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Role of Chemotherapy in Peritoneal Carcinomatosis in Metastatic Colorectal Cancer

  • Therapeutic Approaches to Metastatic Colorectal Cancers (E Díaz-Rubio, Section Editor)
  • Published:
Current Colorectal Cancer Reports

Abstract

Peritoneal carcinomatosis from colorectal cancer is increasingly recognized as a special form of metastatic disease. This review focuses on the efficacy of systemic chemotherapy in the setting of peritoneal carcinomatosis. Peritoneal carcinomatosis-affected individuals succumb to their disease earlier than those without known carcinomatosis, with an approximately 30 % reduction in overall survival. Modern cytotoxic combination chemotherapy incorporating oxaliplatin and irinotecan has resulted in marked improvement of overall survival among carcinomatosis patients, but not to the same extent as for non-carcinomatosis patients. Biologicals are also associated with increased overall survival, but still seem to underperform in the carcinomatosis patient. Efficacy of 5FU monotherapy seems negligible. Evidence suggests future trials should be stratified by peritoneal carcinomatosis status. Complementary benefits of systemic chemotherapy and cytoreductive surgical approaches warrant further studies.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013;132(5):1133–45. doi:10.1002/ijc.27711.

    Article  PubMed  CAS  Google Scholar 

  2. Varghese S, Burness M, Xu H, Beresnev T, Pingpank J, Alexander HR. Site-specific gene expression profiles and novel molecular prognostic factors in patients with lower gastrointestinal adenocarcinoma diffusely metastatic to liver or peritoneum. Ann Surg Oncol. 2007;14(12):3460–71. doi:10.1245/s10434-007-9557-7.

    Article  PubMed  Google Scholar 

  3. Levine EA, Blazer 3rd DG, Kim MK, Shen P, Stewart JH, Guy C, et al. Gene expression profiling of peritoneal metastases from appendiceal and colon cancer demonstrates unique biologic signatures and predicts patient outcomes. J Am Coll Surg. 2012;214(4):599–606. doi:10.1016/j.jamcollsurg.2011.12.028. discussion −7.

    Article  PubMed  Google Scholar 

  4. Blair SL, Chu DZ, Schwarz RE. Outcome of palliative operations for malignant bowel obstruction in patients with peritoneal carcinomatosis from nongynecological cancer. Ann Surg Oncol. 2001;8(8):632–7.

    Article  PubMed  CAS  Google Scholar 

  5. Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J, et al. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer. 2000;88(2):358–63. doi:10.1002/(SICI)1097-0142(20000115)88:2<358::AID-CNCR16>3.0.CO;2-O.

    Article  PubMed  CAS  Google Scholar 

  6. Sugarbaker PH, Jablonski KA. Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy. Ann Surg. 1995;221(2):124–32.

    Article  PubMed  CAS  Google Scholar 

  7. •• Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21(20):3737–43. doi:10.1200/JCO.2003.04.187. First and only completed randomized trail focusing on patients with isolated peritoneal carcinomatosis—comparing best systemic chemotherapy available at that time (5FU, minority patients also irinotecan) with or without cytoreductive surgery plus intraperitoneal chemotherapy. Patients randomized to systemic chemotherapy plus cytoreduction survived longer on intention-to-treat analysis (HR = 0.55).

    Article  PubMed  Google Scholar 

  8. Elias D, Lefevre JH, Chevalier J, Brouquet A, Marchal F, Classe JM, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27(5):681–5. doi:10.1200/JCO.2008.19.7160.

    Article  PubMed  Google Scholar 

  9. Franko J, Ibrahim Z, Gusani NJ, Holtzman MP, Bartlett DL, Zeh 3rd HJ. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. Cancer. 2010;116(16):3756–62. doi:10.1002/cncr.25116.

    Article  PubMed  Google Scholar 

  10. •• Franko J, Shi Q, Goldman CD, Pockaj BA, Nelson GD, Goldberg RM, et al. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol. 2012;30(3):263–7. doi:10.1200/JCO.2011.37.1039. Largest available secondary analysis of systemic chemotherapy trials with attention to peritoneal carcinomatosis. Patients with peritoneal carcinomatosis benefited from systemic chemotherapy, but survived shorter (HR = 1.4).

    Article  PubMed  Google Scholar 

  11. Pelz JO, Chua TC, Esquivel J, Stojadinovic A, Doerfer J, Morris DL, et al. Evaluation of best supportive care and systemic chemotherapy as treatment stratified according to the retrospective peritoneal surface disease severity score (PSDSS) for peritoneal carcinomatosis of colorectal origin. BMC Cancer. 2010;10:689. doi:10.1186/1471-2407-10-689.

    Article  PubMed  CAS  Google Scholar 

  12. Pelz JO, Stojadinovic A, Nissan A, Hohenberger W, Esquivel J. Evaluation of a peritoneal surface disease severity score in patients with colon cancer with peritoneal carcinomatosis. J Surg Oncol. 2009;99(1):9–15. doi:10.1002/jso.21169.

    Article  PubMed  Google Scholar 

  13. Khattak MA, Martin HL, Beeke C, Price T, Carruthers S, Kim S, et al. Survival differences in patients with metastatic colorectal cancer and with single site metastatic disease at initial presentation: results from South Australian clinical registry for advanced colorectal cancer. Clin Colorectal Cancer. 2012;11(4):247–54. doi:10.1016/j.clcc.2012.06.004.

    Article  PubMed  Google Scholar 

  14. Assersohn L, Norman A, Cunningham D, Benepal T, Ross PJ, Oates J. Influence of metastatic site as an additional predictor for response and outcome in advanced colorectal carcinoma. Br J Cancer. 1999;79(11–12):1800–5. doi:10.1038/sj.bjc.6690287.

    PubMed  CAS  Google Scholar 

  15. •• Klaver YL, Simkens LH, Lemmens VE, Koopman M, Teerenstra S, Bleichrodt RP, et al. Outcomes of colorectal cancer patients with peritoneal carcinomatosis treated with chemotherapy with and without targeted therapy. Eur J Surg Oncol. 2012;38(7):617–23. doi:10.1016/j.ejso.2012.03.008. European secondary analysis of systemic chemotherapy trials with attention to peritoneal carcinomatosis. Patients with peritoneal carcinomatosis benefited from systemic chemotherapy, but survived shorter. Outcomes were comparable with those in North American study in Ref. [10].

    Article  PubMed  CAS  Google Scholar 

  16. • Segelman J, Granath F, Holm T, Machado M, Mahteme H, Martling A. Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2012;99(5):699–705. doi:10.1002/bjs.8679. Detailed analysis of peritoneal carcinomatosis incidence and development after diagnosis of any stage CRC in population.

    Article  PubMed  CAS  Google Scholar 

  17. Jayne DG, Fook S, Loi C, Seow-Choen F. Peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2002;89(12):1545–50. doi:10.1046/j.1365-2168.2002.02274.x.

    Article  PubMed  CAS  Google Scholar 

  18. Kerscher AG, Chua TC, Gasser M, Maeder U, Kunzmann V, Isbert C, Germer CT, Pelz JO. Impact of peritoneal carcinomatosis in the disease history of colorectal cancer management: a longitudinal experience of 2406 patients over two decades. Br J Cancer. 2013;108(7):1432–9. doi:10.1038/bjc.2013.82.

    Google Scholar 

  19. • Lemmens VE, Klaver YL, Verwaal VJ, Rutten HJ, Coebergh JW, de Hingh IH. Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study. Int J Cancer. 2011;128(11):2717–25. doi:10.1002/ijc.25596. Detailed analysis of peritoneal carcinomatosis outcomes in defined population and changes over time. Peritoneal carcinomatosis was associated with poorer outcome.

    Article  PubMed  CAS  Google Scholar 

  20. Stewart JH, Shen P, Levine EA. Intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy: current status and future directions. Ann Surg Oncol. 2005;12(10):765–77.

    Google Scholar 

  21. Yokota T, Ura T, Shibata N, Takahari D, Shitara K, Nomura M, et al. BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer. Br J Cancer. 2011;104(5):856–62. doi:10.1038/bjc.2011.19.

    Article  PubMed  CAS  Google Scholar 

  22. Helyer LK, Law CH, Butler M, Last LD, Smith AJ, Wright FC. Surgery as a bridge to palliative chemotherapy in patients with malignant bowel obstruction from colorectal cancer. Ann Surg Oncol. 2007;14(4):1264–71. doi:10.1245/s10434-006-9303-6.

    Article  PubMed  Google Scholar 

  23. Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.

    Article  PubMed  CAS  Google Scholar 

  24. Gilly FN, Carry PY, Sayag AC, Brachet A, Panteix G, Salle B, et al. Regional chemotherapy (with mitomycin C) and intra-operative hyperthermia for digestive cancers with peritoneal carcinomatosis. Hepatogastroenterology. 1994;41(2):124–9.

    PubMed  CAS  Google Scholar 

  25. Klaver YL, Lemmens VE, Creemers GJ, Rutten HJ, Nienhuijs SW, de Hingh IH. Population-based survival of patients with peritoneal carcinomatosis from colorectal origin in the era of increasing use of palliative chemotherapy. Ann Oncol. 2011;22(10):2250–6. doi:10.1093/annonc/mdq762.

    Article  PubMed  CAS  Google Scholar 

  26. • Köhne CH, Cunningham D, Di Costanzo F, Glimelius B, Blijham G, Aranda E, et al. Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients. Ann Oncol. 2002;13(2):308–17. Detailed analysis of efficacy of 5FU chemotherapy in mCRC demonstrating significant outcome variability. Information on peritoneal carcinomatosis was missing among 30 % cases, but peritoneal carcinomatosis was associated with poorer outcome.

    Article  PubMed  Google Scholar 

  27. Folprecht G, Köhne C-H, Lutz M. Systemic chemotherapy in patients with peritoneal carcinomatosis from colorectal cancer. In: Ceelen WP, editor. Peritoneal carcinomatosis: a multidisciplinary approach. Cancer treatment and research, vol 134: Springer, New York; 2007. p. 425–40.

  28. Zani S, Papalezova K, Stinnett S, Tyler D, Hsu D, Blazer 3rd DG. Modest advances in survival for patients with colorectal-associated peritoneal carcinomatosis in the era of modern chemotherapy. J Surg Oncol. 2012. doi:10.1002/jso.23222.

    PubMed  Google Scholar 

  29. Lee DH, Oh SY, Lee YR, Huh SJ, Yoon HH, Kim SH, et al. A phase II study of modified FOLFOX4 for colorectal cancer patients with peritoneal carcinomatosis. Cancer Res Treat. 2011;43(4):225–30. doi:10.4143/crt.2011.43.4.225.

    Article  PubMed  Google Scholar 

  30. Grothey A, Sargent D. Overall survival of patients with advanced colorectal cancer correlates with availability of fluorouracil, irinotecan, and oxaliplatin regardless of whether doublet or single-agent therapy is used first line. J Clin Oncol. 2005;23(36):9441–2. doi:10.1200/JCO.2005.04.479.

    Article  PubMed  Google Scholar 

  31. Tournigand C, Andre 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(2):229–37. doi:10.1200/JCO.2004.05.113.

    Article  PubMed  CAS  Google Scholar 

  32. Chua TC, Morris DL, Saxena A, Esquivel J, Liauw W, Doerfer J, et al. Influence of modern systemic therapies as adjunct to cytoreduction and perioperative intraperitoneal chemotherapy for patients with colorectal peritoneal carcinomatosis: a multicenter study. Ann Surg Oncol. 2011;18(6):1560–7. doi:10.1245/s10434-010-1522-1.

    Article  PubMed  Google Scholar 

  33. Chu DZ, Lang NP, Thompson C, Osteen PK, Westbrook KC. Peritoneal carcinomatosis in nongynecologic malignancy. A prospective study of prognostic factors. Cancer. 1989;63(2):364–7.

    Article  PubMed  CAS  Google Scholar 

  34. Köhne C-H, Bokemeyer C, Folprecht G, Sartorius U, Schlichting M, Rougier PR et al. Cetuximab plus chemotherapy in patients with liver-limited or non-liver-limited KRAS wild-type colorectal metastases: a pooled analysis of the CRYSTAL and OPUS studies. J Clin Oncol. 2012;30(suppl 4):abstr 96.

  35. Yan TD, Black D, Sugarbaker PH, Zhu J, Yonemura Y, Petrou G, et al. A systematic review and meta-analysis of the randomized controlled trials on adjuvant intraperitoneal chemotherapy for resectable gastric cancer. Ann Surg Oncol. 2007;14(10):2702–13. doi:10.1245/s10434-007-9487-4.

    Article  PubMed  Google Scholar 

  36. Fajardo AD, Tan B, Reddy R, Fleshman J. Delayed repeated intraperitoneal chemotherapy after cytoreductive surgery for colorectal and appendiceal carcinomatosis. Dis Colon Rectum. 2012;55(10):1044–52. doi:10.1097/DCR.0b013e318265ad42.

    Article  PubMed  Google Scholar 

  37. Glehen O, Kwiatkowski F, Sugarbaker PH, Elias D, Levine EA, De Simone M, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22(16):3284–92. doi:10.1200/JCO.2004.10.012.

    Article  PubMed  CAS  Google Scholar 

  38. Vaillant JC, Nordlinger B, Deuffic S, Arnaud JP, Pelissier E, Favre JP, et al. Adjuvant intraperitoneal 5-fluorouracil in high-risk colon cancer: a multicenter phase III trial. Ann Surg. 2000;231(4):449–56.

    Article  PubMed  CAS  Google Scholar 

  39. Nordlinger B, Rougier P, Arnaud JP, Debois M, Wils J, Ollier JC, et al. Adjuvant regional chemotherapy and systemic chemotherapy versus systemic chemotherapy alone in patients with stage II-III colorectal cancer: a multicentre randomised controlled phase III trial. Lancet Oncol. 2005;6(7):459–68. doi:10.1016/S1470-2045(05)70222-9.

    Article  PubMed  CAS  Google Scholar 

  40. Ceelen WP, Bracke ME. Peritoneal minimal residual disease in colorectal cancer: mechanisms, prevention, and treatment. Lancet Oncol. 2009;10(1):72–9. doi:10.1016/S1470-2045(08)70335-8.

    Article  PubMed  Google Scholar 

  41. Pelz JO, Doerfer J, Dimmler A, Hohenberger W, Meyer T. Histological response of peritoneal carcinomatosis after hyperthermic intraperitoneal chemoperfusion (HIPEC) in experimental investigations. BMC Cancer. 2006;6:162. doi:10.1186/1471-2407-6-162.

    Article  PubMed  Google Scholar 

  42. Shen P, Hawksworth J, Lovato J, Loggie BW, Geisinger KR, Fleming RA, et al. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy with mitomycin C for peritoneal carcinomatosis from nonappendiceal colorectal carcinoma. Ann Surg Oncol. 2004;11(2):178–86.

    Article  PubMed  Google Scholar 

  43. Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H. 8-year follow-up of randomized trial: cytoreduction and hyperthermic Intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol. 2008;15(9):2426–32. doi:10.1245/s10434-008-9966-2.

    Article  PubMed  Google Scholar 

  44. Sugarbaker PH, Mora JT, Carmignani P, Stuart OA, Yoo D. Update on chemotherapeutic agents utilized for perioperative intraperitoneal chemotherapy. Oncologist. 2005;10(2):112–22. doi:10.1634/theoncologist.10-2-112.

    Article  PubMed  CAS  Google Scholar 

  45. Elias D, Goere D, Blot F, Billard V, Pocard M, Kohneh-Shahri N, et al. Optimization of hyperthermic intraperitoneal chemotherapy with oxaliplatin plus irinotecan at 43 degrees C after compete cytoreductive surgery: mortality and morbidity in 106 consecutive patients. Ann Surg Oncol. 2007;14(6):1818–24. doi:10.1245/s10434-007-9348-1.

    Article  PubMed  Google Scholar 

  46. Heiss MM, Murawa P, Koralewski P, Kutarska E, Kolesnik OO, Ivanchenko VV, et al. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer. 2010;127(9):2209–21. doi:10.1002/ijc.25423.

    Article  PubMed  CAS  Google Scholar 

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Jan Franko declares that he has no conflict of interest.

  Charles D. Goldman declares that he has no conflict of interest.

  Kiran K. Turaga declares that he has no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Department of Surgery, Mercy Medical Center, 411 Laurel St, Ste 2100, Des Moines, IA, 50314, USA

    Jan Franko & Charles D. Goldman

  2. Division of Surgical Oncology, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, WI, 53226, USA

    Kiran K. Turaga

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  1. Jan Franko
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Correspondence to Jan Franko.

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Franko, J., Goldman, C.D. & Turaga, K.K. Role of Chemotherapy in Peritoneal Carcinomatosis in Metastatic Colorectal Cancer. Curr Colorectal Cancer Rep 9, 242–249 (2013). https://doi.org/10.1007/s11888-013-0173-6

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