Impact of Long-Term Serum Platinum Concentrations on Neuro- and Ototoxicity in Cisplatin-Treated Survivors of Testicular Cancer

Abstract

A B S T R A C T PurposeCisplatin-induced neurotoxicity and ototoxicity (NTX) are important adverse effects after chemotherapy for testicular cancer (TC). Although serum platinum is measurable years after therapy, its impact on NTX has not been evaluated. Patients and MethodsIn all, 169 cisplatin-treated survivors of TC provided blood samples at Survey I and reported NTX during Survey I (1998Survey I ( -2002 and Survey II (2007. Serum platinum was quantified by inductively coupled plasma mass spectrometry. Patient-reported outcomes were evaluated with the Scale for Chemotherapy-Induced Neurotoxicity (SCIN), regarding the extent of symptom bother as 0, "not at all"; 1, "a little"; 2, "quite a bit"; or 3, "very much." Summing the six symptom scores yielded a total SCIN score of 0 to 18. Categorizing total SCIN scores into quartiles yielded similar-sized groups with increasing symptoms. Multivariate ordinal logistic regression analyses evaluated associations between NTX and long-term serum platinum levels, adjusting for cisplatin dose, dosing schedule, and age. ResultsAt Survey I, a significant four-to five-fold association with total SCIN score emerged for the highest serum platinum quartile (odds ratio [OR], 4.69; 95% CI, 1.82 to 12.08). Paresthesias and Raynaud's syndrome (hands and feet) showed significant two-to four-fold increased risks with the highest platinum quartile. At Survey II, total SCIN score remained significantly associated with the highest platinum quartile (OR, 4.28; 95% CI, 1.36 to 13.48). Paresthesias (hands and feet) and tinnitus showed significant three-to four-fold increased risks for the highest platinum quartile. Cumulative cisplatin dose was not associated with total SCIN score or individual SCIN symptoms in multivariate analyses. ConclusionHere we document a significant relationship between increasing levels of residual serum platinum and NTX severity after adjusting for initial cisplatin dose.

Comprehensive identification of genes driven by ERV9-LTRs reveals TNFRSF10B as a re-activatable mediator of testicular cancer cell death

“…61 Nevertheless, 20% of patients with metastatic disease cannot be cured, 62 and cDDP displays severe toxicities, for example, neurotoxicity. [37][38][39] This work indicates that HDACi and cDDP synergistically induce cell death in several testicular cancer-derived cell lines (GH, Susa, 1618-K). This raises the perspective of clinically using HDACis on testicular cancers that do not respond sufficiently to current standard therapeutic regimens.…”

Residual Platinum Concentrations in Post-Cancer Chemotherapy and Healthy Control Populations Using an Automated, 96-Well Plate Method and Inductively Coupled Plasma Mass Spectrometry

“…Both studies documented a significant relationship between increasing concentrations of residual serum Pt and the severity of neurotoxicity in testicular cancer survivors treated with cisplatin-based chemotherapy, even when analyses were adjusted for initial cumulative cisplatin dose (3,4). The long-term persistence of increased serum Pt concentrations has been known for several decades, with investigations documenting amounts up to 1000-fold greater than in unexposed controls (2,5,16,17).…”

“…Although it is well established that a cumulative dose of platinum administered intravenously is associated with a number of these adverse effects, it is also recognized that in European populations, platinum concentrations remain significantly increased in serum years after chemotherapy completion (2)(3)(4). Moreover, Brouwers et al (5) showed that these circulating platinating agents remain partly reactive.…”

Patient-Reported Measures of Hearing Loss and Tinnitus in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review

“…It has educational, vocational, and social consequences that may vary by age of onset (Bertolini et al, 2004;Brock et al, 2012;Langer, am Zehnhoff-Dinnesen, Radtke, Meitert, & Zolk, 2013;Travis et al, 2014). Tinnitus, which may interfere with sleep, daily function, and quality of life (Sprauten et al, 2012), is another important hearing outcome that is common following platinum chemotherapy.…”