Hydration cisplatin therapy

The greatest research effort on radiation sensitizers has focused on organic compounds however, platinum complexes conform to the hypotheses for radiation sensitizers since they are electron affinic and react preferentially with the hydrated electron in aqueous solution. Early studies of cisplatin in combination with radiation therapy suggested a synergistic effect in antitumor activity (50,51). Much of the initial data were obtained using cells in tissue culture (52), these data indicated that the potential of cisplatin to inhibit repair of radiation-induced damage to DNA could be an important contributor to the enhanced tumor cell killing seen in vivo by the combination of these two modes of treatment. 

IFOSFAMIDE CISPLATIN t risk of neurotoxicity, haematotoxicity and tubular nephrotoxicity of ifosfamide due to t plasma concentrations of ifosfamide Cisplatin tends to cause renal damage, which results in impaired clearance of ifosfamide Do renal function tests before initiating therapy and during concurrent therapy, and adjust dosage based on creatinine clearance values. Advise patients to drink plenty of water -vigorous hydration - and consider mesna therapy for renal protection... 

RITUXIMAB CISPLATIN t risk of severe renal failure Uncertain, possibly due to effects of tumour lysis syndrome (which is a result of massive breakdown of cancer cells sensitive to chemotherapy). Features include hyperkalaemia, hyperuricaemia, hyperphosphataemia and hypocalcaemia Monitor renal function closely. Hydrate with at least 2 L of fluid before, during and after therapy. Monitor potassium and magnesium levels in particular and correct deficits. Do an ECG as arrhythmias may accompany tumour lysis syndrome... 

There are some serious drawbacks to the use of cis-platin in anticancer therapy. Severe toxicity problems occur, such as failure of the kidneys and bone marrow (nephrotoxicity and hematoxicity), nausea, intractable vomiting (emesis), peripheral neuropathy, deafness (ototoxicity), and seizures. These toxic side effects of cisplatin limit the dose that can be administered to patients typical doses are 100 mg day for up to five consecutive days. The nephrotoxicity can be reduced by hydration and diuresis. 5-HT3-receptor blockers control nausea and emesis. Much effort has been devoted to the development of chemopro-tective agents, which alleviate the side effects on normal tissues without compromising antitumor activity - mainly sulfur-containing agents such as sodium dithiocarbamate (Naddtc), 2-mercaptoethanesulphonate (mesna), and amifos-tine (WR-2721). Amifostine has recently been approved for coadministration with cisplatin, which reduces nephro- and neurotoxicity. ... 

However, appropriate hydration and the sulfhydryl compound mesna are effective in decreasing the urotox-icity of ifosfamide [100, 101]. Less frequently asymptomatic renal functional abnormalities are reported following treatment with ifosfamide when used at a dose below 1.5 gr/m body skin surface [102, 103]. Acute renal failure secondary to tubular necrosis has been described when high-dose therapy [>5 gr/ m2] is administered, especially if patients were treated previously with cisplatin [104,105]. With escalating doses of a 96 hours infusion of ifosfamide, renal toxicity is dose limiting at 18 gr/ m2 [106]. 

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