Review Article

Toxicities Associated with Cisplatin-Based Chemotherapy and Radiotherapy in Long-Term Testicular Cancer Survivors

Table 3

Numbers and types of self-reported adverse health outcomes among 952 cisplatin-treated germ cell tumor survivors in North America.

Adverse health outcomes (AHOs)Total patients (N = 952) N (%)Treatment regimen
EP (4 cycles) (N = 294) N (%)BEP (3 cycles) (N = 364) N (%)BEP (4 cycles) (N = 170) N (%)

Total number of AHOs
Median (range)2 (0–11)2 (0–9)2 (0–11)2 (0–10)
0194 (20.4)64 (21.8)83 (22.8)25 (14.7)
1209 (21.9)68 (23.1)71 (19.5)42 (24.7)
2191 (20.1)61 (20.8)82 (22.5)27 (15.9)
3143 (15.0)48 (16.3)48 (13.2)25 (14.7)
496 (10.1)28 (9.5)38 (10.4)18 (10.6)
5 or more119 (12.5)25 (8.5)42 (11.5)33 (19.4)
Type of AHOs
Yes353 (37.1)104 (35.4)130 (35.7)65 (38.2)
No599 (62.9)190 (64.6)234 (64.3)105 (61.8)
Hearing impairment§
Yes300 (31.5)95 (32.3)109 (30.0)56 (33.0)
No652 (68.5)199 (67.7)255 (70.0)114 (67.0)
Peripheral neuropathyǁ
Yes257 (27.0)86 (29.2)78 (21.4)54 (31.8)
No695 (73.0)208 (70.8)286 (78.6)116 (68.2)
Peripheral neuropathy plus tinnitus and/or hearing issue
Yes156 (16.4)49 (16.7)48 (13.2)31 (18.2)
No796 (83.6)245 (83.3)316 (86.8)139 (81.8)
Hypertension and on prescription medication
Yes110 (11.6)35 (11.9)45 (12.4)15 (8.8)
No842 (88.4)259 (88.1)319 (87.6)155 (91.2)
Hypercholesterolemia and on prescription medication
Yes100 (10.5)32 (10.9)31 (8.5)20 (11.8)
No852 (89.5)262 (89.1)333 (91.5)150 (88.2)
Cardiovascular disease††
Yes14 (1.5)4 (1.4)4 (1.1)2 (1.2)
No‡‡938 (98.5)290 (98.6)360 (98.9)168 (98.8)
Raynaud phenomenon
Yes178 (18.7)34 (11.6)78 (21.4)49 (28.8)
No§§774 (81.3)260 (88.4)286 (78.6)121 (71.2)
Peripheral vascular disease
Yes29 (3.0)5 (1.7)8 (2.2)10 (5.9)
Noǁǁ923 (97.0)289 (98.3)356 (97.8)160 (94.1)
Thromboembolic disease¶¶
Yes5 (0.5)004 (2.4)
No947 (99.5)294 (100)364 (100)166 (97.6)
Renal disease
Yes25 (2.6)7 (2.4)6 (1.6)7 (4.1)
No927 (97.4)287 (97.6)358 (98.4)163 (95.9)
Diabetes and on prescription medication†††
Yes30 (3.1)9 (3.1)10 (2.7)3 (1.8)
No922 (96.9)285 (96.9)354 (97.3)167 (98.2)
Benign thyroid disease
Yes23 (2.4)6 (2.0)9 (2.5)5 (2.9)
No‡‡‡929 (97.6)288 (98.0)355 (97.5)165 (97.1)
Problems with balance/vertigo/dizziness§§§
Yes89 (9.3)26 (8.8)37 (10.2)16 (9.4)
No863 (90.7)268 (91.2)327 (89.8)154 (90.6)
Hypogonadism with testosterone therapyǁǁǁ
Yes93 (9.9)25 (8.6)37 (10.3)16 (9.5)
No851 (90.1)267 (91.4)323 (89.7)152 (90.5)
Erectile dysfunction
Yes115 (12.1)28 (9.5)39 (10.7)34 (20.0)
No¶¶¶837 (87.9)266 (90.5)325 (89.3)136 (80.0)
Psychotropic prescription medication for anxiety and/or depression
Yes99 (10.4)34 (11.6)27 (7.4)20 (11.8)
No853 (89.6)260 (88.4)337 (92.6)150 (88.2)

Adapted with permission from Fung et al. [40] (Table 3). BEP: bleomycin, etoposide, cisplatin; CAD: coronary artery disease; EP: etoposide, cisplatin; MI: myocardial infarction. values are derived from the chi-square test comparing the proportions of AHOs reported by TCS in the EPX4 and BEPX3 treatment groups. Except for Raynaud phenomenon () and peripheral neuropathy (), the values for all other AHOs were >0.05; category includes 3 participants for whom this outcome was not stated; among all 952 participants, 270 (28.4%) reported problems hearing words, sounds, or language in crowds, 13 (1.4%) required hearing aid, and 2 (0.2%) had complete deafness (questions derived from the hearing handicap inventory by Ventry and Weinstein) [166]; 109 (11.4%) had “quite a bit” or “very much” difficulty hearing and 75 (7.9%) had “quite a bit” or “very much” reduced hearing (EORTC-CIPN20 and SCIN) ([167, 168]). Category includes 48 participants for whom this outcome was not stated; among all 952 participants, the number of patients reporting “quite a bit” or “very much” to the following questions are as follows: 123 (12.9%) tingling fingers or hands, 167 (17.5%) tingling toes or feet, 121 (12.7%) numbness in fingers or hands, 161 (16.9%) numbness in toes or feet, 34 (3.6%) shooting/burning pain in fingers or hands, 70 (7.4%) shooting/burning pain in toes or feet (EORTC-CIPN20) [167]; 134 (14.1%) pain and tingling in toes or feet, and 86 (9.0%) pain and tingling in hands or fingers (SCIN) [168]. Category includes 16 participants for whom this outcome was not stated; category includes 11 participants for whom this outcome was not stated; category includes 3 participants for whom this outcome was not stated; ††includes coronary artery disease, heart failure, and cerebrovascular disease (categories not mutually exclusive, and each category was counted as one AHO). Among all participants, 7 (0.7%) reported coronary artery disease (3 occurrences for coronary artery disease, 5 occurrences of angioplasty or stent, and 5 occurrences of heart attack or myocardial infarction); 1 patient reported heart failure; and 10 (1.0%) reported cerebrovascular disease (6 occurrences of transient ischemic attacks, 4 occurrences of stroke, and 1 occurrence of carotid artery surgery); ‡‡category includes 21 participants for whom this outcome was not stated; §§category includes 12 participants for whom this outcome was not stated; ǁǁcategory includes 19 participants for whom this outcome was not stated; ¶¶deep vein thrombosis (DVT) and pulmonary embolism (PE) developed simultaneously in 3 participants and was counted as one thromboembolic event for each. The remaining 2 participants reported DVT only. Category includes 19 participants for whom this outcome was not stated; category includes 26 participants for whom this outcome was not stated; †††among all participants, 13 (1.4%) and 22 (2.3%) reported use of insulin and oral antiglycemic agents, respectively (categories not mutually exclusive). Category includes 15 participants for whom this outcome was not stated; ‡‡‡category includes 19 participants for whom this outcome was not stated; §§§of the 89 patients, 47 reported persistent dizziness or vertigo and 63 reported symptoms of dizziness when standing up (categories not mutually exclusive). Category includes 40 participants for whom this outcome was not stated; ǁǁǁeight participants who underwent bilateral orchiectomy were excluded from this category; ¶¶¶category include 7 participants for whom this outcome was not stated; participants could report more than one psychotropic medication. Psychotropic medications used by the 99 participants include aripirazole (n =2), alprazolam (n = 5), amphetamine-dextroamphetamine (n = 9), bupropion (n = 10), buspirone (n = 1), citalopram (n = 6), clonazepam (n = 8), desvenlafaxine (n = 1), diazepam (n = 1), duloxetine (n = 7), escitalopram (n = 16), fluvoxamine (n = 1), fluoxetine (n = 4), hydroxyzine (n = 1), lisdexamfetamine (n = 4), lorazepam (n = 6), methylphenidate (n = 5), nortriptyline (n = 2), olanzapine (n = 2), paroxetine (n = 7), trazodone (n = 5), sertraline (n = 11), and venlafaxine (n = 7).