Gonadal dysfunction in patients treated for metastatic germ-cell tumors.

Summary Twenty-seven patients cured of advanced testicular cancer by cisplatin-based chemotherapy have been assessed, a median of 30 months after start of treatment, for the long-term effects of such treatment on renal, endocrine, audiometric, reproductive and respiratory function. To control for the effects of orchidectomy on endocrine function a similar group of 11 patients cured by orchidectomy alone was also assessed. The extents of impairment in hearing and renal function were related to the total dose of cisplatin received, while the majority of patients had respiratory impairment which was, in part, related to the total dose of bleomycin. TSH was significantly higher in the chemotherapy group although serum free thyroxine and free T3 were normal in all. FSH was raised in 67% of the chemotherapy group and in 45% of the orchidectomy group while LH was raised in 75% and 45% respectively. Serum testosterone was normal in all. MethodsClinical notes were reviewed to obtain details of investigations at presentation and of chemotherapy received. Hepatic and renal function, serum TSH, free thyroxine and free T3, serum FSH, LH and testosterone, tumour markers (afetoprotein and P-human chorionic gonadotrophin) and full blood count were measured. Standard laboratory normal ranges were used and serum hormones were measured by specific immunometric methods.Pulmonary function assessment comprised measurement of vital capacity (VC), forced residual capacity (FRC), residual volume (RV), total lung capacity (TLC), forced expiratory capacity in one second (FEV,), peak expiratory flow rate (PFR), transfer factor coefficient (KCO), total lung transfer factor (TLCO), total alveolar volume (TAV) and effective alveolar volume (EAV). TLCO was measured by single breath-hold method with correction for haemoglobin concentration, EAV by single breath helium dilution and lung volumes by steady state helium dilution. Values other than TAV and EAV were expressed as standardised residuals (Miller & Pincock, 1988) with expected values determined from height and age by published regression equations (European Coal and Steel Community Recommendations, 1983

Section: Thyroidfunctionsupporting

confidence: 72%

Long-term toxicity of chemotherapy for testicular cancer – the cost of cure

Stuart

Woodroffe²,

Grundy³

et al. 1990

“…It has been postulated that male patients over 25 years of age treated with ctx may be more susceptible to persisting gonadal impairment than younger patients (Horwich et al, 1995;Leitner et al, 1986). A toxicity-age correlation could be seen for FSH levels in our patients and statistically significant differences of LH and FSH elevations were found in patients <28 vs ) 28 years after treatment when lowtoxicity regimens were considered.…”

Section: Materials and Methods Patientsmentioning

confidence: 44%

“…Although normalisation of elevated LH levels with the time of follow-up has been suggested (Leitner et al, 1986), a relevant decrease in LH and FSH level elevation was seen only in the subset of our patients who had received rather toxic high-dose platinum-based regimens resulting in initially very high gonadotropin levels. In all other treatment groups long-term median LH and FSH elevations persisted or even slightly increased as compared with levels of patients with short observation periods.…”

Section: Materials and Methods Patientsmentioning

confidence: 50%

“…Yet, data on endocrine toxicity in patients with testicular tumours have mainly focused on fertility issues, and only a few investigations were concerned with additional longterm endocrinological abnormalities of hormone metabolism. Besides sporadically documented minor thyroid-stimulating hormone elevations (Bosl and Bajorunas, 1987;Gietema et al, 1992;Leitner et al, 1986;Schwabe et al, 1992), alterations in oestradiol levels have been found in patients treated for testicular cancer (Gietema et al, 1992;Schwabe et al, 1992), but the impact of these findings, e.g. on lipid profiles and further metabolic changes, were not investigated.…”

Section: Materials and Methods Patientsmentioning

confidence: 99%

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Endocrinological late effects after chemotherapy for testicular cancer

Berger

Bokemeyer²,

Schuppert³

et al. 1996

Summary 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 platinumvinblastine -bleomycin regimens showed higher gonadotropin levels than those treated with platinumetoposide-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 17a-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.

“…Commonly recognised are chronic renal impairment (Bosl et al, 1986;Meijer et al, 1983;Vogelzang et al, 1985), Raynaud's phenomenon (Vogelzang et al, 1981), peripheral neuropathy (Thompson et al, 1984), high frequency hearing loss and tinnitus (Vermorken et al, 1983) and infertility (Drasga et al, 1983). The implication of chemotherapy in major vascular occlusions (Samuels et al, 1987), second malignancy and hypertension is less clearly defined.…”

mentioning

confidence: 99%

Long-term sequelae of treatment for testicular germ cell tumours

Bissett

Kunkeler²,

Zwanenburg³

et al. 1990

Summary Seventy-four patients previously treated in our department for germ cell tumour of the testis underwent a series of tests to determine the frequency of long-term therapeutic complications. All had received cisplatin-based chemotherapy as part of their treatment. There was a significant deterioration in renal function throughout the group. Eighteen (24%) had supine blood pressure greater than systolic 140 mmHg or diastolic 90 mmHg after treatment but hypertension did not correlate with renal impairment. Raynaud's phenomenon was common after chemotherapy (26/74) as was persistent sensory neuropathy (23/74). Although 34% had testosterone levels below the normal range, only six patients had a low free testosterone index with one testis still in situ; 18 patients have fathered children after chemotherapy. Approximately half of the patients completed a psychosexual questionnaire and some 30% of them admitted to sexual problems which they attributed to their treatment. Long-term sequelae of cisplatin-based chemotherapy for testicular malignancy are frequent and persistent, and follow-up of these patients should include prospective measurement of changes in blood pressure.