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.
Highlights
Even though substantial progress has been made in unraveling the biology behind the development of pancreatic cancer, there has been little change in the success of treating this devastating tumor [1].Pancreatic cancer is the fourth leading cause of cancer death in the USA with a median survival of only six months and a dismal five-year survival rate of 3%–5% [2,3,4]
The encapsulated cells were instilled through the Arteria pancreaticoduodenalis (A. gastroduodenalis) (Table 1)
More than one vessel had to be used for instillation of the encapsulated cells in only one patient in the first trial, but this was necessary in five patients in the second trial
Summary
Even though substantial progress has been made in unraveling the biology behind the development of pancreatic cancer, there has been little change in the success of treating this devastating tumor [1].Pancreatic cancer is the fourth leading cause of cancer death in the USA with a median survival of only six months and a dismal five-year survival rate of 3%–5% [2,3,4]. Even though substantial progress has been made in unraveling the biology behind the development of pancreatic cancer, there has been little change in the success of treating this devastating tumor [1]. 80%–85% of patients present with advanced non-resectable tumors that respond only poorly to most chemotherapeutic agents [5]. Recent evidence suggests that pancreatic cancer develops at a similar speed to other tumor types, and it has been estimated that it takes about 12 years from the start of tumorigenesis to the formation of a primary pancreatic cancer, with a further seven years being needed for the seeding and development of metastatic disease [6]. The primary tumor appears to be mix of genetically distinct subclones of which only one type gives rise to metastases, suggesting that the disease has a stem-cell origin [6,7]
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