Dose-Escalating and Pharmacological Study of Oxaliplatin in Adult Cancer Patients With Impaired Renal Function: A National Cancer Institute Organ Dysfunction Working Group Study
| Autor: | Martin C. Graham, Sunil Sharma, Jean L. Grem, Denis Greenslade, Ronald Knight, Graham F. Lockwood, Percy Ivy, Scot C. Remick, Andrew Goetz, Rebecca Thomas, James H. Doroshow, Chris H. Takimoto, Barbara Schuler, Brian P. Monahan, A. Hamilton, William Dahut, Merrill J. Egorin, Daniel Mulkerin, Sridhar Mani, Ramesh K. Ramanathan |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Maximum Tolerated Dose Organoplatinum Compounds medicine.medical_treatment Urology Renal function Kidney Function Tests Risk Assessment Severity of Illness Index Drug Administration Schedule Pharmacokinetics Reference Values Neoplasms Severity of illness medicine Humans Infusions Intravenous Aged Neoplasm Staging Probability Aged 80 and over Chemotherapy Dose-Response Relationship Drug business.industry Organ dysfunction Middle Aged medicine.disease Survival Analysis United States Oxaliplatin Surgery Treatment Outcome National Institutes of Health (U.S.) Oncology Pharmacodynamics Female Kidney Diseases medicine.symptom business Follow-Up Studies Glomerular Filtration Rate Kidney disease medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 21:2664-2672 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2003.11.015 |
| Popis: | Purpose: This study was undertaken to determine the toxicities, pharmacokinetics, and maximum tolerated doses of oxaliplatin in patients with renal impairment and to develop formal guidelines for oxaliplatin dosing in this patient population. Patients and Methods: Thirty-seven adult cancer patients with variable renal function received intravenous oxaliplatin at 60 to 130 mg/m2 every 3 weeks. Patients were stratified by 24-hour creatinine clearance (CrCL) into four cohorts: group A (controls, CrCL ≥60 mL/min), group B (mild dysfunction, CrCL 40 to 59 mL/min), group C (moderate dysfunction, CrCL 20 to 39 mL/min), and group D (severe dysfunction, CrCL Results: No dose-limiting toxicities were observed in any patient group during the first cycle of therapy. Escalation of oxaliplatin to the maximum dose of 130 mg/m2 was well tolerated in all patient groups with a CrCL ≥20 mL/min (groups A, B, and C). Pharmacokinetic analysis showed that patients with decreased CrCL had a corresponding decrease in the clearance of plasma ultrafiltrable platinum (r2 = 0.765). However, oxaliplatin-induced side effects were not more common or severe in patients with mild to moderate renal dysfunction, despite the decrease in ultrafiltrable platinum clearance. Conclusion: Oxaliplatin at 130 mg/m2 every 3 weeks is well tolerated by patients with mild to moderate degrees of renal dysfunction. These data strongly support the recommendation that dose reductions of single-agent oxaliplatin are not necessary in patients with a CrCL greater than 20 mL/min. |
| Databáze: | OpenAIRE |
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