TY - JOUR
T1 - Administration of oxaliplatin to patients with renal dysfunction
T2 - A preliminary report of the National Cancer Institute Organ Dysfunction Working Group
AU - Takimoto, Chris H.
AU - Remick, Scot C.
AU - Sharma, Sunil
AU - Mani, Sridhar
AU - Ramanathan, Ramesh K.
AU - Doroshow, James H.
AU - Hamilton, Anne
AU - Mulkerin, Daniel
AU - Graham, Martin
AU - Lockwood, Graham F.
AU - Ivy, Percy
AU - Egorin, Merrill
AU - Greenslade, Denis
AU - Goetz, Andrew
AU - Grem, Jean L.
N1 - Funding Information:
Supported in part by National Cancer Institute grant nos. U01CA069853, U01CA062502, U01CA069856, U01CA076642, U01CA062505, U01CA062491, and U01CA069855.
PY - 2003/8
Y1 - 2003/8
N2 - 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.
AB - 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.
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U2 - 10.1016/S0093-7754(03)00401-9
DO - 10.1016/S0093-7754(03)00401-9
M3 - Article
C2 - 14523791
AN - SCOPUS:0141993875
SN - 0093-7754
VL - 30
SP - 20
EP - 25
JO - Seminars in Oncology
JF - Seminars in Oncology
IS - 4 SUPPL. 15
ER -