized phase II trial of cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer. [abstract 3508] Proc Am Soc Clin Oncol. 2005;23:248s
  49. Punt CJ, Tol J, Rodenberg CJ, et al. Randomized phase III study of capecitabine, oxaliplatin, and bevacizumab with or without cetuximab in advanced colorectal cancer (ACC), the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG) (2008 ASCO Annual Meeting Proceedings Part II). [abstract LBA4011] J Clin Oncol. 2008;26(18 Suppl):1008s
  50. Hecht JR, Chidiac T, Mitchell E, et al. An interim analysis of efficacy and safety from a randomized controlled trial of panitumumab with chemotherapy plus bevacizumab for metastatic colorectal cancer. [abstract] 2007;Data presented at the 9th World Conference on Gastrointestinal Cancer, Barcelona, Spain, June 27-30
  51. Tabernero J, Van Cutsem E, Diaz-Rubio E, et al. Phase II trial of cetuximab in combination with fluorouracil, leucovorin, and oxaliplatin in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2007;25:5225–5232
  52. Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007;25:1658–1664
  53. Hecht JR, Patnaik A, Berlin J, Venook A, et al. Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Cancer. 2007;110:980–988
  54. Berlin J, Van Cutsem E, Peeters M, et al. Predictive value of skin toxicity severity for response to panitumumab in patients with metastatic colorectal cancer (mCRC): pooled analysis of five clinical trials. [abstract] J Clin Oncol. 2007;25:196s
  55. Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:1626–1634
  56. Siena S, Tabernero J, Burkes RL, et al. Phase III study (PRIME/20050203) of panitumumab (pmab) with FOLFOX compared with FOLFOX alone in patients (pts) with previously untreated metastatic colorectal cancer (mCRC): Pooled safety data (2008 ASCO Annual Meeting Proceedings Part I). [abstract 4034] J Clin Oncol. 2008;26(15 Suppl):186s
  57. Lee A, Ezzeldin H, Fourie J, et al. Dihydropyrimidine dehydrogenase deficiency: impact of pharmacogenetics on 5-fluorouracil therapy. [review] Clin Adv Hematol Oncol. 2004;2:527–532
  58. Innocenti F, Ratain MJ. Pharmacogenetics of irinotecan: clinical perspectives on the utility of genotyping. Pharmacogenomics. 2006;7:1211–1221
  59. Lievre A, Bachet JB, Boige V, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008;26:374–379
  60. Khambata-Ford S, Garrett CR, Meropol NJ, et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol. 2007;25:3230–3237
  61. Cutsem E Van, Lang I, D'haens G, et al. KRAS status and efficacy in the first-line treatment of patients ith metastatic colrectal cancer (mCRC) treated with FOLFIRI with or without cetuximab (The CRYSTAL experience. 2008 ASCO Annual Meeting Proceedings Part I). [abstract 2] J Clin Oncol. 2008;26(15 Suppl):5s
  62. Pao W, Wang TY, Riely GJ, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2005;2:e17
  63. Wilson PM, Ladner RD, Lenz HJ. Exploring alternative individualized treatment strategies in colorectal cancer. [review] Clin Colorectal Cancer. 2007;7(Suppl 1):S28–S36
  64. Lentz F, Tran A, Rey E, et al. Pharmacogenomics of fluorouracil, irinotecan, and oxaliplatin in hepatic metastases of colorectal cancer: clinical implications. Am J Pharmacogenomics. 2005;5:21–33
  65. Shankara V, Wisinski KB, Mulcahy MF, et al. The role of molecular markers in predicting response to therapy in patients with colorectal cancer. Mol Diagn Ther. 2008;12:87–98
  66. Solonga D, Danenberg KD, Johnson M, et al. Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase, and thymidine phosphorylase. Clin Cancer Res. 2000;6:1322–1327
  67. Lenz HJ. Pharmacogenomics and colorectal cancer. Adv Exp Med Biol. 2006;587:211–231
  68. Graziano F, Ruzzo A, Loupakis F, et al. Pharmacogenetic profiling for cetuximab plus irinotecan therapy in patients with refractory advanced colorectal cancer. J Clin Oncol. 2008;26:1427–1434
  69. Tournigand C, Cervantes A, Figer A, et al. OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer—a GERCOR study. J Clin Oncol. 2006;24:394–400
  70. Maindrault-Goebel F, Lledo G, Chibaudel B, et al. Final results of OPTIMOX2, a large randomized phase II study of maintenance therapy or chemotherapy-free intervals (CFI) after FOLFOX in patients with metastatic colorectal cancer (MRC): a GERCOR study. [abstract 4013] Proc Am Soc Clin Oncol. 2007;25:166s
  71. Labianca R, Floriani I, Cortes E, et al. Alternating versus continuous “FOLFIRI” in advanced colorectal cancer (ACC): a randomized “GISCAD” trial (2006 ASCO Annual Meeting Proceedings Part I). [abstract 3505] J Clin Oncol. 2006;24:3505
  72. Grothey A, Hart LL, Rowland KM, et al. Intermittent oxaliplatin (oxali) administration and time-to-treatment-failure (TTF) in metastatic colorectal cancer (mCRC): Final results of the phase III CONcePT trial (2008 ASCO Annual Meeting Proceedings Part I). [abstract 4010] J Clin Oncol. 2008;26(15 Suppl):180s
  73. Diehl F, Schmidt K, Chot MA, et al. Circulating tumor DNA as a cancer biomarker (2008 ASCO Annual Meeting Proceedings Part I). [abstract 4122] J Clin Oncol. 2008;26(15 Suppl):208s
  74. Timotheadou E, Papakostas P, Tsavdaridis D, et al. Irinotecan and oxaliplatin combination, as second-line treatment, in fluoropyrimidine-pretreated advanced colorectal cancer (A phase II study by the Hellenic Cooperative Oncology Group (HeCOG)). Tumori. 2005;91:309–313
  75. Nikcevich DA, Grothey A, Sloan JA, et al. Effect of intravenous calcium and magnesium (IV CaMg) on oxaliplatin-induced sensory neurotoxicity (sNT) in adjuvant colon cancer: Results of the phase III placebo-controlled, double-blind NCTG trial N04C7 (2008 ASCO Annual Meeting Proceedings Part I). [abstract 4009] J Clin Oncol. 2008;26(15 Suppl):180s

PII: S1043-1489(08)00056-0

doi: 10.1053/j.scrs.2008.09.006

Seminars in Colon & Rectal Surgery
Volume 19, Issue 4 , Pages 216-225 , December 2008

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