Long-term serum platinum changes and their association with cisplatin-related late effects in testicular cancer survivors.

BACKGROUND: The long-term toxicities after cisplatin-based chemotherapy (CBCT) reveal a remarkable inter-individual variation among testicular cancer survivors (TCSs). Therefore, we assessed long-term platinum (Pt) changes and their associations with CBCT-related late effects in TCSs. MATERIAL AND METHODS: In 77 TCSs treated with CBCT from 1984 to 1990, blood samples for analyses of Pt and a questionnaire including self-reported neuro- and ototoxicity (NTX) symptoms were collected during two follow-up surveys at median 12 (Survey I; SI) and 20 (Survey II; SII) years after treatment. Information about second cancers after SII was retrieved from the Norwegian Cancer Registry. RESULTS: A larger Pt decline from SI to SII was associated with a decreased risk of a second cancer diagnosis (HR 0.78, 95% CI 0.62-0.99 per 10 ng/L/year), and worsening of paresthesias in hands (OR 1.98, 95% CI 1.09-3.59 per 10 ng/L/year) and tinnitus (OR 1.51, 95% CI 1.01-2.27 per 10 ng/L/year). CONCLUSION: In summary, we found a significant association between a larger Pt decline and a reduced risk of second cancers and deterioration of paresthesias in hands and tinnitus.

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

OBJECTIVE: To evaluate the associations between long-term serum levels of platinum (se-Pt) and neurotoxicity and ototoxicity (NTX), endocrine gonadal function (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.

Long-term platinum retention after platinum-based chemotherapy in testicular cancer survivors: a 20-year follow-up study.

AIM: Evaluation of long-term platinum (Pt) retention in testicular cancer survivors (TCSs) treated with platinum-based chemotherapy to elucidate possible mechanisms of developing late effects. PATIENTS AND METHODS: 458 TCSs treated 1980-1994 participated in a national follow-up study (2007-2008). Four treatment groups were evaluated for long-term serum Pt levels: surgery (n=135), cumulative cisplatin≤850 mg (n=252), cisplatin>850 mg (n=57) and carboplatin (n=14). RESULTS: The median observation time was 20 (range=13-28) years. The median Pt level according to treatment group was: surgery, 50 ng/l; cisplatin≤850 mg, 85 ng/l; cisplatin>850 mg, 106 ng/l; carboplatin, 40 ng/l. The risk for having a Pt level in the highest quartile was positively associated with cisplatin dose (Ordinal regression (OR)=1.29, per 100 mg increase in cisplatin dose, 95% Confidence interval (CI)=1.20-1.38), and negatively associated with follow-up time (OR=0.50 per 5-year increase in follow-up time, 95% CI=0.37-0.68). CONCLUSION: Pt levels are significantly elevated in serum at a median of 20 years after cisplatin-based chemotherapy for testicular cancer.