Cisplatin adverse effects

Nephrotoxins (N) orototoxins (0) (eg., amphotericin B (N), cisplatin (N/0), cyclosporine (N), furosemide (0), NSAIDs (N), radio contrast (N), vancomycin (N) Additive adverse effects Monitor aminoglycoside SDC and renal function... 

The major advantage of carboplatin over cisplatin is a markedly reduced risk of toxicity to the kidneys, peripheral nerves, and hearing additionally, it produces less nausea and vomiting. It is, however, more myelo-suppressive than cisplatin. Other adverse effects include anemia, abnormal liver function tests, and occasional allergic reactions. 

The identification of the mechanisms of cisplatin translesion synthesis should allow the refinement of strategies aimed at minimizing the adverse effects of this cellular process. 

One of the adverse effects of clinically used venlafaxine 10 is nausea that may be connected with its mixed serotonin/noradrenaline profile. The selective noradrenaline-reuptake inhibitor sila-velafaxime (R)-ll at oral administration effectively inhibited emetic episodes caused by emetogen (morphine) in the ferret emesis model (06BMCL2555). Intraperitoneally administered sila-venlafaxine (R)-ll was able to reduce cisplatin-induced acute and delayed emesis (08TAP369). 

In a phase III trial in 190 patients with metastatic melanoma, sequential chemotherapy with dacarbazine, cisplatin, and vinblastine plus interferon alfa and aldesleukin modestly increased the response rates and produced considerably more frequent and severe adverse effects than chemotherapy alone (128). In particular, severe episodes of anemia and thrombocytopenia that required blood or platelet transfusions were 2-6 times more frequent in the chemotherapy group. 

In a phase-II study, 14 patients with metastatic cervical cancer or recurrent disease not eligible for surgery or radiation received bryostatin 1 50-65 pg/m -I- cisplatin 50mg/m. The most common adverse effects were myalgia, anemia, and nausea or vomiting one patient had a hypersensitivity reaction and one developed grade 3 nephrotoxicity (9). 

Of the clinically established platinum compounds, cisplatin has the most toxic effects on organs like the nervous system, the organ of Corti, and the kidneys in a dose-dependent fashion. The dose per cycle has therefore usually been limited to 100-120 mg/m intravenously, in order to avoid drug-induced irreversible organ dysfunction (12,13). The complete spectrum of late or long-term adverse effects of cisplatin in survivors of testicular cancer has been reviewed (32). 

Like carboplatin, oxaliplatin does not usually cause nephrotoxicity. In addition, both drugs are only moderately emetogenic, in contrast to cisplatin. The most important dose-limiting adverse effect of oxaliplatin is a sensory peripheral neuropathy, which has two different forms ... 

Ocular effects, including optic neuritis, papilledema, and retrobulbar neuritis, are uncommon adverse effects of cisplatin-containing cancer chemotherapy. The risk of retinal toxicity is restricted to high-dose cisplatin therapy (for example 200 mg/m over 5 days) and can result in blurred vision and altered color perception, which can persist for several months. In contrast to cisplatin, carbo-platin is seldom involved in drug-induced visual disturbances. In two cases there was a relation between the administration of carboplatin (800-1200 mg/m ) and the occurrence of chnical cortical blindness (122). However, both patients had impaired renal function before the start of therapy with carboplatin. 

Nausea, vomiting, and diarrhea are common adverse effects of oxaliplatin and carboplatin, but they are generally mild to moderate, and both are less emetogenic than cisplatin. However, patients who have previously received cisplatin may be at greater risk of vomiting with carboplatin or oxaliplatin (1,8,9). 

Biomarkers of exposure to xenobiotics causing nephrotoxicity may take one of several forms. The measurement of blood or tissue levels of drugs known to have adverse effects on the kidney, such as cyclosporine, aminoglycoside antibiotics, or lithium, is a standard practice. The awareness of the total amount of drug administered is frequently important when considering amphotericin and cisplatin nephrotoxicity. More difficulty is encountered with the determination of the body burden of a toxicant, although under certain circumstances such a value is necessary to determine the health effects of exposure to heavy metals such as cadmium and lead, and some analgesics [2]. 

Carboplatin has a much more favorable adverse effect profile than cisplatin however, it does exhibit myelosuppression. 

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