Administration of oxaliplatin to patients with renal dysfunction: A preliminary report of the National Cancer Institute Organ Dysfunction Working Group

Chris H. Takimoto, Scot C. Remick, Sunil Sharma, Sridhar Mani, Ramesh K. Ramanathan, James H. Doroshow, Anne Hamilton, Daniel Mulkerin, Martin Graham, Graham F. Lockwood, Percy Ivy, Merrill Egorin, Denis Greenslade, Andrew Goetz, Jean L. Grem

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Oxaliplatin is an approved agent with clinical activity in the treatment of advanced colorectal cancer. Preliminary pharmacokinetic evidence suggests that oxaliplatin is predominantly cleared by renal excretion; however, formal dosing guidelines in patients with renal impairment are lacking. The National Cancer Institute Organ Dysfunction Working Group initiated the following dose-escalation pharmacokinetic trial of oxaliplatin in patients with varying degrees of renal function. Thirty-seven patients with various solid tumor malignancies were stratified into four renal dysfunction groups based on their measured 24-hour urinary creatinine clearance (CrCL). Patients in group A (controls) all had a CrCL ≥ 60 mL/min; group B patients had mild renal dysfunction with CrCLs ranging from 40 to 59 mL/min; group C patients had moderate renal dysfunction with CrCLs of 20 to 39 mL/min; and patients with a CrCL < 20 mL/min were entered into the group D severe cohort. The starting oxaliplatin dose for patients in the normal group A was 130 mg/m2, while lower doses of 105, 80, and 60 mg/m2 were used in groups B, C, and D, respectively. Patients received a 2-hour intravenous infusion of oxaliplatin every 3 weeks, and doses were escalated in cohorts of three patients in each renal dysfunction group in the absence of any severe dose-limiting toxicity. Oxaliplatin-associated platinum pharmacokinetics were monitored in both plasma (bound + unbound) and plasma ultrafiltrates (unbound). Full single-agent doses of oxaliplatin of 130 mg/m2 were well tolerated by patients with normal, mild, and moderate renal dysfunction in groups A, B, and C, respectively. Only one patient was enrolled in group D. Unbound platinum clearance significantly correlated with CrCL (r = .884), but the increased systemic exposures to circulating platinum were not associated with increased clinical toxicities. These data suggest that dose reductions of single-agent oxaliplatin are not necessary in patients with CrCLs >20 mL/min.

Original languageEnglish (US)
Pages (from-to)20-25
Number of pages6
JournalSeminars in Oncology
Volume30
Issue number4 SUPPL. 15
DOIs
StatePublished - Aug 2003

ASJC Scopus subject areas

  • Hematology
  • Oncology

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    Takimoto, C. H., Remick, S. C., Sharma, S., Mani, S., Ramanathan, R. K., Doroshow, J. H., Hamilton, A., Mulkerin, D., Graham, M., Lockwood, G. F., Ivy, P., Egorin, M., Greenslade, D., Goetz, A., & Grem, J. L. (2003). Administration of oxaliplatin to patients with renal dysfunction: A preliminary report of the National Cancer Institute Organ Dysfunction Working Group. Seminars in Oncology, 30(4 SUPPL. 15), 20-25. https://doi.org/10.1016/S0093-7754(03)00401-9