Médecine moléculaire et génétique

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

Abstract

Osawa H

Aim: We investigated the safety and feasibility of L-OHP with chronic renal failure (CRF) on hemodialysis (HD) patients by examining the influence of pharmacokinetics and pharmacodynamics of oxaliplatin (L-OHP). Furthermore, we investigated.

Methods: We present the results of three patients who were treated with modified FOLFOX6 (mFOLFOX6) chemotherapy for a mCRC with chronic renal failure on HD. We measured their plasma concentration of total platinum and free platinum. We evaluated whether L-OHP dose could be safely used for these patients. Different starting dose of L-OHP and 5-fluorouracil (50% and 75%) were used in these patients. Pharmacokinetics monitoring of platinum in plasma, plasma ultrafiltrates were measured these time schedule follow as: pre-chemotherapy infusion and 4 hours (pre-HD), 6 hours (half of HD), 8 hours (post HD), 48 hours after.

Results: The 50% of peak concentrations (Cmax) was 0.27 μg・hr/mL ± 0.02 μg/mL and 75% Cmax was 0.41 μg・hr/mL ± 0.02 μg/mL. 50% of the area under the concentration versus time curve (AUC) was 14.8 μg・hr/mL ± 1.22 μg・hr/mL and 75% AUC was 22.43 μg・hr/mL ± 0.85 μg・hr/mL.

Conclusion: We recognized these free plasma concentration which 50% dose of L-OHP was similar AUC between healthy and CRF patients. L-OHP pharmacokinetics and pharmacodynamics are altered in patients with CRF, but corresponding increase in L-OHP related hematological and non-hematological toxicities is not observed. It is important for cancer patients with CRF that the feasibility and efficacy of L-OHP combined chemotherapy should be determined.