Cisplatin is one of the most widely used antineoplastic agents in the treatment of solid tumour and haematological malignancies, including cancers of the testes, ovary, bladder, head and neck, oesophagus, stomach and lung, as well as lymphoma and osteosarcoma. Its non-specific targeting commonly results in adverse effects and toxicities affecting the gastrointestinal, renal, neurological and haematological systems even when administered at standard doses. Since cisplatin-related toxicities are dose-dependent, these may be more pronounced in the setting of a cisplatin overdose, resulting in significant morbidity and/or mortality. The incidence of cisplatin overdoses is unknown; however, early-phase clinical trials utilizing high-dose cisplatin, and case reports in the overdose setting have characterized the clinical features associated with cisplatin overdoses, highlighting some therapeutic strategies for consideration. To date, no published guidelines exist for managing a cisplatin overdose. The major toxicities of a cisplatin overdose include nausea and vomiting, renal insufficiency, electrolyte abnormalities, myelosuppression, ototoxicity, peripheral neuropathy, hepatotoxicity and retinopathy. Diarrhoea, pancreatitis, seizures and respiratory failure have also been reported. No specific antidote for cisplatin exists. Key management principles and strategies to lessen toxicities include renoprotection and enhancing drug elimination with aggressive intravenous hydration with or without the use of an osmotic diuretic, and avoidance of nephrotoxic medications. Sodium thiosulfate and plasmapheresis, with or without haemodialysis support, should be strongly considered. Close monitoring of clinical and laboratory parameters, and institution of supportive therapies, including antiemetics and haematopoietic colony stimulating factor support, are warranted. Based on the current literature, experimental therapies such as amifostine, ditiocarb sodium (diethyldithiocarbamate), acetylcysteine, fosfomycin and colestipol are of limited clinical effectiveness and remain investigational. This review serves to highlight the clinical spectrum of toxicities resulting from a cisplatin overdose, to critically appraise the available literature and to present a suggested algorithmic approach for the initial management of a cisplatin overdose.

Cisplatin overdose: toxicities and management.

PURPOSE: To evaluate the risk of major thromboembolic complications in male germ cell cancer patients receiving cisplatin-based chemotherapy and to review the literature on this subject. PATIENTS AND METHODS: One hundred seventy-nine germ cell cancer patients treated between January 1979 and May 1997 in our hospital were analyzed with respect to risk factors for developing thromboembolic events, such as baseline tumor characteristics, prior tumor therapy, administration of cytostatic agents, and the use of antiemetic drugs. The patients were treated with a variety of combination chemotherapy regimens, primarily cisplatin-containing combination regimens. RESULTS: Of the 179 patients, 15 patients (8.4%) were identified who developed a total of 18 major thromboembolic complications in the time period between the start of chemotherapy and 6 weeks after administration of the last cytostatic drug in first-line treatment. Of these 18 events, three (16.7%) were arterial events, including two cerebral ischemic str...

Thromboembolic Events During Chemotherapy for Germ Cell Cancer: A Cohort Study and Review of the Literature

Neurotoxicity secondary to antineoplastic drugs.

The platinum agents (cisplatin, carboplatin and oxaliplatin) are among the most useful anticancer agents available to oncologists. The drugs have the potential to produce both mild and more serious side effects. However, in general, the platinum agents can be delivered with acceptable toxicity, even when used in combination chemotherapy regimens. Furthermore, with appropriate dose modifications, the large majority of patients who may benefit from this class of cytotoxic pharmaceutical drugs will be able to complete a planned therapeutic programme.

Toxicities of the platinum antineoplastic agents

The double-edged sword: Neurotoxicity of chemotherapy

Cis-Platinum is a phase II chemotherapeutic agent effective against a variety of tumors. Known toxic effects include gastrointestinal, renal, audiologic, and hematologic as well as idiosyncratic and atopic. A 30-year-old male who was treated with cis-Platinum diamminedichloride II for disseminated embryonal cell carcinoma of the testicle developed seizures and cortical blindness.

Seizures and transient cortical blindness associated with cis-platinum (II) diamminedichloride (PDD) therapy in a thirty-year-old man.

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Seizures and transient cortical blindness associated with cis-platinum (II) diamminedichloride (PDD) therapy in a thirty-year-old man.