Oxaliplatin pharmacokinetics and pharmacodynamics in adult cancer patients with impaired renal function

University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Clinical Cancer Research (Impact Factor: 8.19). 08/2007; 13(16):4832-9. DOI: 10.1158/1078-0432.CCR-07-0475
Source: PubMed

ABSTRACT To characterize the pharmacokinetics and pharmacodynamics of oxaliplatin in cancer patients with impaired renal function.
Thirty-four patients were stratified by 24-h urinary creatinine clearance (CrCL) into four renal dysfunction groups: group A (control, CrCL, >or=60 mL/min), B (mild, CrCL, 40-59 mL/min), C (moderate, CrCL, 20-39 mL/min), and D (severe, CrCL, <20 mL/min). Patients were treated with 60 to 130 mg/m2 oxaliplatin infused over 2 h every 3 weeks. Pharmacokinetic monitoring of platinum in plasma, plasma ultrafiltrates, and urine was done during cycles 1 and 2.
Plasma ultrafiltrate platinum clearance strongly correlated with CrCL (r2 = 0.712). Platinum elimination from plasma was triphasic, and maximal platinum concentrations (Cmax) were consistent across all renal impairment groups. However, only the beta-half-life was significantly prolonged by renal impairment, with values of 14.0 +/- 4.3, 20.3 +/- 17.7, 29.2 +/- 29.6, and 68.1 h in groups A, B, C, and D, respectively (P = 0.002). At a dose level of 130 mg/m2, the area under the concentration time curve increased in with the degree of renal impairment, with values of 16.4 +/- 5.03, 39.7 +/- 11.5, and 44.6 +/- 14.6 mug.h/mL, in groups A, B, and C, respectively. However, there was no increase in pharmacodynamic drug-related toxicities. Estimated CrCL using the Cockcroft-Gault method approximated the measured 24-h urinary CrCL (mean prediction error, -5.0 mL/min).
Oxaliplatin pharmacokinetics are altered in patients with renal impairment, but a corresponding increase in oxaliplatin-related toxicities is not observed.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal cancer is a common cancer in older patients with nearly 70% of all cases diagnosed in patients 65 years and older. Many chemotherapy clinical trials that have advanced the field in both localized and metastatic disease have not included patients from the age group most representative of the disease. Retrospective series and subset analyses show that older patients derive the same benefit from optimum multimodality strategies as their younger counterparts. Lack of prospective data and a generalization of increased toxicity rates seen in older patients with multiple comorbidities to the overall heterogenous population of older patients have lead to a reluctance to treat older patients with modern chemobiologic therapy. Despite increased comorbidities, decreased hepatic reserve, and an under-representation of older patients undergoing liver resection, the majority of published data does not support a negative correlation between poor outcome and increasing age. There is an urgent need to include older patients in clinical trials for colorectal cancer and to understand and use geriatric assessment scoring systems to identify those patients most likely to benefit from optimum treatment.
    The Cancer Journal 01/2010; 16(3):241-52. DOI:10.1097/PPO.0b013e3181e07690 · 3.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In oncology, special populations are generally excluded from studies of investigational agents because dosing or scheduling information is limited or unknown. Patients who are members of special populations may be considered too frail to tolerate therapy. Special population study subjects may have hepatic or renal dysfunction from a variety of etiologies or may have poor performance status. Children and young adults represent another patient group with limited access to new agents. They are often excluded due to unique concerns about arresting or impeding their growth or development; their unique risks create an ethical dilemma in many cases. These populations are addressed in the following pages. This chapter’s emphasis is on ways to approach the study of special populations and on issues of greatest concern for investigators.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cancer is a disease of aging; approximately 60% of all cancers and 70% of cancer mortality occur in persons aged 65 years and over. Aging is a highly individualized process, characterized by physiologic and psychosocial changes that can affect tolerance to treatment. Older patients are a highly heterogeneous group, with varying levels of risk for functional or physical decline and mortality. Historically, clinical trials have not reflected the general population of older cancer patients due to the low numbers of older patients included and the strict inclusion criteria for healthy, “fit” older adults [1]. Therefore, the majority of patients aged 65 years and older with cancer are treated based on data derived from clinical trials that often describe the effects of treatment on the median-age population enrolled in the studies or on the elderly with good performance status.
    01/1970: pages 201-261;