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
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...
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| Language: | English |
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MDPI AG
2014-08-01
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| Series: | Pharmaceutics |
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| Online Access: | http://www.mdpi.com/1999-4923/6/3/447 |
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| author | 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 |
| author_facet | 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 |
| author_sort | J. Matthias Löhr |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T13:40:31Z |
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| id | doaj.art-434329c2a44c4e2799229a8dc22d2f9b |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T13:40:31Z |
| publishDate | 2014-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-434329c2a44c4e2799229a8dc22d2f9b2022-12-22T04:21:16ZengMDPI AGPharmaceutics1999-49232014-08-016344746610.3390/pharmaceutics6030447pharmaceutics6030447Encapsulated Cells Expressing a Chemotherapeutic Activating Enzyme Allow the Targeting of Subtoxic Chemotherapy and Are Safe and Efficacious: Data from Two Clinical Trials in Pancreatic CancerJ. Matthias Löhr0Stephan L. Haas1Jens C. Kröger2Helmut M. Friess3Raimund Höft4Peter E. Goretzki5Christian Peschel6Markus Schweigert7Brian Salmons8Walter H. Gunzburg9Gastrocentrum, Karolinska University Hospital, Hälsovägen 1, SE-141 86 Stockholm, SwedenGastrocentrum, Karolinska University Hospital, Hälsovägen 1, SE-141 86 Stockholm, SwedenInstitute of Diagnostic und Interventional Radiology, University Medicine Rostock, Ernst-Heydemann-Strasse 6, D-18057 Rostock, GermanyDepartment of Surgery, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, D-81675 Munich, GermanyAbteilung für Gastroenterologie, Klinik und Poliklinik für Innere Medizin, Universität Rostock, Ernst-Heydemann-Strasse 6, D-18057 Rostock, GermanyChirurgische Klinik und Poliklinik, Medizinische Einrichtungen der Heinrich Heine Universität, Moorenstrasse 5, D-40225 Düsseldorf, GermanyMedizinische Klinik und Poliklinik, Klinikum Rechts der Isar der Technischen Universität München III, Ismaninger Strasse 22, D-81675 Munich, GermanyMedizinische Klinik (Onkologie/Hämatologie) Campus Mitte, Universitätsklinikum Charité II, Schumannstrasse 21/22, D-10098 Berlin, GermanyAustrianova Singapore Pte Ltd, Centros, Biopolis, SingaporeAustrianova Singapore Pte Ltd, Centros, Biopolis, SingaporeDespite 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.http://www.mdpi.com/1999-4923/6/3/447pancreatic cancercytochrome P450cell therapyencapsulationifosfamidesafetyefficacybioencapsulationtargeting chemotherapylow dosequality of life |
| spellingShingle | 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 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 pancreatic cancer cytochrome P450 cell therapy encapsulation ifosfamide safety efficacy bioencapsulation targeting chemotherapy low dose quality of life |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | pancreatic cancer cytochrome P450 cell therapy encapsulation ifosfamide safety efficacy bioencapsulation targeting chemotherapy low dose quality of life |
| url | http://www.mdpi.com/1999-4923/6/3/447 |
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