RESUMO
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.
Assuntos
Antineoplásicos/efeitos adversos , Sobreviventes de Câncer , Cisplatino/efeitos adversos , Platina/sangue , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Idoso , Cisplatino/farmacocinética , Perda Auditiva/induzido quimicamente , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/mortalidade , Adulto JovemRESUMO
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.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sobreviventes de Câncer , Doenças Cardiovasculares/epidemiologia , Cisplatino/efeitos adversos , Perda Auditiva/induzido quimicamente , Hormônio Luteinizante/sangue , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Neoplasias Testiculares/tratamento farmacológico , Zumbido/induzido quimicamente , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/sangue , Terapia Combinada , Comorbidade , Etoposídeo/administração & dosagem , Seguimentos , Perda Auditiva/epidemiologia , Humanos , Hipogonadismo/epidemiologia , Hipogonadismo/etiologia , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Orquiectomia , Doenças do Sistema Nervoso Periférico/epidemiologia , Inquéritos e Questionários , Neoplasias Testiculares/cirurgia , Zumbido/epidemiologia , Vimblastina/administração & dosagem , Adulto JovemRESUMO
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.