Phase I and Pharmacokinetic Study of Pemetrexed Administered Every 3 Weeks to Advanced Cancer Patients With Normal and Impaired Renal Function

2006 ◽  
Vol 24 (4) ◽  
pp. 552-562 ◽  
Author(s):  
Alain C. Mita ◽  
Christopher J. Sweeney ◽  
Sharyn D. Baker ◽  
Andrew Goetz ◽  
Lisa A. Hammond ◽  
...  

Purpose This phase I study was conducted to determine the toxicities, pharmacokinetics, and recommended doses of pemetrexed in cancer patients with normal and impaired renal function. Patients and Methods Patients received a 10-minute infusion of 150 to 600 mg/m2 of pemetrexed every 3 weeks. Patients were stratified for independent dose escalation by measured glomerular filtration rate (GFR) into four cohorts ranging from ≥ 80 to less than 20 mL/min. Pemetrexed plasma and urine pharmacokinetics were evaluated for the first cycle. Patients enrolled after December 1999 were supplemented with oral folic acid and intramuscular vitamin B12. Results Forty-seven patients were treated with 167 cycles of pemetrexed. Hematologic dose-limiting toxicities occurred in vitamin-supplemented patients (two; 15%) and nonsupplemented patients (six; 18%), and included febrile neutropenia (four patients) and grade 4 thrombocytopenia (two patients). Nonhematologic toxicities included fatigue, diarrhea, and nausea, and did not correlate with renal function. Accrual was discontinued in patients with GFR less than 30 mL/min after one patient with a GFR of 19 mL/min died as a result of treatment-related toxicities. Pemetrexed plasma clearance positively correlated with GFR (r2 = 0.736), resulting in increased drug exposures in patients with impaired renal function. With vitamin supplementation, pemetrexed 600 mg/m2 was tolerated by patients with a GFR ≥ 80 mL/min, whereas patients with a GFR of 40 to 79 mL/min tolerated a dose of 500 mg/m2. Conclusion Pemetrexed was well tolerated at doses of 500 mg/m2 with vitamin supplementation in patients with GFR ≥ 40 mL/min. Additional studies are needed to define appropriate dosing for renally impaired patients receiving higher dose pemetrexed with vitamin supplementation.

2016 ◽  
Vol 78 (6) ◽  
pp. 1185-1197 ◽  
Author(s):  
Analía Azaro ◽  
Jordi Rodón ◽  
Jean-Pascal Machiels ◽  
Sylvie Rottey ◽  
Silvia Damian ◽  
...  

1982 ◽  
pp. 633-639 ◽  
Author(s):  
Joaquim Gouveia ◽  
Patricia Ribaud ◽  
Antoine Goutner ◽  
Georges Mathé

2013 ◽  
Vol 71 (Suppl 3) ◽  
pp. 202.1-202
Author(s):  
P. Martin ◽  
S. Oliver ◽  
M. Gillen ◽  
T. Marbury ◽  
D. Millson

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 3214-3214 ◽  
Author(s):  
J. L. Steinberg ◽  
D. S. Mendelson ◽  
H. Block ◽  
S. B. Green ◽  
V. S. Shu ◽  
...  

2016 ◽  
Vol 107 (5) ◽  
pp. 590-600 ◽  
Author(s):  
Satoru Iwasa ◽  
Yasuhide Yamada ◽  
Yuji Heike ◽  
Hirokazu Shoji ◽  
Yoshitaka Honma ◽  
...  

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