Journal of the National Cancer Institute Advance Access published online on November 25, 2009
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djp413
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ARTICLE |
Observational Study of Prevalence of Long-term Raynaud-Like Phenomena and Neurological Side Effects in Testicular Cancer Survivors
Affiliations of authors: Department of Oncology, Haukeland University Hospital, Bergen, Norway (MB, OD); Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway (MB, OD); Cancer Clinic, Department of Clinical Cancer Research, Rikshospitalet-Radiumhospitalet Medical Centre, Oslo, Norway (JO, SDF); Institute of Health, Buskerud University College, Drammen, Norway (JO); Department of Oncology, St Olavs University Hospital, Trondheim, Norway (OK); Department of Oncology, University Hospital of North Norway, Tromsø, Norway (RMB); Department of Oncology, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway (RMB); The Cancer Center, Ullevål University Hospital, Oslo, Norway (EAW); Medical Faculty, Faculty Division the Norwegian Radium Hospital, University of Oslo, Oslo, Norway (SDF); Medical Faculty, Faculty Division Ullevål University Hospital, University of Oslo, Oslo, Norway (EAW); Centre for Clinical Research, Research and Development Department, Haukeland University Hospital, Bergen, Norway (TW-L); NKS Olaviken, Hospital for Old Age Psychiatry, Bergen, Norway (ERH)
Correspondence to: Marianne Brydøy, MD, Department of Oncology, Haukeland University Hospital, N-5021 Bergen, Norway (e-mail: marianne.brydoy{at}helse-bergen.no).
Background: Sensory neuropathy (paresthesias), tinnitus, hearing impairment, and Raynaud phenomena are side effects of cisplatin-based chemotherapy used to treat testicular cancer patients. We assessed the long-term occurrence of these side effects among testicular cancer survivors according to the treatment they received.
Methods: A total of 1814 men who were treated for unilateral testicular cancer in Norway during 1980–1994 were invited to participate in a national multicenter follow-up survey conducted during 1998–2002. The men were allocated to six groups according to the treatment they had received. Self-reported symptoms were assessed by a mailed questionnaire that included the Scale for Chemotherapy-Induced Neurotoxicity. A total of 1409 participants who responded to the questionnaire and/or underwent audiometry were assessable in this study. Respondents to the questionnaire (n = 1402) scored the relevant symptoms according to how troubled they were by each (not at all, a little, quite a bit, or very much). Hearing impairment was objectively assessed by audiometry at 4000 Hz in 755 men (seven of whom did not respond to the questionnaire). Group comparisons of symptom assessments were performed with 
2 or Kruskal–Wallis tests. Associations between relevant factors and self-reported symptoms or hearing impairment measured by audiometry were assessed using proportional odds ordinal logistic regression models and linear regression models, respectively. All statistical tests were two-sided.
Results: The median follow-up for the 1409 assessable men was 10.7 years (range = 4–21 years). All chemotherapy groups had statistically significantly higher odds for increasing severity of all assessed symptoms and inferior audiometric results compared with men who did not receive chemotherapy. Among chemotherapy-treated men, 39% (95% confidence interval [CI] = 35% to 43%) reported Raynaud-like phenomena (defined as white or cold hands or fingers [or feet or toes] on cold exposure), 29% (95% CI = 25% to 33%) reported paresthesias in the hands or feet, 21% (95% CI = 18% to 25%) reported hearing impairment, and 22% (95% CI = 19% to 26%) reported tinnitus as major symptoms troubling them quite a bit or very much. Hearing impairment (odds ratio [OR] = 5.3, 95% CI = 3.0 to 9.2) and tinnitus (OR = 7.1, 95% CI = 4.1 to 12.4) were particularly common in the dose-intensive chemotherapy group compared with the no chemotherapy group. Men who were treated with radiotherapy had higher odds of self-reported paresthesias in feet compared with those not treated with radiotherapy (OR = 1.5, 95% CI = 1.01 to 2.1, P = .04).
Conclusion: Long-term survivors of testicular cancer who were treated with cisplatin-based chemotherapy were more often troubled by dose-dependent neurological side effects and Raynaud-like phenomena compared with those who were not treated with chemotherapy.
| CONTEXT AND CAVEATS Prior knowledge The side effects of cisplatin-based chemotherapy used to treat testicular cancer patients include sensory neuropathy, tinnitus, hearing impairment, and Raynaud phenomena. Study design A cross-sectional study that assessed the long-term occurrence of cisplatin-associated side effects among testicular cancer survivors according to the treatment they received. Men who received chemotherapy were allocated to three groups based on cisplatin administration (100 mg/m2 cisplatin over 5 consecutive days in first two groups): up to four cycles, five or more cycles, or dose-intensive chemotherapy (100 mg/m2 cisplatin over 2 consecutive days or a total dose exceeding 100 mg/m2). Self-reported symptoms were assessed by a mailed questionnaire, and hearing impairment was objectively assessed by audiometry at 4000 Hz. Contribution At 4–21 years after the initiation of treatment for testicular cancer, compared with men not treated with chemotherapy, those who had received any chemotherapy had higher risk for increasing severity of all assessed symptoms and, except for those who received five or more cycles, statistically significantly worse audiometric results. Implications These findings support the current approach of using risk-specific recommendations in the treatment of testicular cancer to minimize side effects in good- and intermediate-risk patients and suggest that cisplatin should be administered over the course of 5 days rather than 2 days. Limitations The findings are largely based on self-reported symptoms, and the reported toxic effects were, with the exception of hearing threshold measurements, not objectively confirmed. The screening instrument was brief and did not address each symptom in detail. There was no information about the existence of symptoms before diagnoses or whether they changed over time. From the Editors
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Manuscript received February 16, 2009; revised September 25, 2009; accepted October 13, 2009.
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J Natl Cancer Inst 2009 101: 1659.