From the Guidelines
Carboplatin is the recommended alternative chemotherapy agent for bladder cancer when cisplatin cannot be used due to pre-existing hearing loss.
Rationale
The recommendation is based on the most recent and highest quality study available, which suggests that carboplatin can be used as a substitute for cisplatin in patients with bladder cancer who are not eligible for cisplatin due to comorbidities such as hearing loss 1.
Clinical Considerations
- Carboplatin can be administered in combination with gemcitabine as part of a regimen typically given every 21 days for 3-6 cycles, depending on the specific clinical situation.
- The standard dosing for carboplatin is often calculated using the Calvert formula (AUC 4-5) while gemcitabine is typically given at 1000 mg/m² on days 1 and 8 of each cycle.
- This substitution is appropriate because cisplatin is known to cause ototoxicity and can worsen pre-existing hearing loss, whereas carboplatin has a more favorable ototoxicity profile.
- While carboplatin is generally considered less nephrotoxic and ototoxic than cisplatin, it is essential to note that it may be slightly less effective in some bladder cancer settings.
- Regular audiometric testing may still be warranted during treatment, and renal function should be monitored as carboplatin dosing depends on kidney function.
- For patients with both hearing loss and poor renal function, non-platinum regimens or immunotherapy options might need to be considered based on the specific disease characteristics and patient factors.
Supporting Evidence
The European Society for Medical Oncology (ESMO) clinical practice guidelines for bladder cancer recommend gemcitabine-carboplatin as a treatment option for cisplatin-ineligible patients with advanced urothelial cancer 1. Additionally, the National Comprehensive Cancer Network (NCCN) guidelines suggest that carboplatin can be used as an alternative to cisplatin in patients with bladder cancer who are not eligible for cisplatin due to comorbidities such as hearing loss 1. Overall, the available evidence supports the use of carboplatin as a viable alternative to cisplatin in patients with bladder cancer who are not eligible for cisplatin due to pre-existing hearing loss.
From the FDA Drug Label
KEYTRUDA may be used alone when your bladder or urinary tract cancer: has spread or cannot be removed by surgery (advanced urothelial cancer), and you are not able to receive chemotherapy that contains platinum (medicines called either cisplatin or carboplatin), The alternative chemotherapy agent that can be used for bladder cancer if cisplatin cannot be used due to pre-existing hearing loss (ototoxicity) is carboplatin.
From the Research
Alternative Chemotherapy Agents for Bladder Cancer
If cisplatin cannot be used due to pre-existing hearing loss (ototoxicity), several alternative chemotherapy agents can be considered for bladder cancer treatment. These include:
- Carboplatin: a platinum-based agent that can be used in patients who are ineligible for cisplatin-based chemotherapy due to renal impairment, symptomatic cardiac disease, or poor performance status 2, 3, 4, 5
- Gemcitabine: a non-platinum-based agent that has shown effectiveness in combination with other agents, such as paclitaxel and cisplatin, in the treatment of advanced urothelial carcinoma 2, 6
- Paclitaxel: a non-platinum-based agent that has been used in combination with gemcitabine and cisplatin in the treatment of advanced urothelial carcinoma 2, 6
- Pemetrexed and vinflunine: non-platinum-based agents that have shown small but demonstrable overall survival benefits in the treatment of bladder cancer 2
Eligibility Criteria for Alternative Chemotherapy Agents
The eligibility criteria for alternative chemotherapy agents, such as carboplatin, split-dose cisplatin, and gemcitabine-based regimens, vary depending on factors such as renal function, performance status, and hematological parameters 5. For example: