Display options
Cite
Löhr JM, Haas SL, Kröger JC, et al. Encapsulated cells expressing a chemotherapeutic activating enzyme allow the targeting of subtoxic chemotherapy and are safe and efficacious: data from two clinical trials in pancreatic cancer. Pharmaceutics. 2014;6(3):447-66doi: 10.3390/pharmaceutics6030447.
Löhr, J. M., Haas, S. L., Kröger, J. C., Friess, H. M., Höft, R., Goretzki, P. E., Peschel, C., Schweigert, M., Salmons, B., & Gunzburg, W. H. (2014). Encapsulated cells expressing a chemotherapeutic activating enzyme allow the targeting of subtoxic chemotherapy and are safe and efficacious: data from two clinical trials in pancreatic cancer. Pharmaceutics, 6(3), 447-66. https://doi.org/10.3390/pharmaceutics6030447
Löhr, J Matthias, et al. "Encapsulated cells expressing a chemotherapeutic activating enzyme allow the targeting of subtoxic chemotherapy and are safe and efficacious: data from two clinical trials in pancreatic cancer." Pharmaceutics vol. 6,3 (2014): 447-66. doi: https://doi.org/10.3390/pharmaceutics6030447
Löhr JM, Haas SL, Kröger JC, Friess HM, Höft R, Goretzki PE, Peschel C, Schweigert M, Salmons B, Gunzburg WH. Encapsulated cells expressing a chemotherapeutic activating enzyme allow the targeting of subtoxic chemotherapy and are safe and efficacious: data from two clinical trials in pancreatic cancer. Pharmaceutics. 2014 Aug 11;6(3):447-66. doi: 10.3390/pharmaceutics6030447. PMID: 25116885; PMCID: PMC4190529.
Copy Download .nbib Format: NLM
Share it on

Pharmaceutics. 2014 Aug 11;6(3):447-66. doi: 10.3390/pharmaceutics6030447.

Encapsulated cells expressing a chemotherapeutic activating enzyme allow the targeting of subtoxic chemotherapy and are safe and efficacious: data from two clinical trials in pancreatic cancer.

Pharmaceutics

J Matthias Löhr, Stephan L Haas, Jens C Kröger, Helmut M Friess, Raimund Höft, Peter E Goretzki, Christian Peschel, Markus Schweigert, Brian Salmons, Walter H Gunzburg

Affiliations

  1. Gastrocentrum, Karolinska University Hospital, Hälsovägen 1, SE-141 86 Stockholm, Sweden. [email protected].
  2. Gastrocentrum, Karolinska University Hospital, Hälsovägen 1, SE-141 86 Stockholm, Sweden. [email protected].
  3. Institute of Diagnostic und Interventional Radiology, University Medicine Rostock, Ernst-Heydemann-Strasse 6, D-18057 Rostock, Germany. [email protected].
  4. Department of Surgery, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, D-81675 Munich, Germany. [email protected].
  5. Abteilung für Gastroenterologie, Klinik und Poliklinik für Innere Medizin, Universität Rostock, Ernst-Heydemann-Strasse 6, D-18057 Rostock, Germany. [email protected].
  6. Chirurgische Klinik und Poliklinik, Medizinische Einrichtungen der Heinrich Heine Universität, Moorenstrasse 5, D-40225 Düsseldorf, Germany. [email protected].
  7. Medizinische Klinik und Poliklinik, Klinikum Rechts der Isar der Technischen Universität München III, Ismaninger Strasse 22, D-81675 Munich, Germany. [email protected].
  8. Medizinische Klinik (Onkologie/Hämatologie) Campus Mitte, Universitätsklinikum Charité II, Schumannstrasse 21/22, D-10098 Berlin, Germany. [email protected].
  9. Austrianova Singapore Pte Ltd, Centros, Biopolis, Singapore. [email protected].
  10. Austrianova Singapore Pte Ltd, Centros, Biopolis, Singapore. [email protected].

PMID: 25116885 PMCID: PMC4190529 DOI: 10.3390/pharmaceutics6030447

Abstract

Despite progress in the treatment of pancreatic cancer, there is still a need for improved therapies. In this manuscript, we report clinical experience with a new therapy for the treatment of pancreatic cancer involving the implantation of encapsulated cells over-expressing a cytochrome P450 enzyme followed by subsequent low-dose ifosfamide administrations as a means to target activated ifosfamide to the tumor. The safety and efficacy of the angiographic instillation of encapsulated allogeneic cells overexpressing cytochrome P450 in combination with low-dose systemic ifosfamide administration has now been evaluated in 27 patients in total. These patients were successfully treated in four centers by three different interventional radiologists, arguing strongly that the treatment can be successfully used in different centers. The safety of the intra-arterial delivery of the capsules and the lack of evidence that the patients developed an inflammatory or immune response to the encapsulated cells or encapsulation material was shown in all 27 patients. The ifosfamide dose of 1 g/m2/day used in the first trial was well tolerated by all patients. In contrast, the ifosfamide dose of 2 g/m2/day used in the second trial was poorly tolerated in most patients. Since the median survival in the first trial was 40 weeks and only 33 weeks in the second trial, this strongly suggests that there is no survival benefit to increasing the dose of ifosfamide, and indeed, a lower dose is beneficial for quality of life and the lack of side effects. This is supported by the one-year survival rate in the first trial being 38%, whilst that in the second trial was only 23%. However, taking the data from both trials together, a total of nine of the 27 patients were alive after one year, and two of these nine patients were alive for two years or more.

References

  1. Eur J Cancer. 1993;29A(2):290 - PubMed
  2. J Cancer Res Clin Oncol. 1991;117 Suppl 4:S135-8 - PubMed
  3. Oncology. 2003;65 Suppl 2:7-10 - PubMed
  4. N Engl J Med. 2011 May 12;364(19):1817-25 - PubMed
  5. Drug Metab Dispos. 1997 Aug;25(8):985-93 - PubMed
  6. Cancer Chemother Pharmacol. 1986;18 Suppl 2:S55-6 - PubMed
  7. J Cancer Res Clin Oncol. 1995;121(5):297-302 - PubMed
  8. Anticancer Drugs. 2008 Mar;19(3):295-302 - PubMed
  9. Lancet. 2011 Aug 13;378(9791):607-20 - PubMed
  10. Adv Exp Med Biol. 1998;451:97-106 - PubMed
  11. Gene Ther. 1998 Aug;5(8):1070-8 - PubMed
  12. Nature. 2010 Oct 28;467(7319):1109-13 - PubMed
  13. Crit Rev Oncol Hematol. 2012 Apr;82(1):40-50 - PubMed
  14. Cancer Gene Ther. 2001 Mar;8(3):220-30 - PubMed
  15. Cancer Res. 1995 Feb 1;55(3):581-9 - PubMed
  16. Chemotherapy. 2011;57(2):156-61 - PubMed
  17. Methods. 2013 Jun 1;61(2):117-29 - PubMed
  18. J Clin Oncol. 2007 Jun 20;25(18):2607-15 - PubMed
  19. J Clin Oncol. 1988 Nov;6(11):1703-7 - PubMed
  20. Adv Exp Med Biol. 2010;670:92-103 - PubMed
  21. Front Oncol. 2012 Jan 31;2:6 - PubMed
  22. Ann N Y Acad Sci. 1999 Jun 18;875:46-63 - PubMed
  23. PLoS One. 2013 Oct 23;8(10):e78130 - PubMed
  24. Pancreas. 1995 Jul;11(1):77-85 - PubMed
  25. Cancer Treat Rep. 1981 Mar-Apr;65(3-4):357-8 - PubMed
  26. Cancer Res. 1996 Mar 15;56(6):1331-40 - PubMed
  27. PLoS One. 2014 Jul 16;9(7):e102061 - PubMed
  28. Lancet. 2001 May 19;357(9268):1591-2 - PubMed
  29. Cancer Chemother Pharmacol. 1993;33(1):36-42 - PubMed
  30. Expert Opin Investig Drugs. 2002 Jun;11(6):769-86 - PubMed
  31. J Clin Oncol. 1985 Mar;3(3):367-72 - PubMed
  32. Ann N Y Acad Sci. 1999 Jun 30;880:326-36 - PubMed
  33. Handb Clin Neurol. 2012;105:903-16 - PubMed
  34. Ann N Y Acad Sci. 1999 Jun 30;880:337-51 - PubMed
  35. Chem Res Toxicol. 1996 Mar;9(2):351-60 - PubMed
  36. Curr Opin Mol Ther. 2010 Aug;12(4):450-60 - PubMed
  37. Ann Oncol. 2006 May;17 Suppl 4:iv33-6 - PubMed
  38. World J Gastroenterol. 2014 Mar 7;20(9):2247-54 - PubMed
  39. Adv Biol Regul. 2014 Sep;56:45-50 - PubMed
  40. Expert Rev Clin Immunol. 2014 Jan;10(1):19-30 - PubMed
  41. J Pharmacol Exp Ther. 2009 Feb;328(2):598-609 - PubMed
  42. Cancer Immun. 2013;13:2 - PubMed
  43. J Mol Med (Berl). 1999 Apr;77(4):393-8 - PubMed
  44. Cancers (Basel). 2011 Jan 18;3(1):368-95 - PubMed
  45. Int J Oncol. 2014 Jun;44(6):2132-8 - PubMed
  46. Pancreatology. 2003;3(1):55-63 - PubMed
  47. J Gastroenterol. 2003 Mar;38 Suppl 15:78-84 - PubMed
  48. Nature. 2010 Oct 28;467(7319):1114-7 - PubMed
  49. N Engl J Med. 2013 Oct 31;369(18):1691-703 - PubMed
  50. J Mol Med (Berl). 2002 Sep;80(9):610-4 - PubMed
  51. Nat Rev Cancer. 2013 Jan;13(1):66-74 - PubMed

Publication Types