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C C Berger

Publications and source records attributed to C C Berger.

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Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer.

This study evaluates the degree and relevance of persisting ototoxicity after cisplatin-based standard-dose chemotherapy for testicular cancer, with emphasis on identification of potential factors for an increased risk of this late sequel. Hearing thresholds of 86 patients with a median age of 31 years (range 21-53 years) and a median follow-up time of 58 months (range 15-159 months) were assessed by conventional pure-tone audiometry. Interviews were conducted evaluating the patients' history with special regard to audiological risk factors, as well as circumstances of ototoxic symptoms. Details concerning treatment and patient variables were extracted retrospectively from the patients' charts. An additional screening programme assessed current body functions, blood parameters and other late toxicities. Symptomatic ototoxicity persisted in 20% of patients (59% tinnitus, 18% hearing loss, 23% both), while 10% had experienced completely reversible ototoxic symptoms for a duration of 1-18 months after treatment. Symptoms were bilateral in 81% of patients. Hearing thresholds were compatible with cisplatin-induced hearing loss in 42% of audiograms performed. Subjective (history) and objective (audiogram) findings were not always consistent. The following statistically significant risk factors for ototoxicity were established: high cumulative dose of cisplatin (P < 0.0001); history of noise exposure (P = 0.006). Additionally, high doses of vincristine (P = 0.001) seemed to result in reversible ototoxic symptoms. No other independent risk factors were identified. In conclusion, persisting ototoxicity represents a clinical sequel for approximately 20% of testicular cancer patients treated at standard dose but may affect more than 50% of patients receiving cumulative doses of cisplatin > 400 mg m(-2). Previous noise exposure may also result in a threefold increased risk for cisplatin ototoxicity. Future studies should use these risk factors as important stratification criteria for trials aiming at the evaluation and prevention of cisplatin-induced ototoxicity.

Adult↗

Endocrinological late effects after chemotherapy for testicular cancer.

Type and extent of endocrinological alterations were studied in long-term disease-free survivors after cisplatin-based chemotherapy for testicular cancer. A total of 63 patients with a median age of 30 (19-53) years, and median follow-up of 42 (16-128) months were included. Elevated serum follicle-stimulating hormone (FSH) levels were found in 63% of patients, 24% showed pathologically elevated luteinising hormone (LH) levels with normal and 10% with subnormal testosterone levels. The degree of gonadotropin elevation was highly significantly correlated with the cumulative platinum (P) dose. Patients treated with platinum-vinblastine-bleomycin regimens showed higher gonadotropin levels than those treated with platinum-etoposide-bleomycin. The adrenal androgen dehydroepiandrosterone (DHEA), pathologically elevated in 68% of patients, was significantly correlated with the cumulative doses of chemotherapy (ctx) used and to the gonadotropin levels. Treatment variables, such as type and dose of cytotoxic agents used, as well as degree of gonadotropin elevation were further correlated with changes in oestron, testosterone and 17 alpha-OH-progesterone levels. Cholesterol levels were elevated in 32% of patients and significant interactions between the steroid hormone levels and cardiovascular risk factors could be shown.

17-alpha-Hydroxyprogesterone↗

Evaluation of long-term toxicity after chemotherapy for testicular cancer.

PURPOSE: The current study evaluates the extent and reversibility of late sequelae after chemotherapy in longterm survivors of testicular cancer. The influence of therapy and patient characteristics and the relationship between different toxicities are assessed. PATIENTS AND METHODS: Ninety patients with a median age of 28 years (range, 19 to 53) and a median followup time of 58 months (range, 15 to 159) participated in the clinical examinations, a personal interview, and technical investigations. Overall health and the impact of late toxicity were assessed by the patients. All patients were in complete remission (CR) for at least 1 year. Chemotherapy had consisted of cisplatin (P), bleomycin (B), and vinblastine (V) in 30 patients (33%); P, B, and etoposide (E) in 26 patients (29%); P, B, E, and a vinca alkaloid in 22 patients (24%); and other P-based combination regimens in 12 patients (13%). RESULTS: Alterations of gonadotropin levels (follicle-stimulating hormone [FSH] luteinizing hormone [LH]) in up to 68% of patients and Leydig cell insufficiency in one third of patients were the most frequently detected abnormalities. Approximately 20% of patients had low serum magnesium [Mg] or phosphate levels, or elevated creatinine levels. Cardiovascular risk factors were identified in one third of patients with elevated serum cholesterol levels with or without obesity; 15% had developed arterial hypertension after chemotherapy. The most frequent symptomatic toxicities were Raynaud's phenomenon (RP) in 30% of patients, ototoxicity in 21%, and peripheral neuropathy in 17%. Major risk factors for the development of toxicity were cumulative dose of P (P < .0001 for ototoxicity and neurotoxicity; P < .01 for overall toxicity, gonadal toxicity, and dehydroepiandrosteron elevation; P < .05 for hypertension and Mg depletion) and type of chemotherapy (57% of PVB-treated patients v25% of PEB +/- vincristine-treated patients with RP; P < .01). CONCLUSION: The cumulative dose of P was a major predictor for toxicity. Patients and treatment characteristics such as noise exposure, age, history of smoking, and mode of B application were less important. Further clinical trials should evaluate the sequelae of chemotherapy treatment for testicular cancer prospectively.

Adult↗

Secondary Raynaud's phenomenon and other late vascular complications following chemotherapy for testicular cancer.

182 patients treated with cisplatin-based chemotherapy for testicular cancer at Hannover University Medical School who were in complete remission (CR) for more than 1 year after therapy were randomly selected for the evaluation of late vascular toxicity. 90 patients with a mean age of 28 years (19-53) and a median follow-up of 57.9 months (15-159) participated in this examination. Patients were examined clinically and digital photoelectric pulse plethysmography (PP) and Doppler-flow of the digital arteries after cold exposure were performed. Thirty seven per cent of patients developed symptoms of Raynaud's phenomenon (RP) after chemotherapy, which were transient in 7%. PP proved to be highly diagnostic for RP with a sensitivity of 95% and a specificity of 100%. As significant risk factors for the development of RP, the cumulative dose of bleomycin (P < 0.05) and the use of bleomycin in combination with vinblastine (PVB-regimen) instead of etoposide (PEB-regimen) (P < 0.01) were found. A trend for an increased frequency of RP was observed in patients who received bleomycin as a bolus instead of continuous infusion. No significant correlation was seen with the cumulative or single doses of cisplatin, etoposide or vinblastine, serum magnesium levels during or after chemotherapy or a history of smoking. RP was not associated with the occurrence of neuro- or ototoxicity. All 7 patients with hypertensive blood pressure before chemotherapy developed RP. Furthermore, the median postchemotherapy diastolic blood pressure had increased by 8 mmHg compared to prechemotherapy values, leading to significant hypertension in 8 patients (> 20 mmHg increase). 2 patients developed major vascular events with myocardial infarctions at 4 years and 5 years after chemotherapy, respectively. No cerebral infarction was registered. In summary, RP is the main late vascular toxicity affecting one third of patients after curative chemotherapy for testicular cancer. However, the incidence of RP following PEB-therapy in contrast to PVB-therapy appears to be lower. Major vascular events seem to be rare. The prospective evaluation of late toxicity should be part of current chemotherapy treatment for testicular cancer, and long-term follow-up of surviving patients is recommended.

Adult↗