Combination Intraperitoneal Chemotherapy Is Superior to Mitomycin C or Oxaliplatin for Colorectal Carcinomatosis In Vivo
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Hyperthermic intraperitoneal (IP) chemotherapy after cytoreduction improves survival in patients with colorectal carcinomatosis of the peritoneal surface. Most protocols use single agents (mitomycin C or oxaliplatin) provided IP. The purpose of this study was to determine whether combination IP chemotherapy is superior to single-agent therapy in a mouse model.
Nu/Nu mice were injected IP with HT-29 colorectal cancer cells. Animals were treated with single agents or combinations. Primary end point was overall survival. Agents explored included oxaliplatin, mitomycin C, panitumumab, erlotinib, cetuximab, and irinotecan delivered IP as single agents; mitomycin C, panitumumab, and irinotecan in combination IP; and 5-fluorouracil–leucovorin–irinotecan (FOLFIRI) in combination delivered intravenously.
Survival of mice receiving irinotecan or mitomycin C IP was greater than controls. Median survival of mice receiving intravenous FOLFIRI was also greater than control. However, survival of mice receiving IP irinotecan or mitomycin C was far greater than mice receiving intravenous FOLFIRI. For combination therapy, a positive interaction was observed with mitomycin C and irinotecan, whereas survival was greater than either agent individually. No interaction was observed between panitumumab and mitomycin C or irinotecan. However, an overall survival benefit was observed with the combination of irinotecan, mitomycin C, and panitumumab; at 120 days after cell injection, 100% of the triagent therapy group survived.
IP therapy with mitomycin C or irinotecan provided a survival benefit compared with intravenous FOLFIRI. Combination IP therapy with mitomycin C, panitumumab, and irinotecan was superior to all other agents tested alone or in combination. This warrants further combination analysis and supports consideration for a phase I application.
- Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96. CrossRef
- Levin B, Brooks D, Smith RA, Stone A. Emerging technologies in screening for colorectal cancer: CT colonography, immunochemical fecal occult blood tests, and stool screening using molecular markers. CA Cancer J Clin. 2003;53:44–55. CrossRef
- Esquivel J, Elias D, Baratti D, et al. Consensus statement on the loco regional treatment of colorectal cancer with peritoneal dissemination. J Surg Oncol. 2008;98:263–7. CrossRef
- Hurwitz HI, Fehrenbacher L, Hainsworth JD, et al. Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol. 2005;23:3502–8. CrossRef
- Chu DZ, Lang NP, Thompson C, et al. Peritoneal carcinomatosis in nongynecologic malignancy. A prospective study of prognostic factors. Cancer. 1989;63:364–7. CrossRef
- Jayne DG, Fook S, Loi C, Seow-Choen F. Peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2002;89:1545–50. CrossRef
- Sadeghi B, Arvieux C, Glehen O, et al. Peritoneal Carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 Multicentric Prospective Study. Cancer. 2000;88:358–63. CrossRef
- Cunliffe WJ, Sugarbaker PH. Gastrointestinal malignancy: rationale for adjuvant therapy using early postoperative intraperitoneal chemotherapy. Br J Surg. 1989;76:1082–90. CrossRef
- Akaishi E, Teixeira F, Katayama M, et al. Peritonectomy for peritoneal carcinomatosis: long-term outcomes from a single Brazilian institution. World J Surg. 2009;33:835–9. CrossRef
- Ceelen WP, Peeters M, Houtmeyers P, et al. Safety and efficacy of hyperthermic intraperitoneal chemoperfusion with high-dose oxaliplatin in patients with peritoneal carcinomatosis. Ann Surg Oncol. 2008;15:535–41. CrossRef
- Glehen O, Kwiatkowski F, Sugarbaker PH, 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;22:3284–92. CrossRef
- van Leeuwen BL, Graf W, Pahlman L, Mahteme H. Swedish experience with peritonectomy and HIPEC. HIPEC in peritoneal carcinomatosis. Ann Surg Oncol. 2008;15:745–53. CrossRef
- Verwaal VJ, Bruin S, Boot H, et al. 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;15:2426–32. CrossRef
- Yang XJ, Li Y, Al-shammaa Hassan AH, et al. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival in selected patients with peritoneal carcinomatosis from abdominal and pelvic malignancies: results of 21 cases. Ann Surg Oncol. 2009;16:345–51. CrossRef
- Cavaliere F, Valle M, De Simone M, et al. 120 peritoneal carcinomatoses from colorectal cancer treated with peritonectomy and intra-abdominal chemohyperthermia: a SITILO multicentric study. In Vivo. 2006;20:747–50.
- Yan TD, Welch L, Black D, Sugarbaker PH. A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma. Ann Oncol. 2007;18:827–34. CrossRef
- Elias D, Raynard B, Farkhondeh F, et al. Peritoneal carcinomatosis of colorectal origin. Gastroenterol Clin Biol. 2006;30:1200–4.
- Kusamura S, Dominique E, Baratti D, et al. Drugs, carrier solutions and temperature in hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2008;98:247–52. CrossRef
- Sugarbaker PH. Building on a consensus. J Surg Oncol. 2008;98(4):215–6. CrossRef
- Elias D, Matsuhisa T, Sideris L, et al. Heated intra-operative intraperitoneal oxaliplatin plus irinotecan after complete resection of peritoneal carcinomatosis: pharmacokinetics, tissue distribution and tolerance. Ann Oncol. 2004;15:1558–65. CrossRef
- Green SK, Karlsson MC, Ravetch JV, Kerbel RS. Disruption of cell-cell adhesion enhances antibody-dependent cellular cytotoxicity: implications for antibody-based therapeutics of cancer. Cancer Res. 2002;62:6891–900.
- Pearson JW, FitzGerald DJ, Willingham MC, et al. Chemoimmunotoxin therapy against a human colon tumor (HT-29) xenografted into nude mice. Cancer Res. 1989;49:3562–7.
- Wildner O, Morris JC. Therapy of peritoneal carcinomatosis from colon cancer with oncolytic adenoviruses. J Gene Med. 2000;2:353–60. CrossRef
- Birle DC, Hedley DW. Signaling interactions of rapamycin combined with erlotinib in cervical carcinoma xenografts. Mol Cancer Ther. 2006;5:2494–502. CrossRef
- Cusack JCJ, Liu R, Xia L, et al. NPI-0052 enhances tumoricidal response to conventional cancer therapy in a colon cancer model. Clin Cancer Res. 2006;12:6758–64. CrossRef
- Foon KA, Yang XD, Weiner LM, et al. Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys. 2004;58:984–90.
- Kimura M, Konno T, Miyamoto Y, et al. Intracavitary administration: pharmacokinetic advantages of macromolecular anticancer agents against peritoneal and pleural carcinomatoses. Anticancer Res. 1998;18:2547–50.
- Ruan HH, Scott KR, Bautista E, Ammons WS. ING-1(heMAb), a monoclonal antibody to epithelial cell adhesion molecule, inhibits tumor metastases in a murine cancer model. Neoplasia. 2003;5:489–94.
- Roby KF, Taylor CC, Sweetwood JP, et al. Development of a syngeniec mouse model for events related to ovarian cancer. Carcinogenesis. 2000;21:585–91. CrossRef
- 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;343:905–14. CrossRef
- Caponigro F, Milano A, Ottaiano A, Iaffaioli RV. Epidermal growth factor receptor as a major anticancer drug target. Expert Opin Ther Targets. 2006;10:877–88. CrossRef
- Johnston JB, Navaratnam S, Pitz MW, et al. Targeting the EGFR pathway for cancer therapy. Curr Med Chem. 2006;13:3483–92. CrossRef
- Nautiyal J, Rishi AK, Majumdar AP. Emerging therapies in gastrointestinal cancers. World J Gastroenterol. 2006;12:7440–50.
- Scaltriti M, Baselga J. The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res. 2006;12:5268–72. CrossRef
- 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;26:1626–34. CrossRef
- Jhawer M, Goel S, Wilson A, et al. PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab. Cancer Res. 2008;68:1953–61. CrossRef
- de Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18:2938–47.
- Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med. 2005;352:476–87. CrossRef
- Elias D, Lefevre JH, Chevalier J, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27:681–5. CrossRef
- Balin-Gauthier D, Delord JP, Rochaix P, et al. In vivo and in vitro antitumor activity of oxaliplatin in combination with cetuximab in human colorectal tumor cell lines expressing different level of EGFR. Cancer Chemother Pharmacol. 2006;57:709–18. CrossRef
- Bauer TW, Fan F, Liu W, et al. Targeting of insulin-like growth factor-I receptor with a monoclonal antibody inhibits growth of hepatic metastases from human colon carcinoma in mice. Ann Surg Oncol. 2007;14:2838–46. CrossRef
- Leonetti C, Scarsella M, Zupi G, et al. Efficacy of a nitric oxide-releasing nonsteroidal anti-inflammatory drug and cytotoxic drugs in human colon cancer cell lines in vitro and xenografts. Mol Cancer Ther. 2006;5:919–26. CrossRef
- Moser C, Lang SA, Kainz S, et al. Blocking heat shock protein-90 inhibits the invasive properties and hepatic growth of human colon cancer cells and improves the efficacy of oxaliplatin in p53-deficient colon cancer tumors in vivo. Mol Cancer Ther. 2007;6:2868–78. CrossRef
- Tabernero J, Van Cutsem E, Díaz-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;25:5225–32. CrossRef
- Vasilevskaya IA, Selvakumaran M, O’Dwyer P. Disruption of signaling through SEK1 and MKK7 yields differential responses in hypoxic colon cancer cells treated with oxaliplatin. Mol Pharmacol. 2008;74:246–54. CrossRef
- Yao Y, Zhao H, Sun Y, et al. Combined chemotherapy of hydroxycampothecin with oxaliplatin as an adjuvant treatment for human colorectal cancer. Tohoku J Exp Med. 2008;215:267–78. CrossRef
- Hribaschek A, Pross M, Kuhn R, et al. Prevention and treatment of peritoneal carcinomatosis in experimental investigations with CPT-11 and oxaliplatin. Anticancer Drugs. 2002;13:605–14. CrossRef
- Yokoo S, Masuda S, Yonezawa A, et al. Significance of organic cation transporter 3 (SLC22A3) expression for the cytotoxic effect of oxaliplatin in colorectal cancer. Drug Metab Dispos. 2008;36:2299–306. CrossRef
- Huang ZH, Hua D, Du X, et al. ERCC1 polymorphism, expression and clinical outcome of oxaliplatin-based adjuvant chemotherapy in gastric cancer. World J Gastroenterol. 2008;14:6401–7. CrossRef
- Kim SH, Kwon HC, Oh SY, et al. Prognostic value of ERCC1, thymidylate synthase, and glutathione S-transferase pi for 5-FU/oxaliplatin chemotherapy in advanced colorectal cancer. Am J Clin Oncol. 2009;32:38–43. CrossRef
- Fichtner I, Slisow W, Gill J, et al. Anticancer drug response and expression of molecular markers in early-passage xenotransplanted colon carcinomas. Eur J Cancer. 2004;40:298–307. CrossRef
- Mohamed F, Marchettini P, Stuart OA, et al. Thermal enhancement of new chemotherapeutic agents at moderate hyperthermia. Ann Surg Oncol. 2003;10:463–8. CrossRef
- Pestieau SR, Belliveau JF, Griffin H, et al. Pharmacokinetics of intraperitoneal oxaliplatin: experimental studies. J Surg Oncol. 2001;76:106–14. CrossRef
- Aarts F, Hendriks T, Boerman OC, et al. A comparison between radioimmunotherapy and hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis of colonic origin in rats. Ann Surg Oncol. 2007;14:3274–82. CrossRef
- Pelz JO, Doerfer J, Hohenberger W, Meyer T. A new survival model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing rats in the treatment of peritoneal carcinomatosis. BMC Cancer. 2005;5:56. CrossRef
- Le Page S, Kwiatkowski F, Paulin C, et al. In vitro thermochemotherapy of colon cancer cell lines with irinotecan alone and combined with mitomycin C. Hepatogastroenterology. 2006;53:693–7.
- Van der Speeten K, Stuart OA, Sugarbaker PH. Using pharmacologic data to plan clinical treatments for patients with peritoneal surface malignancy. Curr Drug Discov Technol. 2009;6:72–81. CrossRef
- Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34–43. CrossRef
- Giuliani F, Molica S, Maiello E, et al. Irinotecan (CPT-11) and mitomycin-C (MMC) as second-line therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico dell’ Italia Meridionale (prot. 2106). Am J Clin Oncol. 2005;28:581–5. CrossRef
- Nishino K, Aoki Y, Amikura T, et al. Irinotecan hydrochloride (CPT-11) and mitomycin C as the first line chemotherapy for ovarian clear cell adenocarcinoma. Gynecol Oncol. 2005;97:893–7. CrossRef
- Yamada Y, Shirao K, Hyodo I, et al. Phase II study of biweekly irinotecan and mitomycin C combination therapy in patients with fluoropyrimidine-resistant advanced colorectal cancer. Cancer Chemother Pharmacol. 2003;52:125–30. CrossRef
- Kuzuya T, Yamauchi M, Ito A, et al. Pharmacokinetic characteristics of 5-fluorouracil and mitomycin C in intraperitoneal chemotherapy. J Pharm Pharmacol. 1994;46:685–9.
- Sugarbaker PH, Graves T, DeBruijn EA, et al. Early postoperative intraperitoneal chemotherapy as an adjuvant therapy to surgery for peritoneal carcinomatosis from gastrointestinal cancer: pharmacological studies. Cancer Res. 1990;50:5790–4.
- Sugarbaker PH, Stuart OA, Vidal-Jove J, et al. Pharmacokinetics of the peritoneal-plasma barrier after systemic mitomycin C administration. Cancer Treat Res. 1996;82:41.
- Elias D, Raynard B, Bonnay M, Pocard M. Heated intra-operative intraperitoneal oxaliplatin alone and in combination with intraperitoneal irinotecan: pharmacologic studies. Eur J Surg Oncol. 2006;32:607–13. CrossRef
- Hribaschek A, Kuhn R, Pross M, et al. Intraperitoneal versus intravenous CPT-11 given intra- and postoperatively for peritoneal carcinomatosis in a rat model. Surg Today. 2006;36:57–62. CrossRef
- Gobert C, Bracco L, Rossi F, et al. Modulation of DNA topoisomerase I activity by p53. Biochemistry. 1996;35:5778–86. CrossRef
- Villalona-Calero MA, Kolesar JM. Mitomycin as a modulator of irinotecan anticancer activity. Oncology. 2002;16:21–5.
- Xu Y, Shapiro CL. Rationale for mitomycin and irinotecan use in advanced breast cancer. Oncology. 2003;17:25–8.
- Combination Intraperitoneal Chemotherapy Is Superior to Mitomycin C or Oxaliplatin for Colorectal Carcinomatosis In Vivo
Annals of Surgical Oncology
Volume 17, Issue 1 , pp 296-303
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- 1. Department of Surgery, University of Kansas Medical Center, Kansas City, KS, USA
- 2. Department of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
- 3. Pharmacy Practice, University of Kansas Medical Center, Kansas City, KS, USA
- 4. Office of Therapeutics Discovery and Development, University of Kansas Medical Center, Kansas City, KS, USA
- 5. Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Blvd. MS 3050, Kansas City, KS, USA