TY - JOUR
T1 - Chemotherapeutic agents eligible for prior dosing in pancreatic cancer patients requiring hemodialysis
T2 - A systematic review
AU - Hann, Alexander
AU - Nosalski, Evelyn
AU - Hermann, Patrick C.
AU - Egger, Jan
AU - Seufferlein, Thomas
AU - Keller, Frieder
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Aims: New chemotherapeutic agents prolong survival of patients with pancreatic ductal adenocarcinoma (PDAC). Although their incidence is rising, patients with end-stage renal disease (ESRD) requiring hemodialysis (HD) are not included in the phase III trials evaluating the effects of these chemotherapies. Many experts recommend applying chemotherapy after HD using a reduced dose. Alternatively, the concept of prior dosing allows for the application of dialyzable chemotherapeutic drugs using a normal dose, with an HD followed shortly after to mimic normal renal function. In this work, we provide guidance for clinicians on how to use chemotherapy in patients with PDAC on HD and how to identify substances suitable for prior dosing. Materials and methods: We systematically searched PubMed, from inception to September 2016, for published studies describing patients with ESRD on HD who received chemotherapies commonly applied in PDAC, including gemcitabine, fluorouracil (5-FU), capecitabine, oxaliplatin, irinotecan, docetaxel, erlotinib, sunitinib, S-1, and afatinib. Applied dosages, described toxicities, application time relative to HD, and pharmacokinetic measurements of the drug and its metabolites were assessed. Quantitative analysis of the drug plasma concentrations, including half-life during and in between HD and fraction of the drug eliminated during HD, were assessed. Results: We identified 56 studies describing 128 patients with ESRD undergoing HD during chemotherapeutic treatment. Quantitative pharmacokinetic analysis revealed that the following substances are dialyzable and thus suitable for application using the priordosing method: gemcitabine, 5-FU, oxaliplatin, irinotecan, and S-1. Conclusion: This work supports the application of dialyzable chemotherapeutic agents in patients with PDAC in standard dose when HD is performed shortly after the infusion.
AB - Aims: New chemotherapeutic agents prolong survival of patients with pancreatic ductal adenocarcinoma (PDAC). Although their incidence is rising, patients with end-stage renal disease (ESRD) requiring hemodialysis (HD) are not included in the phase III trials evaluating the effects of these chemotherapies. Many experts recommend applying chemotherapy after HD using a reduced dose. Alternatively, the concept of prior dosing allows for the application of dialyzable chemotherapeutic drugs using a normal dose, with an HD followed shortly after to mimic normal renal function. In this work, we provide guidance for clinicians on how to use chemotherapy in patients with PDAC on HD and how to identify substances suitable for prior dosing. Materials and methods: We systematically searched PubMed, from inception to September 2016, for published studies describing patients with ESRD on HD who received chemotherapies commonly applied in PDAC, including gemcitabine, fluorouracil (5-FU), capecitabine, oxaliplatin, irinotecan, docetaxel, erlotinib, sunitinib, S-1, and afatinib. Applied dosages, described toxicities, application time relative to HD, and pharmacokinetic measurements of the drug and its metabolites were assessed. Quantitative analysis of the drug plasma concentrations, including half-life during and in between HD and fraction of the drug eliminated during HD, were assessed. Results: We identified 56 studies describing 128 patients with ESRD undergoing HD during chemotherapeutic treatment. Quantitative pharmacokinetic analysis revealed that the following substances are dialyzable and thus suitable for application using the priordosing method: gemcitabine, 5-FU, oxaliplatin, irinotecan, and S-1. Conclusion: This work supports the application of dialyzable chemotherapeutic agents in patients with PDAC in standard dose when HD is performed shortly after the infusion.
KW - Chemotherapy
KW - Dialysis
KW - End-stage renal disease
KW - Pancreatic ductal adenocarcinoma
KW - Pharmacokinetic
UR - http://www.scopus.com/inward/record.url?scp=85049508067&partnerID=8YFLogxK
U2 - 10.5414/CN109327
DO - 10.5414/CN109327
M3 - Article
C2 - 29578402
AN - SCOPUS:85049508067
SN - 0301-0430
VL - 90
SP - 125
EP - 141
JO - Clinical Nephrology
JF - Clinical Nephrology
IS - 2
ER -