Observational Study of Prevalence of Long-term Raynaud-Like Phenomena and Neurological Side Effects in Testicular Cancer Survivors

Abstract

BackgroundSensory 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.MethodsA 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 χ2 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.ResultsThe 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).ConclusionLong-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.

Multi-Institutional Assessment of Adverse Health Outcomes Among North American Testicular Cancer Survivors After Modern Cisplatin-Based Chemotherapy

“…47 Raynaud phenomenon is a known toxicity of bleomycin 39 and may be associated with cisplatin. 38 Although we found no association with cumulative cisplatin dose and Raynaud phenomenon, risk was significantly elevated by 1.3-fold per 90,000-IU increase in bleomycin dose, a finding consistent in part with Glendenning et al, 39 who evaluated risk in 180,000-IU increments (OR, 2.9 per 180,000-IU increase; P , .001).…”

“…The significant association between cumulative cisplatin dose and the number of cisplatin-related AHOs extends existing evidence that cisplatin contributes to the development of peripheral neuropathy 38,39 and ototoxicity, 18,37,38 with dose-dependent relationships noted previously for each individually.…”

“…10,11,[37][38][39] Of four small US-based investigations, [40][41][42][43] a limited number of AHOs was addressed in one series (143 patients) 41 but also included treatments with carboplatin-based and other non-cisplatin-based regimens and excluded established cisplatin complications (eg, neuropathy).…”

The Sound of Silence: A Proxy for Platinum Toxicity

“…4,5 Although the report by Frisina et al 1 is a valuable contribution to the literature, it would have benefitted from inclusion of additional information, such as pretreatment assessments, the impact of ototoxicity on health-related QoL, details about and adjustment for other ototoxic agents (eg, aminoglycosides), and occupational hearing loss after completion of cisplatin-based chemotherapy. The cohort represents TC survivors receiving standard cisplatin-based chemotherapy for metastatic disease for which we do have some long-term ototoxicity outcomes, 6 whereas high-quality data on ototoxicity after adjuvant chemotherapy with either one or two cycles of bleomycin, etoposide, and cisplatin (BEP) or carboplatin as well as after high-dose chemotherapy are still lacking.…”

“…22,23 Pooling long-term toxicity data after three cycles of BEP and four cycles of EP for a metaanalysis of these outcomes might be worthwhile, especially because we have learned that extrapolation of acute toxicities is not always correct in the long term: less long-term neuropathy after chemotherapy with vinblastine as opposed to etoposide in combination with cisplatin and bleomycin was surprising, because vinblastine causes substantially more short-term paresthesia than etoposide. 6,24 Thereby, phase IV studies could help decision making in the absence of level I evidence.…”