From the Guidelines
Carboplatin is the primary alternative chemotherapy agent for bladder cancer when cisplatin cannot be used due to impaired renal function or other contraindications. This is based on the most recent evidence from the NCCN clinical practice guidelines in oncology, which recommends carboplatin as a category 2B alternative first-line regimen for metastatic bladder cancer 1.
Key Points to Consider
- The choice of alternative chemotherapy agent should be based on the patient's specific contraindication to cisplatin, overall health status, and disease characteristics.
- Carboplatin is typically administered in combination with gemcitabine as part of a regimen called CG (carboplatin-gemcitabine), with a standard dosing of carboplatin AUC 5 on day 1 and gemcitabine 1000 mg/m² on days 1 and 8 of a 21-day cycle 1.
- Other alternatives include single-agent gemcitabine or immunotherapy options such as atezolizumab or pembrolizumab, especially for patients with high PD-L1 expression 1.
- For patients with significant comorbidities who cannot tolerate combination chemotherapy, dose reductions or weekly regimens may be considered.
Important Considerations
- The performance status of the patient is a major determinant in the selection of a regimen, with regimens having lower toxicity profiles recommended in patients with compromised liver or renal status or serious comorbid conditions 1.
- The use of checkpoint inhibitors, such as atezolizumab or pembrolizumab, is recommended as a first-line option in certain patients, including those who are not cisplatin-eligible and whose tumors express PD-L1 1.
- Clinical trial enrollment is recommended for all patients when appropriate, but is strongly recommended for second-line and subsequent therapies 1.
From the Research
Alternative Chemotherapy Agents for Bladder Cancer
In cases where Cisplatin (Platinum-based chemotherapy) cannot be used due to impaired renal function or other contraindications, several alternative chemotherapy agents can be considered. These include:
- Paclitaxel
- Gemcitabine
- Carboplatin
- Pemetrexed
- Vinflunine
Combination Therapies
Some studies have investigated the effectiveness of combination therapies, such as:
- Gemcitabine plus carboplatin
- Gemcitabine plus paclitaxel
- Methotrexate, carboplatin, and vinblastine (M-CAVI) These combinations have shown promise in treating bladder cancer in patients who are ineligible for cisplatin-based chemotherapy 2, 3, 4.
Efficacy and Tolerability
The efficacy and tolerability of these alternative chemotherapy agents and combination therapies have been evaluated in various studies. For example, a Phase II trial of M-CAVI showed a response rate of 48% and a median duration of response of 7 months in patients with metastatic or locally advanced bladder cancer 3. Another study found that the combination of gemcitabine, paclitaxel, and cisplatin was highly effective and tolerable in patients with advanced urothelial carcinoma, with an overall response rate of 81% and a median actuarial survival of 22 months 5.
Considerations for Patients with Impaired Renal Function
For patients with impaired renal function, the use of cisplatin-based chemotherapy may be limited. However, some studies suggest that carboplatin-based combinations may be a viable alternative, and that the perception of their inferiority to cisplatin-based combinations may be incorrect 6. Further research is needed to specifically examine chemotherapy in patients with bladder cancer and renal impairment 2, 4, 6.