Overview
This 2026 narrative review from Shantou University Medical College synthesizes pharmacokinetic and long-term toxicity data for the five platinum-based chemotherapeutics in clinical use: cisplatin, carboplatin, nedaplatin, oxaliplatin, and lobaplatin. The review documents long-term residual platinum in serum, urine, and tissues following treatment, characterizes tissue-specific toxicity mechanisms, and surveys mitigation strategies. It also provides population-level context on non-therapeutic dietary platinum exposure: the average adult dietary platinum intake is estimated at 1.44 micrograms per day based on Australian market basket data (Vaughan & Florence 1992, Sydney). The paper is relevant to this wiki as a mechanistic and biomonitoring reference for platinum, not as a food occurrence source.
Key numbers
Non-therapeutic exposure:
- Average dietary platinum intake (Sydney, Australia): 1.44 micrograms per day (Vaughan & Florence 1992); cited as the reference population-level figure for environmental platinum intake
- Each additional noble metal alloy dental restoration associated with approximately 35% increase in urinary platinum (Herr et al. 2003)
Pharmacokinetics summary (Table 1):
- Cisplatin: plasma protein binding greater than 90% (covalent, human serum albumin); alpha half-life 13 min; beta half-life 43 min; gamma half-life 5.4 days; renal excretion 23-50%; low GFR sensitivity
- Carboplatin: protein binding 24-50%; alpha half-life 22 min; beta half-life 116 min; gamma half-life 5.8 days; renal excretion 54-82%; highly GFR-correlated
- Oxaliplatin: 85% protein-bound; three-compartment model; ultrafilterable fraction half-life 24.2 plus or minus 6.9 hours by ICP-MS; renal excretion greater than 50%
- Lobaplatin: low protein binding; total Pt half-life 6.8 plus or minus 4.3 days; ultrafilterable half-life 131 plus or minus 15 min; renal excretion greater than 50%
Long-term residual platinum:
- 20-year follow-up cohort (n=458 testicular cancer survivors): serum platinum significantly elevated versus surgery-only controls even 20 years post-chemotherapy; dose-dependent correlation with cumulative cisplatin dose (Hjelle et al.)
- 45 patients, 8-75 months post-chemotherapy: plasma platinum significantly higher than healthy controls; 24% as ultrafilterable biologically active free form retaining binding activity toward biomacromolecules (Brouwers et al. 2008)
- 34 platinum industry workers: median urinary platinum 1,000-fold higher than unexposed controls; first-phase half-life approximately 50 hours; long-term retention half-life approximately 24 days; workers with high exposure had urinary platinum 25-fold above controls even 2-6 years after cessation (Schierl et al.)
Cisplatin nephrotoxicity:
- 20-30% of patients develop acute kidney injury
- 40-100% experience hypomagnesemia
- Cumulative chronic kidney disease incidence: 37.9% at 3 months post-chemotherapy
- High dose triples CKD risk in 18-year cohort
- Mechanism: OCT2/CTR1 transporter-mediated specific renal accumulation; mitochondrial damage plus oxidative stress; GSH depletion, ROS production; 300-500-fold higher mitochondrial DNA adducts than nuclear DNA; multimodal programmed cell death; renal interstitial fibrosis
Cisplatin ototoxicity:
- Incidence: 75-100%
- Dose-dependent, bilaterally symmetric, progressive, irreversible high-frequency hearing loss
- Greater than 50% have persistent tinnitus
- Each 100 mg/m2 increase in cumulative dose raises hearing impairment risk 5-7%
- Prior noise exposure triples ototoxicity risk
- Mechanism: accumulation in stria vascularis for months to years (retained 18 months); 2-3-fold higher concentration than organ of Corti; destroys blood-labyrinth barrier permeability and endolymphatic K+ homeostasis; CTR1/OCT2 transport; COX17 chaperone involved
Oxaliplatin neurotoxicity:
- 70% sensory neuropathy; 50% chronic type
- Platinum residues in dermal collagen fibers detectable 5-60 months post-withdrawal
- Acute cold-triggered hypersensitivity in approximately 89% at first cycle; mostly resolves spontaneously
- Mechanism: OCT2 accumulation in dorsal root ganglia; Pt ions drive oxidative stress and neuroinflammatory cascade; axonal degeneration and nerve conduction disorder
Carcinogenicity:
- n=5,625 testicular cancer survivors: 1.6-2.1-fold higher second primary neoplasm risk in those receiving 2 or more cycles versus chemo-naive (Hellesnes et al.)
Allergy/hypersensitivity:
- Each 1 mg/L increase in serum platinum linked to 0.007-fold higher allergy risk
- 1 mg/L serum Pt increase in urinary platinum: each additional dental restoration raises urinary Pt sevenfold above pre-implantation level at 3 months post-restoration (Herr et al.)
Relevance to this wiki
This paper provides the mechanistic and long-term biomonitoring context for platinum toxicology on the metals page. The 1.44 micrograms per day dietary intake estimate and the dental restoration-linked urinary platinum data anchor the environmental and low-level occupational exposure discussion. The therapeutic toxicology (cisplatin nephrotoxicity, ototoxicity, oxaliplatin neurotoxicity) is specific to pharmacological doses and provides the mechanistic basis for understanding why platinum group elements are toxicologically significant, while the food occurrence data remain distinct from therapeutic exposure routes. No food occurrence data are contributed by this review.
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