What is the dose adjustment for the VTD (Velcade, Thalidomide, Dexamethasone)-PACE chemotherapy regimen in a patient with impaired renal function, specifically a creatinine clearance of 37?

From the Guidelines

For a patient with a creatinine clearance of 37 mL/min receiving VTD-PACE chemotherapy, dose adjustments are necessary for several medications in the regimen, prioritizing the reduction of cisplatin and cyclophosphamide to minimize renal toxicity and ensure optimal treatment outcomes in terms of morbidity, mortality, and quality of life. When considering dose adjustments for a patient with impaired renal function, it is crucial to prioritize medications that are primarily excreted by the kidneys. According to the most recent evidence 1, in patients with renal impairment, cisplatin is usually omitted from the regimen due to its high nephrotoxicity, and cyclophosphamide should be dose-adjusted for kidney function. Given the patient's creatinine clearance of 37 mL/min, the following adjustments can be considered:

• Cisplatin should be omitted or reduced significantly, as its use is generally avoided when GFR < 30 ml/min/1.73 m2, as suggested by guidelines 1.
• Cyclophosphamide should be reduced by 25% (to approximately 300 mg/m²/day), considering its dose adjustment for renal impairment.
• Etoposide may require a reduction, but specific guidelines for dose adjustment in renal impairment are less clear; however, a 25% reduction (to approximately 30 mg/m²/day) could be considered based on general principles of renal adjustment.
• Doxorubicin typically requires no adjustment at this level of renal function.
• For bortezomib (the "V" component), no dose adjustment is needed as it's primarily metabolized by the liver.
• Thalidomide (the "T") and dexamethasone (the "D") also require no renal adjustments. It's essential to monitor the patient closely for signs of toxicity, particularly myelosuppression and neurotoxicity, which may be exacerbated with impaired renal function. Regular assessment of renal function during treatment is crucial, as further deterioration may necessitate additional dose modifications. Adequate hydration and potentially using nephroprotective measures should be considered to prevent further kidney injury during chemotherapy administration.

From the Research

Dose Adjustment for VTD-PACE Chemotherapy Regimen

The VTD-PACE chemotherapy regimen consists of Velcade, Thalidomide, Dexamethasone, cisplatin, etoposide, and cyclophosphamide. To determine the dose adjustment for a patient with impaired renal function, specifically a creatinine clearance of 37, we need to consider the dosing recommendations for each drug.

Renal Function and Chemotherapy

• Renal function is monitored during chemotherapy because chemotherapeutic drugs are excreted by the kidneys and are potentially nephrotoxic 2.
• Doses are adjusted according to the glomerular filtration rate (GFR), i.e., the more reduced the GFR, the lower the treatment dose 2.
• However, there is limited data on the adherence of physicians to dosing recommendations for these drugs in cancer patients with renal impairment 3.

Dose Adjustment for Individual Drugs

• Cisplatin is contraindicated in patients with a creatinine clearance < 60 mL/min, but dose reduction is not explicitly stated for a creatinine clearance of 37 3.
• Etoposide dosage should be reduced in patients with a creatinine clearance from 15 to 50 mL/min, but the exact dose reduction is not specified 3.
• Thalidomide and Velcade do not have explicit dose adjustments for renal impairment in the provided studies.
• Dexamethasone does not require dose adjustment for renal impairment.

Clinical Implications

• The studies suggest that dose adjustments for chemotherapy drugs in patients with renal impairment are not always made as recommended 3, 2.
• Measured creatinine clearance is a more reliable indicator of renal function than predicted creatinine clearance 4.
• The Cockcroft-Gault formula may not be accurate for estimating creatinine clearance in all patients 4.

Specific Dose Adjustment for Creatinine Clearance of 37

• Based on the available studies, it is not possible to provide a specific dose adjustment for the VTD-PACE chemotherapy regimen in a patient with a creatinine clearance of 37, as the studies do not provide explicit dose reduction recommendations for this level of renal impairment.
• However, it is clear that dose adjustments should be made based on the individual patient's renal function, and that measured creatinine clearance is a more reliable indicator of renal function than predicted creatinine clearance 3, 2, 4.