Cisplatin Dosing in Liver Impairment
No dose adjustment is required for cisplatin in patients with liver impairment, as cisplatin undergoes predominantly renal elimination and is not significantly metabolized by the liver. 1, 2
Primary Recommendation
- Cisplatin can be administered at standard doses in patients with hepatic dysfunction, including those with liver metastases causing significant hepatic impairment 1
- Standard dosing regimens remain appropriate: 100 mg/m² every 3 weeks, 60-80 mg/m² every 3-4 weeks, or 40 mg/m² weekly, depending on the indication and concurrent therapy 3, 4
Evidence Supporting Use in Liver Dysfunction
- A retrospective analysis of 14 patients with solid tumors and liver dysfunction induced by metastases demonstrated that cisplatin monotherapy was well-tolerated with acceptable toxicity profiles 1
- Cisplatin is classified among agents that are "relatively well tolerated" in hepatic failure, unlike taxanes, vinca alkaloids, irinotecan, and anthracyclines which require significant dose reductions 2
- The drug's elimination is primarily renal (>90%), making hepatic metabolism a negligible factor in its clearance 2, 5
Critical Monitoring Requirements
Renal function must be closely monitored, as this is the primary safety concern with cisplatin, not hepatic function 3:
- Do not administer repeat courses until serum creatinine is <1.5 mg/100 mL and BUN is <25 mg/100 mL 4
- Mandatory pretreatment hydration with 1-2 liters of fluid infused for 8-12 hours prior to dosing 4
- Post-treatment hydration is essential to prevent renal toxicity 3
Important Caveats in Liver Dysfunction
Cirrhotic patients often have impaired renal function despite normal serum creatinine levels 5:
- Measure or estimate creatinine clearance directly in cirrhotic patients, as serum creatinine alone is unreliable 5
- Creatinine clearance tends to overestimate glomerular filtration in cirrhotic patients, so clinical monitoring remains essential 5
Monitor for hepatotoxicity as a drug effect, not as a contraindication 6, 7:
- Cisplatin itself can cause transient hepatotoxicity with elevations in AST, ALT, alkaline phosphatase, and LDH 6
- These elevations typically occur on day 2 of treatment and resolve by day 10 6
- Oxidative stress-mediated liver injury has been documented in preclinical studies 7
Hematologic Monitoring
- Ensure platelets ≥100,000/mm³ and WBC ≥4,000/mm³ before each cycle 4
- Patients with liver dysfunction from metastases experienced grade III hematological toxicity in approximately 40% of cases, which was manageable 1
Alternative Considerations
If cisplatin cannot be used due to renal dysfunction (not hepatic dysfunction):
- Carboplatin may be substituted, though it is inferior in efficacy for most indications 3
- For bladder cancer specifically, carboplatin-based regimens showed response rates of only 26-42% in patients with renal impairment 3
Clinical Outcome Data
- In the cohort of patients with liver dysfunction treated with cisplatin monotherapy, 6 of 14 patients achieved partial remission, and 6 were able to transition to combination chemotherapy after liver function improvement 1
- Median overall survival was 4.8 months in this heavily pretreated population with advanced metastatic disease 1