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. According to the NCCN guidelines [ 1 ], carboplatin can be substituted for cisplatin in the metastatic setting for cisplatin-ineligible patients, such as those with a GFR less than 60 mL/min. The recommended regimen is carboplatin in combination with gemcitabine, with carboplatin dosed at AUC 4-5 intravenously on day 1 and gemcitabine at 1000 mg/m² on days 1 and 8 of a 21-day cycle [ 1 ]. This regimen is generally continued for 4-6 cycles depending on response and tolerability.
Key Considerations
- Carboplatin is preferred in patients with renal impairment (creatinine clearance <60 mL/min), hearing loss, neuropathy, or poor performance status that would make cisplatin unsuitable [ 1 ].
- While carboplatin is better tolerated than cisplatin, it is considered somewhat less effective in bladder cancer [ 1 ].
- Other potential alternatives include single-agent gemcitabine, paclitaxel, or immunotherapy agents like pembrolizumab or atezolizumab, particularly in cisplatin-ineligible patients with PD-L1 positive tumors [ 1 ].
- The choice between these alternatives should be based on the patient's specific contraindications to cisplatin, comorbidities, performance status, and disease characteristics [ 1 ].
Treatment Approach
- Patients with metastatic disease are re-evaluated after 2 to 3 cycles of chemotherapy, and treatment is continued for 2 more cycles in patients whose disease responds or remains stable [ 1 ].
- Chemotherapy may be continued for a maximum of 6 cycles, depending on response [ 1 ].
- If no response is noted after 2 cycles or if significant morbidities are encountered, a change in therapy is advised, taking into account the patient’s current performance status, extent of disease, and specific prior therapy [ 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.