Clinical and Genome-Wide Analysis of Serum Platinum Levels after Cisplatin-Based Chemotherapy

Clin Cancer Res. 2019 Oct 1;25(19):5913-5924. doi: 10.1158/1078-0432.CCR-19-0113. Epub 2019 Jul 11.


Purpose: Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1-35 years after CBC and evaluate genetic contributions to these levels.

Experimental design: Eligible TCS given 300 or 400 (±15) mg/m2 cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires, and had crude serum platinum levels measured. Associations between serum platinum and various risk factors and toxicities were assessed after fitting a biexponential model adjusted for follow-up time and cumulative cisplatin dose. A genome-wide association study (GWAS) was performed using the serum platinum residuals of the dose and time-adjusted model.

Results: Serum platinum levels exceeded the reference range for approximately 31 years, with a strong inverse relationship with creatinine clearance at follow-up (age-adjusted P = 2.13 × 10-3). We observed a significant, positive association between residual platinum values and luteinizing hormone (age-adjusted P = 6.58 × 10-3). Patients with high residual platinum levels experienced greater Raynaud phenomenon than those with medium or low levels (age-adjusted ORhigh/low = 1.46; P = 0.04), as well as a higher likelihood of developing tinnitus (age-adjusted ORhigh/low = 1.68, P = 0.07). GWAS identified one single-nucleotide polymorphism (SNP) meeting genome-wide significance, rs1377817 (P = 4.6 × 10-8, a SNP intronic to MYH14).

Conclusions: This study indicates that residual platinum values are correlated with several cisplatin-related toxicities. One genetic variant is associated with these levels.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / blood*
  • Antineoplastic Agents / therapeutic use
  • Cancer Survivors
  • Cisplatin / blood*
  • Cisplatin / therapeutic use
  • Follow-Up Studies
  • Genome-Wide Association Study / methods
  • Humans
  • Male
  • Middle Aged
  • Myosin Heavy Chains / genetics
  • Myosin Type II / genetics
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Testicular Neoplasms / blood*
  • Testicular Neoplasms / drug therapy
  • Testicular Neoplasms / genetics*
  • Testicular Neoplasms / pathology
  • Young Adult


  • Antineoplastic Agents
  • MYH14 protein, human
  • Myosin Type II
  • Myosin Heavy Chains
  • Cisplatin