Oxaliplatin Pharmacokinetics and Pharmacodynamics in Three Metastatic Colorectal Cancer Patients with Hemodialysis

The metastatic colorectal cancer (mCRC) is highly mortality disease in the USA, EU and Asia. Recently, we have been developing many cytotoxic agents and monoclonal antibodies such as oxaliplatin (L-OHP), irinotecan (CPT-11), 5-fluorouracil (5-FU), capecitabine (Cap), S-1, anti-VEGF antibody and anti-EGF receptor (EGFR) antibody. These combined chemotherapy are widely accepted as first-line treatment with mCRC. L-OHP is a key anti-cancer drug for gastrointestinal cancer [1-3]. L-OHP quick converts to highly reactive monochloroplatinum, dichloroplatinum and diaquoplatinum biotransformation products [4] which can immediately interact with tissue, proteins and other plasma constituents [5]. The L-OHP associated platinum in plasma ultrafiltrates is huge size (>300 L) and the kinetics of elemental platinum in plasma after L-OHP administration shows three distinct phases. First, there is a short α-phase half-life of 0.25 to 0.33 hours (hrs) followed by a longer β-phase half-life of almost 16 hrs. Finally, highly sensitive analytic methods, such as inductively coupled plasma mass spectroscopy, show measure a prolonged γ-half-life of 240 to over 600 hrs. Furthermore, initial 48 hrs after drug administration, over 50% of the administrated platinum is excreted into the urine, consist with kidneys being a main route of platinum elimination [5,6]. When we have been repeating infusion, L-OHP accumulate in erythrocytes. Finally, this intracellular binding within red blood cell is thought to be irreversible [7,8]. Actually, pharmacokinetics and pharmacodynamics in patients with hemodialysis (HD) differs from that patients with normal kidney function, chemotherapy for a hemodialysis patient should be careful to administer. We treated chemotherapy of modified FOLFOX6 (mFOLFOX6) to three mCRC patients with HD who measured oxaliplatin (L-OHP) pharmacokinetics and pharmacodynamics. We investigated a dose-escalating pharmacologic *Corresponding authors: Hiroshi Osawa, Department of Oncology and Hematology, Edogawa Hospital, 2-24-18 Higashi-koiwa, Edogawa, Tokyo 1330052, Japan, Tel: 0336731221; Fax: 0336731229; E-mail: [email protected]