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

Abstract

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

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

“…This is in agreement with other studies of similar cohorts showing between 28% and 77% of pathological audiograms (Bissett et al, 1990;Boyer et al, 1990;Stuart et al, 1990;Osanto et al, 1992;Schwabe et al, 1992). After platin-based treatment for other tumour entities, ototoxic changes have been reported in up to 91% of patients (Helson et al, 1978).…”

Functions of epidermal growth factor receptor in cisplatin response of thyroid cells

“…The correlation of hypothyroidism and the cumulative doses of cisplatin implicates this drug in the causation [32]. Furthermore, the molecular mechanism to induce growth arrest and/or apoptosis in the normal thyroid cells is still unknown.…”

Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy

“…9 in patients with testicular cancer who received combinations of cisplatin, bleo mycin, vinblastine, etoposide, and dactinomycin, 4 of 27 indivi duals (15%) developed primary hypothyroid ism. 10 in parti cular, the cumulative doses of cisplatin and vin cristine seem to exacerbate these symptoms. 10 in total, 44% of patients treated with moPP regimen (mechlor ethamine, vin blastine, procarbazine and prednisolone) for Hodgkin disease developed elevated serum thyroid stimulating hormone (tsH) concentrations, although a causative role of iodine load during lymphangiograpy cannot be excluded.…”

“…10 in parti cular, the cumulative doses of cisplatin and vin cristine seem to exacerbate these symptoms. 10 in total, 44% of patients treated with moPP regimen (mechlor ethamine, vin blastine, procarbazine and prednisolone) for Hodgkin disease developed elevated serum thyroid stimulating hormone (tsH) concentrations, although a causative role of iodine load during lymphangiograpy cannot be excluded. 11 Primary hypothyroidism might be caused by cytokine treatments.…”

“…[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] some small molecule tyrosine kinase inhibitors (tKis) have been shown to cause hypothyroidism related symptoms to a variable extent, which can reduce a patient's quality of life. we review the available data for tKi related thyroid dysfunction and the hypothesized patho physiological mechanisms of this toxicity.…”