From the Guidelines
For patients with impaired renal function, carboplatin and gemcitabine is generally the better option compared to cisplatin and gemcitabine. This recommendation is based on the most recent and highest quality study available, which highlights the importance of considering renal function when selecting chemotherapy regimens for patients with advanced urothelial carcinoma 1.
Key Considerations
- Carboplatin has less nephrotoxicity than cisplatin and can be dosed according to renal function using the Calvert formula (based on target AUC and glomerular filtration rate) 1.
- Gemcitabine dosing should also be adjusted in renal impairment, typically starting with reduced doses (such as 75-100% of standard dose for mild impairment, and further reductions for moderate impairment) 1.
- The specific degree of dose reduction depends on the severity of renal dysfunction, with creatinine clearance being the key parameter for adjustment 1.
Rationale
Cisplatin is highly nephrotoxic and can further damage already compromised kidneys, potentially leading to acute kidney injury or worsening of chronic kidney disease 1.
Monitoring and Dose Adjustments
Regular monitoring of renal function before each cycle is essential with either regimen, but particularly important if carboplatin is selected to ensure appropriate dose calculations 1.
Emerging Treatment Options
Recent studies have explored the use of immunotherapy agents, such as atezolizumab and pembrolizumab, as first-line treatment options for patients with advanced urothelial carcinoma who are not eligible for cisplatin-based therapy 1. However, the use of these agents is restricted to patients with specific PD-L1 expression levels or those who are not eligible for any platinum-containing chemotherapy 1.
From the Research
Treatment Options for Patients with Impaired Renal Function
When considering treatment options for patients with impaired renal function, the choice between cisplatin and gemcitabine or carboplatin and gemcitabine is crucial. The following points highlight the key aspects of these treatment options:
Cisplatin and Gemcitabine:
- A study published in 2015 2 found that gemcitabine plus split-dose cisplatin could be a promising alternative to gemcitabine plus carboplatin for cisplatin-unfit patients with advanced urothelial carcinoma.
- Another study from 2012 3 evaluated the safety and efficacy of gemcitabine and a split dose administration of cisplatin in patients with renal dysfunction, showing that this regimen is active and feasible in this subset of patients.
- A feasibility study from 2006 4 proved that a gemcitabine and low-dose cisplatin regimen, delivered every two weeks, is safe and feasible in patients with impaired renal function.
Carboplatin and Gemcitabine:
- A study from 2006 5 evaluated the activity and toxicity of gemcitabine and carboplatin in patients with advanced urothelial transitional carcinoma, including those with impaired renal function, and found that this combination is powerful for first-line therapy.
- Another study published in 2003 6 found that the gemcitabine/carboplatin combination achieves a similar result to doublets using cisplatin, with an acceptable toxicity profile, and enables patients with impaired renal function to be treated.
- The same study from 2006 5 also noted that decreases of effectiveness in cases of impaired renal function were not detected, and the chemotherapy combination of gemcitabine and carboplatin is definitely powerful for a first-line-therapy in patients with advanced TCC.
Comparison of Treatment Options
- Both cisplatin and gemcitabine, and carboplatin and gemcitabine, have been shown to be effective treatment options for patients with impaired renal function.
- The choice between these two options may depend on individual patient factors, such as the severity of renal impairment and overall health status.
- Further research is needed to determine the optimal treatment approach for patients with impaired renal function.