Cisplatin magnesium ototoxicity

BACKGROUND: Platinum compounds are a group of fundamental chemotherapeutics used in the treatment of solid tumors, but they are burdened by side effects, such as ototoxicity. The objective of this study was to evaluate the incidence of ototoxicity caused by platinum compounds and the risk factors affecting its appearance/progression. METHODS: Data from 53 patients who received platinum compounds and who had been off therapy for at least 5 years were analyzed. We collected data relating to audiometry conducted annually from the end of treatment and for at least 5 subsequent years, as well as information concerning the oncological history and comorbidities...

BACKGROUND: Cisplatin (CisPt) has a well-recognized anticancer activity by interacting with DNA and inducing programmed cell death. However, theoretical studies performed on the molecular level suggest that such nonspecific interactions can also take place with many competitive compounds, such as vitamins containing aromatic rings with lone-pair orbitals. It is argued that such direct analogy to interaction of canonical purines can impair the therapeutic effect of Cisplatin. This might be an indicator of reduction of the anticancer therapeutic effects of Cisplatin drug in the presence of vitamins inside the cell nucleus...

OBJECTIVE: The purpose of this study is to evaluate the effect of Mg supplementation on cisplatin ototoxicity in guinea pigs. METHODS: Twenty guinea pigs were divided into two groups and were fed different Mg-containing diets. Following 6 mg/kg of cisplatin injection, the animals were sacrificed and the extent of cochlear damage was assessed with the scanning electron microscope and compared with the control group. Additionally, intracardiac blood samples were taken to determine the plasma Mg levels of the subjects before and after cisplatin exposure...

BACKGROUND: To overcome the ototoxicity of cisplatin, single bolus infusions were replaced by repeated prolonged infusions of lower doses or by continuous infusions at still lower infusion rates. However, considering ototoxicity little is, in fact, known about the tolerance of repeated prolonged or continuous infusion in children. PROCEDURE: Auditory function was monitored along with plasma concentrations of free and total platinum (Pt), and with standard serum parameters (sodium, potassium, calcium, magnesium, phosphate, chloride, and creatinine) in 24 children receiving cisplatin by continuous infusion for the treatment of neuroblastoma and osteosarcoma or by repeated 1 or 6 hr infusions for the treatment of germ cell tumors...

BACKGROUND: In 1998, a prospective multicenter pilot study of the 'Late Effects Surveillance System' (LESS) was started to investigate late effects of patients with Ewing, osteo- or soft-tissue sarcoma. PROCEDURE: Two hundred thirty patients were included in this pilot study. The patients were treated between 1/1/1998 and 6/30/1999 according to the sarcoma protocols COSS-96, CWS-96, and EICESS-92, the median cumulative doses of the focussed drugs were for cisplatin: 360 mg/m(2), for doxorubicin: 270 mg/m(2), and for ifosfamide: 24 g/m(2)...

Outer hair cell (OHC) metabolism is blocked by cisplatin. Concurrent changes in the renal handling of magnesium occur because of the damage cisplatin causes to the renal proximal tubule cells within the thick ascending loop of Henle. Although there is no evidence of cisplatin within the OHCs, there are significant levels of intracellular calcium, the antagonist to magnesium at the cell membrane. The OHC motile response is dependent on intracellular calcium. When the calcium current is suppressed by an antagonist, the extracellular OHC microphonic potential decreases...

Improved survival in testicular cancer has been accompanied by concern about long-term side effects of chemotherapy or radiotherapy. Secondary malignant neoplasia represents one of the worst possible long-term complications, leading to death in patients cured of their primary malignancy. Patients with testicular germ cell tumors appear to have a 2-fold increased risk of developing any second cancer 25-30 years after the diagnosis, resulting in a cumulative incidence of 16-23% at that time. The risk for secondary solid tumors can be mainly attributed to radiotherapy...

Cisplatin is one of the most active cytotoxic agents in the treatment of testicular cancer, but its clinical use is associated with side-effects such as ototoxicity, neurotoxicity and nephrotoxicity. Long-term kidney damage from cisplatin particularly affects the proximal tubular apparatus and can be detected by increased urinary excretion of brush-border enzymes, such as L-alanine-aminopeptidase (AAP), and magnesium. In the current study, the flavonoid silibinin was used as a nephroprotectant for cisplatin-induced nephropathy in a rat animal model...

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...

We have studied the effect on ototoxicity of maintaining serum calcium concentration by calcium gluconate infusion in cancer patients receiving high-dose cisplatin in a randomized study in two groups: 11 patients received calcium gluconate, 4 mg kg-1 i.v. infusion during cisplatin therapy; 11 other patients without any calcium supplementation served as controls. All of them received the first course of chemotherapy, based on cisplatin, 120 mg m2 with a hydration schedule. An audiogram was performed in each patient just before cisplatin and repeated after 1 day and 3 weeks...

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...

PURPOSE: To evaluate the protective effect of low-dose dopamine given as continuous infusion in patients who undergo chemotherapy with the nephrotoxin cisplatin. PATIENTS AND METHODS: Forty-two patients who received high-dose cisplatin-containing chemotherapy entered a prospective, randomized, double-blind, placebo-controlled trial. Twenty-one patients received dopamine, and 21 received placebo. Patients were to receive either infusional dopamine 2 micrograms/kg/min over 48 hours or placebo...

In 19 evaluable cancer patients treated with cis-diamminedichloroplatinum (cis-DDP) Platidiam-Lachema containing chemotherapy the ototoxicity was assessed. There was an increase of hearing threshold of air-conduction in frequency of 6000 and 8000 Hz as compared with pretreatment audiograms in four patients (21%). In one case only the hearing loss was reversible. The usual hearing loss was of 10--15 dB and maximal of 20 dB. In those four patients with ototoxicity the decrease of creatinine clearence under 60 ml/min occurred at the same time...

A study was conducted to determine if cisplatin (CDDP) can be given at higher doses than usual, utilizing aggressive supportive measures. Twelve patients were entered into three dose levels of CDDP: level I, 180 mg/m2 given as a short infusion; level II, 220 mg/m2 also given as a short infusion; level III, 200 mg/m2 divided in five daily doses, each infused over 6 hours. In all cases, CDDP was dissolved and given in 250 ml of a 5% saline solution. For levels I and II, intravenous hydration with 200 to 250 ml/hour D5 1/2NS with potassium and magnesium supplements, was started 24 hours before therapy and continued for 3 to 4 days after, longer if nausea persisted...

Cisplatin has many toxic effects; emesis, impairment of renal function, myelosuppression, peripheral neuropathy, ototoxicity and renal tubular wasting. We used MVP regimen (Mitomycin C, Vp-16, and Cisplatin) in advanced Non-Small Cell Lung Cancer (NSCLC). Using hydration and prophylactic supplementation of sodium and potassium before and during chemotherapy, we have observed the development of hyponatremia in 48 courses (43%), hypokalemia in 23 courses and hypomagnesemia in 11 courses. Some patients showed abnormalities of renal function in 16 courses...

Administration of cis-dichlorodiammineplatinum(II) may be associated with a number of serious side effects, including nephrotoxicity, gastroeintestinal side effects (nausea, vomiting, and diarrhea), myelosuppression, and occasional transient elevations in liver function tests. In addition, ototoxicity (tinnitus and hearing loss), anaphylactic reactions, peripheral neuropathies, and hypomagnesemia with resulting tetany may also be encountered. The toxic potential of this new agent necessitates careful clinical monitoring during treatment...