Abstract
Purpose
To establish an appropriate administration schedule for oxaliplatin in FOLFOX plus bevacizumab therapy for a hemodialytic patient.
Methods
A 50-year-old man on chronic hemodialysis was treated for colon cancer and synchronous hepatic metastasis with modified FOLFOX-6 plus bevacizumab therapy every 3 weeks. The plasma concentration of free platinum was measured at eight points, before and within the first 50 h after oxaliplatin administration. A dose escalation study of oxaliplatin was performed at doses of 60, 70, and 85 mg/m2. A 4-h dialysis session was begun at the end of the oxaliplatin treatment.
Results
The pharmacokinetics of free platinum showed a bimodal pattern at each dose: The serum concentration decreased rapidly soon after dialysis, then increased, and remained at a high level for 24 h. The areas under the curves (AUC) for free platinum were 17.6, 23.6, and 32.6 μg h/mL after doses of 60, 70, and 85 mg/m2 oxaliplatin, respectively. These exceeded the AUC when 90 mg/m2 was given to a patient with normal renal function (7.9 μg h/mL). Treatment was safely continued for 6 months without severe toxicity.
Conclusion
FOLFOX plus bevacizumab therapy can be given safely to hemodialytic patients with no reduction in the dose of oxaliplatin if hemodialysis is performed soon after the administration of oxaliplatin and the dosing interval is extended to 3 weeks.
References
Maisonneuve P, Agodoa L, Gellert R et al (1999) Cancer in patients on dialysis for end-stage renal disease: an international collaborative study. Lancet 354:93–99
Hyodo I, Suzuki H, Takahashi K et al (2010) Present status and perspectives of colorectal cancer in Asia: colorectal cancer working group report at the 30th Asia-Pacific cancer conference. Jpn J Clin Oncol 40(Suppl 1):i38–i43
Hochster HS, Hart LL, Ramanathan RK et al (2008) Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol 26:3523–3529
Shitara K, Munakata M, Muto O et al (2007) Hepatic arterial infusion of oxaliplatin for a patient with hepatic metastases from colon cancer undergoing hemodialysis. Jpn J Clin Oncol 37:540–543
Matoba S, Sawada T, Toda S et al (2008) Modified FOLFOX6 in a patient on hemodialysis with metastatic colorectal cancer. Gan To Kagaku Ryoho 35:673–675 (in Japanese)
Watayo Y, Kuramochi H, Hayashi K et al (2010) Drug monitoring during FOLFOX6 therapy in a rectal cancer patient on chronic hemodialysis. Jpn J Clin Oncol 40:360–364
Takimoto CH, Remick SC, Sharma S et al (2003) Administration of oxaliplatin to patients with renal dysfunction: a preliminary report of the National Cancer Institute Organ Dysfunction Working Group. Semin Oncol 30:20–25
Heggie GD, Sommadossi JP, Cross DS, Huster WJ, Diasio RB (1987) Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine, and bile. Cancer Res 47:2203–2206
Takimoto CH, Remick SC, Sharma S et al (2003) Dose-escalating and pharmacological study of oxaliplatin in adult cancer patients with impaired renal function: a National Cancer Institute Organ Dysfunction Working Group Study. J Clin Oncol 21:2664–2672
Shirao K, Matsumura Y, Yamada Y et al (2006) Phase I study of single-dose oxaliplatin in Japanese patients with malignant tumors. Jpn J Clin Oncol 36:295–300
Schellens JHM, Ma J, Planting AST et al (1996) Relationship between the exposure to cisplatin, DNA-adduct formation in leucocytes and tumour response in patients with solid tumours. Br J Cancer 73:1569–1575
Jodrell DI, Egorin MJ, Canetta RM et al (1992) Relationships between carboplatin exposure and tumor response and toxicity in patients with ovarian cancer. J Clin Oncol 10:520–528
Graham MA, Lockwood GF, Greenslade D et al (2000) Clinical pharmacokinetics of oxaliplatin: a critical review. Clin Cancer Res 6:1205–1218
Calvert H, Judson I, van der Vijgh WJ (1993) Platinum complexes in cancer medicine: pharmacokinetics and pharmacodynamics in relation to toxicity and therapeutic activity. Cancer Surv 17:189–217
Massari C, Brienza S, Rotarski M et al (2000) Pharmacokinetics of oxaliplatin in patients with normal versus impaired renal function. Cancer Chemother Pharmacol 45:157–164
Watanabe R, Takiguchi Y, Moriya T et al (2003) Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer. Br J Cancer 88:25–30
Levi F, Metzger G, Massari C, Milano G (2000) Oxaliplatin: pharmacokinetics and chronopharmacological aspects. Clin Pharmacokinet 38:1–21
Takimoto CH, Graham MA, Lockwood G et al (2007) Oxaliplatin pharmacokinetics and pharmacodynamics in adult cancer patients with impaired renal function. Clin Cancer Res 13:4832–4839
Giacchetti S, Bjarnason G, Garufi C et al (2006) Phase III trial comparing 4-day chronomodulated therapy versus 2-day conventional delivery of fluorouracil, leucovorin, and oxaliplatin as first-line chemotherapy of metastatic colorectal cancer: the European Organisation for Research and Treatment of Cancer Chronotherapy group. J Clin Oncol 24:3562–3569
Kawazoe H, Sugishita H, Watanabe S et al (2010) Nephrotoxicity induced by repeated cycles of oxaliplatin in a Japanese colorectal cancer patient with moderate renal impairment. Gan To Kagaku Ryoho 37:1153–1157
Garnier-Viougeat N, Rixe O, Paintaud G et al (2007) Pharmacokinetics of bevacizumab in haemodialysis. Nephrol Dial Transplant 22:975
Acknowledgments
We thank Dr. Shigemi Matsumoto, Dr. Takafumi Nishimura, and Dr. Yoshiharu Sakai for their invaluable support in the conduct of this study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Horimatsu, T., Miyamoto, S., Morita, S. et al. Pharmacokinetics of oxaliplatin in a hemodialytic patient treated with modified FOLFOX-6 plus bevacizumab therapy. Cancer Chemother Pharmacol 68, 263–266 (2011). https://doi.org/10.1007/s00280-011-1633-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00280-011-1633-9