Associations between long-term serum platinum and neurotoxicity and ototoxicity, endocrine gonadal function, and cardiovascular disease in testicular cancer survivors

作者：Hjelle Line V; Bremnes Roy M; Gundersenc Per O M; Sprauten Mette; Brydoy Marianne; Tandstad Torgrim; Wilsgaard Tom; Fossa Sophie D; Oldenburg Jan; Haugnes Hege S

来源：Urologic Oncology-Seminars and Original Investigations, 2016, 34(11): 487.e13-487.e20.

DOI：10.1016/j.urolonc.2016.06.012

• Testicular cancer
• Long-term follow-up
• Cisplatin retention

Objective: To evaluate the associations between long-term serum levels of platinum (se-Pt) and neurotoxicity and ototoxicity (NTX), endocrine gonadal endocrine-GF), and cardiovascular disease (CVD) in testicular cancer survivors.
Material and methods: A total of 292 cisplatin-treated testicular cancer survivors (1980-1994) participated in a national follow-up study (2007-2008). Se-Pt was quantified by inductively coupled plasma mass spectrometry, and categorized in quartiles. Symptoms of NTX were assessed with scale for chemotherapy-induced neurotoxicity (SCIN), with each symptom in 4 categories and total SCIN score categorized in quartiles. Endocrine-GF was categorized according to cutoff values for the 25, 50, and 75 percentiles of luteinizing hormone (LH) and testosterone within each decadal age group established from a control group. CVD was defined as ischemic heart disease, stroke, or artery occlusion. Associations between se-Pt levels and NTX, endocrine-GF, or risk for CVD, were analyzed with ordinal logistic regression and Cox regression, respectively.
Results: Median follow-up was 19 years (range: 13-28). In ordinal regression analyses, increasing quartiles of se-Pt were significantly associated with increasing quartiles of SCIN (P for trend = 0.05), increased tinnitus (P<0.001), and increased hearing impairment (P = 0.04). The association remained significant for tinnitus when adjusting for cisplatin dose. Increasing LH quartiles was associated with increasing se-Pt quartiles (P = 0.04). No association between se-Pt in quartiles and CVD was established.
Conclusion: Median 19 years after treatment, increasing quartiles of se-Pt are associated with increasing SCIN score, tinnitus, hearing impairment, and increasing LH levels. However, these associations remained significant only for tinnitus and LH when adjusting for administered cisplatin dose.

• 出版日期2016-11