<unk>  has a number of side effects that can limit its use: * Nephrotoxicity (kidney damage) is the primary dose-limiting side effect and is of major clinical concern.<unk>  selectively accumulates into the proximal tubule via basolateral-to-apical transport, where it disrupts mitochondrial energetics and endoplasmic reticulum Ca2+ homeostasis and stimulates reactive oxygen species and pro-inflammatory cytokines. Multiple mitigation strategies are being explored clinically and pre-clinically, including hydration regimens, amifostine, transporter inhibitors, antioxidants, anti-inflammatories, and epoxyeicosatrienoic acids and their analogues. * Neurotoxicity (nerve damage) can be anticipated by performing nerve conduction studies before and after treatment. Common neurological side effects of<unk>  include visual perception and hearing disorder, which can occur soon after treatment begins. While triggering apoptosis through interfering with DNA replication remains the primary mechanism of<unk> , this has not been found to contribute to neurological side effects. Recent studies have shown that<unk>  noncompetitively inhibits an archetypal, membrane-bound mechanosensitive sodium-hydrogen ion transporter known as NHE-1. It is primarily found on cells of the peripheral nervous system, which are aggregated in large numbers near the ocular and aural stimuli-receiving centers. This noncompetitive interaction has been linked to hydroelectrolytic imbalances and cytoskeleton alterations, both of which have been confirmed in vitro and in vivo. However, NHE-1 inhibition has been found to be both dose-dependent (half-inhibition = 30 μg/mL) and reversible. * Nausea and vomiting:<unk>  is one of the most emetogenic chemotherapy agents, but this symptom is managed with prophylactic antiemetics (ondansetron, granisetron, etc.) in combination with corticosteroids. Aprepitant combined with ondansetron and dexamethasone has been shown to be better for highly emetogenic chemotherapy than just ondansetron and dexamethasone. * Ototoxicity (hearing loss): there is at present no effective treatment to prevent this side effect, which may be severe, although there is ongoing investigation of acetylcysteine injections as a preventative measure. Audiometric analysis may be necessary to assess the severity of ototoxicity. Other drugs (such as the aminoglycoside antibiotic class) may also cause ototoxicity, and the administration of this class of antibiotics in patients receiving<unk>  is generally avoided. The ototoxicity of both the aminoglycosides and<unk>  may be related to their ability to bind to melanin in the stria vascularis of the inner ear or the generation of reactive oxygen species. * Electrolyte disturbance:<unk>  can cause hypomagnesaemia, hypokalaemia and hypocalcaemia. The hypocalcaemia seems to occur in those with low serum magnesium secondary to<unk> , so it is not primarily due to the<unk> . * Hemolytic anemia can be developed after several courses of<unk> . It is suggested that an antibody reacting with a<unk> -red-cell membrane is responsible for hemolysis.
Cisplatin
Ifosfamide
Bleomycin
Carboplatin
Vincristine
Mitoxantrone
Etoposide
Daunorubicin