MedKoo product information:

  CPX-1

Description of CPX-1: CPX-1 is a liposomal formulation of Irinotecan HCl: Floxuridine in a synergistic 1:1 molar ratio.  Irinotecan and floxuridine is a drug regimen that has proven activity in the treatment of cancer, particularly against GI tumors. Both drugs are approved for the treatment of colorectal cancer. CPX-1 is currently in a Phase 2 clinical trial as a potential treatment for patients with colorectal cancer. Colorectal cancer represents the first of numerous tumor types where CPX-1 may provide a benefit to patients. Based on these promising clinical results, CPX-1 was advanced into a Phase 2 study in patients with colorectal cancer. (source: http://www.celatorpharma.com/new/products_CPX1.html). 

Current developer:    Celator Pharmaceuticals.

 1: House MG, Kemeny NE, Gönen M, Fong Y, Allen PJ, Paty PB, Dematteo RP, Blumgart LH, Jarnagin WR, D'Angelica MI. Comparison of Adjuvant Systemic Chemotherapy With or Without Hepatic Arterial Infusional Chemotherapy After Hepatic Resection for Metastatic Colorectal Cancer. Ann Surg. 2011 Oct 4. [Epub ahead of print] PubMed PMID: 21975318.

2: Gmeiner WH, Reinhold WC, Pommier Y. Genome-wide mRNA and microRNA profiling of the NCI 60 cell-line screen and comparison of FdUMP[10] with fluorouracil, floxuridine, and topoisomerase 1 poisons. Mol Cancer Ther. 2010 Dec;9(12):3105-14. PubMed PMID: 21159603; PubMed Central PMCID: PMC3059097.

3: Dicko A, Mayer LD, Tardi PG. Use of nanoscale delivery systems to maintain synergistic drug ratios in vivo. Expert Opin Drug Deliv. 2010 Dec;7(12):1329-41. Review. PubMed PMID: 21118030.

4: Chen Y, Yan Z, Wang J, Wang X, Luo J, Liu Q. Hepatic arterial infusion with oxaliplatin, irinotecan and doxifluridine for unresectable liver metastases of colorectal cancer. Anticancer Res. 2010 Jul;30(7):3045-9. PubMed PMID: 20683053.

5: Takanashi K, Minami S, Miyajima N, Hirako T, Hirakawa M, Koh Y, Saitoh T, Ueno Y, Sasagawa Y. [A long term survivor of advanced gastric cancer treated with multi-drug combination chemotherapy]. Gan To Kagaku Ryoho. 2009 Nov;36(12):2278-80. Japanese. PubMed PMID: 20037395.

6: Hazama S, Nagashima A, Kondo H, Yoshida S, Shimizu R, Araki A, Yoshino S, Okayama N, Hinoda Y, Oka M. Phase I study of irinotecan and doxifluridine for metastatic colorectal cancer focusing on the UGT1A1*28 polymorphism. Cancer Sci. 2010 Mar;101(3):722-7. Epub 2009 Nov 7. PubMed PMID: 20028383.

7: Kemeny NE, Melendez FD, Capanu M, Paty PB, Fong Y, Schwartz LH, Jarnagin WR, Patel D, D'Angelica M. Conversion to resectability using hepatic artery infusion plus systemic chemotherapy for the treatment of unresectable liver metastases from colorectal carcinoma. J Clin Oncol. 2009 Jul 20;27(21):3465-71. Epub 2009 May 26. PubMed PMID: 19470932.

8: Batist G, Gelmon KA, Chi KN, Miller WH Jr, Chia SK, Mayer LD, Swenson CE, Janoff AS, Louie AC. Safety, pharmacokinetics, and efficacy of CPX-1 liposome injection in patients with advanced solid tumors. Clin Cancer Res. 2009 Jan 15;15(2):692-700. PubMed PMID: 19147776.

9: Khan AZ, Morris-Stiff G, Makuuchi M. Patterns of chemotherapy-induced hepatic injury and their implications for patients undergoing liver resection for colorectal liver metastases. J Hepatobiliary Pancreat Surg. 2009;16(2):137-44. Epub 2008 Dec 18. Review. PubMed PMID: 19093069.

10: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Sep;30(7):543-88. PubMed PMID: 18985183.

11: Power DG, Healey-Bird BR, Kemeny NE. Regional chemotherapy for liver-limited metastatic colorectal cancer. Clin Colorectal Cancer. 2008 Jul;7(4):247-59. Review. PubMed PMID: 18650193.

12: Martínez C J, Jarufe C N, González D R, Alvarez Z M. [Current therapeutic options for liver metastasis]. Rev Med Chil. 2008 Mar;136(3):376-84. Epub 2008 Jun 3. Review. Spanish. PubMed PMID: 18575666.

13: White RR, Schwartz LH, Munoz JA, Raggio G, Jarnagin WR, Fong Y, D'Angelica MI, Kemeny NE. Assessing the optimal duration of chemotherapy in patients with colorectal liver metastases. J Surg Oncol. 2008 Jun 1;97(7):601-4. PubMed PMID: 18449915.

14: Dicko A, Frazier AA, Liboiron BD, Hinderliter A, Ellena JF, Xie X, Cho C, Weber T, Tardi PG, Cabral-Lilly D, Cafiso DS, Mayer LD. Intra and inter-molecular interactions dictate the aggregation state of irinotecan co-encapsulated with floxuridine inside liposomes. Pharm Res. 2008 Jul;25(7):1702-13. Epub 2008 Mar 5. PubMed PMID: 18320294.

15: Lassmann S, Tang L, Capanu M, Brabletz T, Schöpflin A, Zur Hausen A, Gonen M, Kemeny N, Shia J, Klimstra D, Werner M. Predictive molecular markers for colorectal cancer patients with resected liver metastasis and adjuvant chemotherapy. Gastroenterology. 2007 Dec;133(6):1831-9. Epub 2007 Sep 5. PubMed PMID: 18054556.

16: Gallagher DJ, Capanu M, Raggio G, Kemeny N. Hepatic arterial infusion plus systemic irinotecan in patients with unresectable hepatic metastases from colorectal cancer previously treated with systemic oxaliplatin: a retrospective analysis. Ann Oncol. 2007 Dec;18(12):1995-9. Epub 2007 Oct 24. PubMed PMID: 17962209.

17: Harasym TO, Tardi PG, Harasym NL, Harvie P, Johnstone SA, Mayer LD. Increased preclinical efficacy of irinotecan and floxuridine coencapsulated inside liposomes is associated with tumor delivery of synergistic drug ratios. Oncol Res. 2007;16(8):361-74. PubMed PMID: 17913044.

18: Ishizu K, Sunose N, Yamazaki K, Tsuruo T, Sadahiro S, Makuuchi H, Yamori T. Development and characterization of a model of liver metastasis using human colon cancer HCT-116 cells. Biol Pharm Bull. 2007 Sep;30(9):1779-83. PubMed PMID: 17827739.

19: Ogata Y, Sasatomi T, Mori S, Matono K, Ishibashi N, Akagi Y, Fukushima T, Murakami H, Ushijima M, Shirouzu K. Significance of thymidine phosphorylase in metronomic chemotherapy using CPT-11 and doxifluridine for advanced colorectal carcinoma. Anticancer Res. 2007 Jul-Aug;27(4C):2605-11. PubMed PMID: 17695422.

20: Ardalan B, Kozyreva O, Tsai KT, Santos E, Franceschi D, Livingstone A, Lima M. A phase II study of irinotecan, high-dose 24-h continuous intravenous infusion of floxuridine and leucovorin (IFLUX) for advanced, previously untreated colorectal cancer. Anticancer Drugs. 2007 Sep;18(8):955-61. PubMed PMID: 17667602.

21: Kato T, Mishima H, Ikenaga M, Murata K, Ishida H, Fukunaga M, Ota H, Tominaga S, Ohnishi T, Amano M, Ikeda K, Ikeda M, Sekimoto M, Sakamoto J, Monden M. A phase II study of irinotecan in combination with doxifluridine, an intermediate form of capecitabine, in patients with metastatic colorectal cancer. Cancer Chemother Pharmacol. 2008 Feb;61(2):275-81. Epub 2007 Apr 11. PubMed PMID: 17429630.

22: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2006 Dec;28(10):719-40. PubMed PMID: 17235418.

23: Pasetto LM, Merenda R, Pilati P, Sinigaglia G, Monfardini S. Hepatic metastases of colorectal cancer: locoregional intra-arterial treatment. Anticancer Res. 2006 Nov-Dec;26(6C):4785-92. Review. PubMed PMID: 17214342.

24: Nozawa K, Oomi T, Nakamura K, Aoyagi Y, Hayama T, Yamada H, Haku K, Matsuda K, Mimura T, Watanabe T. [A treatment for pulmonary metastases from colorectal cancer by pre-operative CPT-11/5'-DFUR combination therapy]. Gan To Kagaku Ryoho. 2006 Nov;33(12):1962-4. Japanese. PubMed PMID: 17212160.

25: Tardi PG, Gallagher RC, Johnstone S, Harasym N, Webb M, Bally MB, Mayer LD. Coencapsulation of irinotecan and floxuridine into low cholesterol-containing liposomes that coordinate drug release in vivo. Biochim Biophys Acta. 2007 Mar;1768(3):678-87. Epub 2006 Dec 6. PubMed PMID: 17208196.

26: Inoue Y, Miki C, Watanabe H, Hiro J, Toiyama Y, Ojima E, Nakatani K, Nobori T, Kusunoki M. Irinotecan cytotoxicity does not necessarily depend on the UGT1A1 polymorphism but on fluoropyrimidine: a molecular case report. Oncol Rep. 2006 Nov;16(5):971-4. PubMed PMID: 17016579.

27: Gotoh J, Akabane H, Kita K, Fujiyoshi M, Hirokata G, Imai K, Kawai T, Yanagida N, Nakano S, Takahashi M. [A case of local recurrence of rectal cancer in long-term responding to combined therapy of low-dose CPT-11 and 5'-DFUR]. Gan To Kagaku Ryoho. 2006 Sep;33(9):1349-51. Japanese. PubMed PMID: 16969040.

28: Mayer LD, Harasym TO, Tardi PG, Harasym NL, Shew CR, Johnstone SA, Ramsay EC, Bally MB, Janoff AS. Ratiometric dosing of anticancer drug combinations: controlling drug ratios after systemic administration regulates therapeutic activity in tumor-bearing mice. Mol Cancer Ther. 2006 Jul;5(7):1854-63. PubMed PMID: 16891472.

29: Kuwakado S, Takiuchi H, Goto M, Kawabe S, Ohta S, Kii T, Tanaka T, Nishitani H, Katsu K. [A case of gastric cancer with multiple liver metastases resistant to TS-1 responding to chemotherapy with paclitaxel plus doxifluridine]. Gan To Kagaku Ryoho. 2006 Apr;33(4):513-5. Japanese. PubMed PMID: 16612164.

30: Newman E, Potmesil M, Ryan T, Marcus S, Hiotis S, Yee H, Norwood B, Wendell M, Muggia F, Hochster H. Neoadjuvant chemotherapy, surgery, and adjuvant intraperitoneal chemotherapy in patients with locally advanced gastric or gastroesophageal junction carcinoma: a phase II study. Semin Oncol. 2005 Dec;32(6 Suppl 9):S97-100. PubMed PMID: 16399443.

31: Tanaka K, Noura S, Ohue M, Takachi K, Kishi K, Eguchi H, Yamada T, Miyashiro I, Yano M, Ohigashi H, Sasaki Y, Ishikawa O, Imaoka S, Kameyama M, Murata K. [A case of chemoradiation with tissue expander for local reccurence of rectal cancer]. Gan To Kagaku Ryoho. 2005 Oct;32(11):1779-81. Japanese. PubMed PMID: 16315939.

32: Tsujie M, Fujiwara S, Kida H, Hayashi N, Fukuchi S, Yoshida T, Ebisui C, Sakita I, Hasuike Y, Fujimoto T. [A case of metastatic colon cancer treated with oxaliplatin combination chemotherapy]. Gan To Kagaku Ryoho. 2005 Oct;32(11):1774-5. Japanese. PubMed PMID: 16315937.

33: Urien S, Rezaí K, Lokiec F. Pharmacokinetic modelling of 5-FU production from capecitabine--a population study in 40 adult patients with metastatic cancer. J Pharmacokinet Pharmacodyn. 2005 Dec;32(5-6):817-33. PubMed PMID: 16284918.

34: Sawada T, Nishimura M, Hirose K. [Long-term survival in a case of large bowel cancer--efficacy of CPT-11-based chemotherapy]. Gan To Kagaku Ryoho. 2005 Jul;32(7):1059-61. Japanese. PubMed PMID: 16044974.

35: Kemeny N, Jarnagin W, Paty P, Gönen M, Schwartz L, Morse M, Leonard G, D'Angelica M, DeMatteo R, Blumgart L, Fong Y. Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. J Clin Oncol. 2005 Aug 1;23(22):4888-96. Epub 2005 Jul 11. PubMed PMID: 16009951.

36: Fiorentini G, Rossi S, Bernardeschi P, Cantore M, Guadagni S. Is there a new drug beyond floxuridine for intra-arterial hepatic chemotherapy in liver metastases from colorectal cancer? J Clin Oncol. 2005 Mar 20;23(9):2105; author reply 2106. PubMed PMID: 15774801.

37: Mishima H, Kato T, Yanagisawa M, Tsujinaka T, Nishisho I, Tsujie M, Fujimoto-Ouchi K, Tanaka Y, Kikkawa N. Sequential treatment with irinotecan and doxifluridine: optimal dosing schedule in murine models and in a phase I study for metastatic colorectal cancer. Chemotherapy. 2005 Mar;51(1):32-9. Epub 2005 Mar 14. PubMed PMID: 15767743.

38: Tamesa T, Watanabe Y, Yoshimura K, Mori N, Yamamoto S, Hazama S, Tangoku A, Oka M. [A case of disseminated tumor from cecal cancer with survival for over 5 years after twice surgical resection and systemic chemotherapy]. Gan To Kagaku Ryoho. 2004 Oct;31(11):1864-6. Japanese. PubMed PMID: 15553741.

39: Inoue Y, Shirane M, Miki C, Hiro J, Tanaka K, Kobayashi M, Mori K, Yanagi H, Kusunoki M. Gene expression profiles of colorectal carcinoma in response to neo-adjuvant chemotherapy. Int J Oncol. 2004 Dec;25(6):1641-9. PubMed PMID: 15547701.

40: Meyers M, Hwang A, Wagner MW, Boothman DA. Role of DNA mismatch repair in apoptotic responses to therapeutic agents. Environ Mol Mutagen. 2004;44(4):249-64. Review. PubMed PMID: 15468331.

41: Patel M, Agarwal R, Ardalan B. Effects of oxaliplatin and CPT-11 on cytotoxicity and nucleic acid incorporation of the fluoropyrimidines. J Cancer Res Clin Oncol. 2004 Aug;130(8):453-9. Epub 2004 Jun 15. PubMed PMID: 15205948.

42: Haraguchi Y, Shimizu H, Takahashi M, Nakano M, Okusawa A, Suzuki M. [Two cases of metastatic or recurrent rectal cancer responding to combined chemotherapy of low-dose CPT-11 and 5'-DFUR as second-line chemotherapy]. Gan To Kagaku Ryoho. 2004 Mar;31(3):419-22. Japanese. PubMed PMID: 15045953.

43: Kato T, Kikkawa N, Tsujie M, Iijima S, Handa R, Naoi Y, Oshima S, Yamamoto H, Kurokawa E. [A case of hepatic metastasis and local recurrence from rectal cancer responding to hepatic arterial infusion and systemic chemotherapy]. Gan To Kagaku Ryoho. 2003 Oct;30(11):1729-32. Japanese. PubMed PMID: 14619505.

44: Gill S, Thomas RR, Goldberg RM. Review article: colorectal cancer chemotherapy. Aliment Pharmacol Ther. 2003 Oct 1;18(7):683-92. Review. PubMed PMID: 14510741.

45: Kemeny N, Jarnagin W, Gonen M, Stockman J, Blumgart L, Sperber D, Hummer A, Fong Y. Phase I/II study of hepatic arterial therapy with floxuridine and dexamethasone in combination with intravenous irinotecan as adjuvant treatment after resection of hepatic metastases from colorectal cancer. J Clin Oncol. 2003 Sep 1;21(17):3303-9. PubMed PMID: 12947066.

46: Lin T, Zhang L, Davis J, Gu J, Nishizaki M, Ji L, Roth JA, Xiong M, Fang B. Combination of TRAIL gene therapy and chemotherapy enhances antitumor and antimetastasis effects in chemosensitive and chemoresistant breast cancers. Mol Ther. 2003 Sep;8(3):441-8. PubMed PMID: 12946317.

47: Yanagisawa M, Ishikawa T, Ouchi KF, Tanaka Y. [Optimal dosing schedule in combination therapy with irinotecan and doxifluridine in a human colorectal cancer xenograft model]. Gan To Kagaku Ryoho. 2003 Feb;30(2):223-30. Japanese. PubMed PMID: 12610870.

48: Bonetti A. Hepatic artery infusion for liver metastases from colorectal cancer. Lancet. 2003 Feb 1;361(9355):358-9. PubMed PMID: 12573366.

49: Sato A, Shimada K, Nakamachi M, Ushio J, Yamamoto W, Kurihara M, Matsukawa M. Effectiveness of doxifluridine (5'-DFUR)/docetaxel against advanced/recurrent gastric cancer showing resistance to various anticancer drug regimens. Gastric Cancer. 2002;5(4):233-6. PubMed PMID: 12491082.

50: Bilchik AJ, Wood TF, Chawla SP, Rose DM, Chung MH, Stern SS, Foshag LJ, Ramming KP. Systemic irinotecan or regional floxuridine chemotherapy prolongs survival after hepatic cryosurgery in patients with metastatic colon cancer refractory to 5-fluorouracil. Clin Colorectal Cancer. 2001 May;1(1):36-42. PubMed PMID: 12445377.

51: Ojima E, Miki C, Hatada T, Inoue Y, Mohri T, Azuma T, Kusunoki M. [A case of colon metastasis to the lung treated successfully with combined chemotherapy of CPT-11 and 5'-DFUR]. Gan To Kagaku Ryoho. 2002 Oct;29(10):1845-8. Japanese. PubMed PMID: 12402441.

52: Newman E, Marcus SG, Potmesil M, Sewak S, Yee H, Sorich J, Hayek M, Muggia F, Hochster H. Neoadjuvant chemotherapy with CPT-11 and cisplatin downstages locally advanced gastric cancer. J Gastrointest Surg. 2002 Mar-Apr;6(2):212-23; discussion 223. PubMed PMID: 11992807.

53: Litvak DA, Wood TF, Tsioulias GJ, Chung M, Chawla SP, Foshag LJ, Morton DL, Ramming KP, Bilchik AJ. Systemic irinotecan and regional floxuridine after hepatic cytoreduction in 185 patients with unresectable colorectal cancer metastases. Ann Surg Oncol. 2002 Mar;9(2):148-55. PubMed PMID: 11888871.

54: Wagman LD. Fighting wars, winning battles. Ann Surg Oncol. 2002 Mar;9(2):115-6. PubMed PMID: 11888865.

55: Ogata Y, Sasatomi T, Araki Y, Ishibashi N, Nozoe Y, Miyagi Y, Nakagawa M, Matono K, Kishimoto Y, Hayashi A, Mituoka M, Konishi J, Shirouzu K. [A case of lung metastasis from colon cancer treated successfully with combined chemotherapy of CPT-11 and 5'-DFUR]. Gan To Kagaku Ryoho. 2001 Nov;28(12):1917-21. Japanese. PubMed PMID: 11729488.

56: Kemeny N, Gonen M, Sullivan D, Schwartz L, Benedetti F, Saltz L, Stockman J, Fong Y, Jarnagin W, Bertino J, Tong W, Paty P. Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer. J Clin Oncol. 2001 May 15;19(10):2687-95. PubMed PMID: 11352961.

57: Sasaki K, Takasaka H, Kawasaki H, Oono K, Nakayama I, Matsunaga T, Takaoka A, Aoki S, Hamamatsu C, Hirayama T, Nakagawa N, Shibata K, Yabana T, Yamamoto Y, Hirata K. [Weekly low dose CPT-11 for multiple lung metastases of colon cancer on an out-patient treatment: a case report]. Nihon Shokakibyo Gakkai Zasshi. 2001 Feb;98(2):157-61. Japanese. PubMed PMID: 11235190.

58: Conroy T, Paillot B, Adenis A. [New drugs in gastrointestinal oncology. Current status and future directions]. Gastroenterol Clin Biol. 1999 Nov;23(11):1145-65. Review. French. PubMed PMID: 10651534.

59: Ferguson PJ, Collins O, Dean NM, DeMoor J, Li CS, Vincent MD, Koropatnick J. Antisense down-regulation of thymidylate synthase to suppress growth and enhance cytotoxicity of 5-FUdR, 5-FU and Tomudex in HeLa cells. Br J Pharmacol. 1999 Aug;127(8):1777-86. PubMed PMID: 10482907; PubMed Central PMCID: PMC1566173.

60: Matsumoto S, Mashiba H, Okamoto K, Ekimoto H. [Evaluation of antitumor activity of etoposide administered orally for 21 consecutive days against human uterine cancer subcutaneous and/or orthotopic xenografts in nude mice]. Gan To Kagaku Ryoho. 1999 Aug;26(9):1313-20. Japanese. PubMed PMID: 10478185.

61: Hartmann JT, Bokemeyer C. Chemotherapy for renal cell carcinoma. Anticancer Res. 1999 Mar-Apr;19(2C):1541-3. Review. PubMed PMID: 10365141.

62: Taguchi T. [Gastrointestinal cancer and oral anticancer agents]. Gan To Kagaku Ryoho. 1999 Feb;26(3):284-94. Review. Japanese. PubMed PMID: 10065090.

63: Goldberg RM. Is repeated treatment with a 5-fluorouracil-based regimen useful in colorectal cancer? Semin Oncol. 1998 Oct;25(5 Suppl 11):21-8. Review. PubMed PMID: 9786313.

64: Bertino JR. Chemotherapy of colorectal cancer: history and new themes. Semin Oncol. 1997 Oct;24(5 Suppl 18):S18-3-S18-7. Review. PubMed PMID: 9420015.

65: Isacoff WH, Borud K. Chemotherapy for the treatment of patients with metastatic colorectal cancer: an overview. World J Surg. 1997 Sep;21(7):748-62. Review. PubMed PMID: 9276707.

66: Patt YZ, Hoque A, Lozano R, Pozdur R, Chase J, Carrasco H, Chuang V, Delpassand ES, Ellis L, Curley S, Roh M, Jones DV Jr. Phase II trial of hepatic arterial infusion of fluorouracil and recombinant human interferon alfa-2b for liver metastases of colorectal cancer refractory to systemic fluorouracil and leucovorin. J Clin Oncol. 1997 Apr;15(4):1432-8. PubMed PMID: 9193336.

67: Geoffroy F, Grem JL. Chemotherapy of advanced gastrointestinal cancer. Curr Opin Oncol. 1994 Jul;6(4):427-34. Review. PubMed PMID: 7803544.