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
نویسندگان
چکیده
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.
منابع مشابه
Wild Type p53 Gene Transfer Increases Chemosensitivity and Apoptotic Response of PANC-1 Pancreatic Tumor Cell Line
The effect of p53 gene therapy on chemosensitivity and apoptotic response of PANC-1 tumor cells, which express high amount of mutant p53, to cancer chemotherapeutic agents of Etoposide and Doxorubicin was investigated. Comparison of the chemosensitivity of PANC-1 cells to its wild type p53 transfectants showed that wt-p53 expressing transfectants are more sensitive to both Etoposide and Doxorub...
متن کاملSystemic Targeted Alpha Radiotherapy for Cancer
Background: The fundamental principles of internal targeted alpha therapy for cancer were established many decades ago.The high linear energy transfer (LET) of alpha radiation to the targeted cancer cellscauses double strand breaks in DNA. At the same time, the short range radiation spares adjacent normal tissues. This targeted approach complements conventional external beam radiotherapy and ch...
متن کاملSubsieve-size agarose capsules enclosing ifosfamide-activating cells: a strategy toward chemotherapeutic targeting to tumors.
Localized activation of the prodrug ifosfamide in or close to tumors by implanting encapsulated ifosfamide-activating cells is an efficacious strategy for tumor therapy. The aim of this study was to evaluate the feasibility of subsieve-size agarose capsules for enclosing the cells in this application. Compared with many conventional microcapsules, subsieve-size agarose capsules are about one-te...
متن کاملTargeting Colorectal Cancer Cell Lines Using Nanobodies; AgSK1as a Potential Target
Background: Colorectal cancer is the third most common type of aggressive cancers. Chemotherapy, surgery,and radiotherapy are the common therapeutic options for treating this cancer. Due to the adverse side-eff ects of these methods, immunotherapy is considered as an appropriate alternative therapeutic option. Treatment through the application of monoclonal antibodies is considered as a n...
متن کاملDopamine-conjugated apoferritin protein nanocage for the dual-targeting delivery of epirubicin
Objective(s): Nanocarriers are drug delivery vehicles, which have attracted the attention of researchers in recent years, particularly in cancer treatment. The encapsulation of anticancer drugs using protein nanocages is considered to be an optimal approach to reducing drug side-effects and increasing the bioavailability of anticancer drugs. Epirubicin (EPR) is an active chemotherapeutic medica...
متن کامل