Cisplatin Safety in Elderly Patients
Cisplatin can be safely administered to elderly patients, but chronological age alone should not determine eligibility—instead, biological fitness, renal function (creatinine clearance ≥50 mL/min), and comorbidities must guide the decision, with geriatric screening tools used to assess frailty rather than arbitrary age cutoffs. 1
Key Safety Considerations
Age Is Not an Absolute Contraindication
- Chronological age alone should not be a determining factor for cisplatin eligibility because fit older patients have been shown to receive comparable clinical benefits to younger patients when receiving full-dose treatment. 1
- Some centers refuse cisplatin to patients >70 years based on older meta-analyses, but geriatric screening assessments to determine biological fitness are more appropriate than arbitrary age cutoffs. 1
- A 1992 study demonstrated that cisplatin can safely be administered to elderly patients, and arbitrary dose modification or elimination based on age alone is not justified. 2
Renal Function Assessment Is Critical
- Serum creatinine alone is insufficient to evaluate renal function in elderly patients—creatinine clearance must be calculated using Cockcroft-Gault or aMDRD formulas. 1
- Patients with creatinine clearance <50 mL/min should generally not receive cisplatin, though this cutoff is not absolute. 1
- The Cockcroft-Gault formula excludes approximately 20% more patients than other methods, with differences most pronounced in female, elderly, or White patients. 1
- In extremes of obesity, cachexia, and at very high or low creatinine values, direct measurement methods such as 51Cr-EDTA or inulin provide the best GFR estimate. 1
Increased Nephrotoxicity Risk in Elderly
- The incidence of cisplatin-induced nephrotoxicity and acute kidney injury is significantly increased in elderly patients compared to younger patients (9.46% vs 3.37% in one study). 3, 4
- Elderly patients may be more susceptible to nephrotoxicity due to renal hypoperfusion, increased comorbidities (chronic kidney disease, cardiovascular disease, diabetes), and decreased cisplatin clearance. 5, 3
- Renal toxicity is dose-related and cumulative, occurring in 28-36% of patients treated with a single dose of 50 mg/m². 5
- One study found that 85% of elderly patients reached maximum creatinine elevation between chemotherapy initiation and the third course, with renal function beginning to recover thereafter despite continued cisplatin. 6
Risk Factors Requiring Attention
- ACEI/ARB use (OR 3.398) and administration of single high-dose cisplatin applications (OR 2.853) are independent risk factors for cisplatin-induced acute kidney injury in elderly patients. 4
- Coadministration of nephrotoxic drugs such as NSAIDs or COX-2 inhibitors should be avoided or minimized. 1
- Hypertension (OR 2.931) and advanced age (OR 3.433) significantly affect the decline of renal function with cisplatin. 7
- Patients with genitor-urinary tract tumors are at higher risk of renal deterioration. 1
Practical Management Algorithm
Pre-Treatment Assessment
- Calculate creatinine clearance using Cockcroft-Gault formula—do not rely on serum creatinine alone. 1
- Perform geriatric screening assessment to evaluate frailty rather than using age as exclusion criterion. 1
- Review all concurrent medications and discontinue or minimize nephrotoxic agents (NSAIDs, ACEI/ARBs if possible). 1, 3, 4
- Assess for comorbidities: chronic kidney disease, cardiovascular disease, diabetes, hypertension. 3, 7
- Perform baseline audiometric monitoring prior to initiation. 5
Treatment Modifications
- For elderly patients requiring large doses (100 mg/m²), consider using a less nephrotoxic platinum agent instead. 3
- With increasing use of low-dose daily/weekly regimens, routine diuretic treatment is not recommended for elderly patients. 3
- Short duration and low volume hydration may be more suitable for elderly patients considering hemodynamic stability and water balance. 3
- The standard 6-8 hour infusion with intravenous hydration and mannitol should still be used to reduce nephrotoxicity, though toxicity can still occur. 5
Monitoring During Treatment
- Monitor peripheral blood counts weekly and liver function periodically. 5
- Renal function must return to normal before another dose of cisplatin can be given. 5
- Perform neurologic examination regularly to detect peripheral neuropathy. 5
- Continue audiometric monitoring prior to each subsequent dose and for several years post-therapy. 5
- Monitor infusion site closely for possible infiltration during drug administration. 5
Additional Toxicity Concerns in Elderly
Hematologic Toxicity
- Elderly patients experience more severe neutropenia, thrombocytopenia, and leukopenia than younger patients. 5
- Myelosuppression occurs in 25-30% of patients, with nadirs between days 18-23 and recovery by day 39. 5
- Elderly patients may be more susceptible to infectious complications secondary to myelosuppression. 5
Ototoxicity
- Ototoxicity occurs in up to 31% of patients treated with a single 50 mg/m² dose, manifested by tinnitus and/or hearing loss. 5
- The risk increases with prior or simultaneous cranial irradiation, age <5 years, concurrent ototoxic drugs (aminoglycosides, vancomycin), and renal impairment. 5
- Audiometric monitoring should be performed prior to initiation, before each dose, and for several years post-therapy. 5
Common Pitfalls to Avoid
- Do not use serum creatinine alone to assess renal function—this is particularly misleading in elderly patients who may have normal creatinine despite significant renal impairment. 1
- Do not arbitrarily reduce doses or exclude patients based solely on age >70 years—use geriatric assessment tools instead. 1, 2
- Do not continue nephrotoxic comedications (NSAIDs, ACEI/ARBs) during cisplatin therapy. 1, 3, 4
- Do not administer the next cisplatin dose until renal function returns to baseline. 5
- Do not use single high-dose cisplatin applications in elderly patients when fractionated dosing is feasible. 4