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Platinum exposure and cause‐specific mortality among patients with testicular cancer

2019; Wiley; Volume: 126; Issue: 3 Linguagem: Inglês

10.1002/cncr.32538

1097-0142

Harmke J. Groot, Flora E. van Leeuwen, Sjoukje Lubberts, Simon Horenblas, Ronald de Wit, J. Alfred Witjes, Gerard Groenewegen, Philip Poortmans, Maarten C.C.M. Hulshof, Otto W.M. Meijer, Igle J. de Jong, Hetty A. van den Berg, Tineke J. Smilde, Ben Vanneste, Maureen J.B. Aarts, Katarzyna Jóźwiak, Alexandra W. van den Belt‐Dusebout, Jourik A. Gietema, Michael Schaapveld,

Cholangiocarcinoma and Gallbladder Cancer Studies

Background Although testicular cancer (TC) treatment has been associated with severe late morbidities, including second malignant neoplasms (SMNs) and ischemic heart disease (IHD), cause‐specific excess mortality has been rarely studied among patients treated in the platinum era. Methods In a large, multicenter cohort including 6042 patients with TC treated between 1976 and 2006, cause‐specific mortality was compared with general population mortality rates. Associations with treatment were assessed with proportional hazards analysis. Results With a median follow‐up of 17.6 years, 800 patients died; 40.3% of these patients died because of TC. The cumulative mortality was 9.6% (95% confidence interval [CI], 8.5%‐10.7%) 25 years after TC treatment. In comparison with general population mortality rates, patients with nonseminoma experienced 2.0 to 11.6 times elevated mortality from lung, stomach, pancreatic, rectal, and kidney cancers, soft‐tissue sarcomas, and leukemia; 1.9‐fold increased mortality (95% CI, 1.3‐2.8) from IHD; and 3.9‐fold increased mortality (95% CI, 1.5‐8.4) from pneumonia. Seminoma patients experienced 2.5 to 4.6 times increased mortality from stomach, pancreatic, bladder cancer and leukemia. Radiotherapy and chemotherapy were associated with 2.1 (95% CI, 1.8‐2.5) and 2.5 times higher SMN mortality (95% CI, 2.0‐3.1), respectively, in comparison with the general population. In a multivariable analysis, patients treated with platinum‐containing chemotherapy had a 2.5‐fold increased hazard ratio (HR; 95% CI, 1.8‐3.5) for SMN mortality in comparison with patients without platinum‐containing chemotherapy. The HR for SMN mortality increased 0.29 (95% CI, 0.19‐0.39) per 100 mg/m 2 platinum dose administered ( P trend < .001). IHD mortality was increased 2.1‐fold (95% CI, 1.5‐4.2) after platinum‐containing chemotherapy in comparison with patients without platinum exposure. Conclusions Platinum‐containing chemotherapy is associated with a dose‐dependent increase in the risk of SMN mortality.