Cisplatin therapy

This may be given orally, intravenously (IV) or intramuscularly (IM) the dose depends on the indication. For postoperative nausea and vomiting, common regimens are either 8 mg orally before or 4 mg IV intra-operatively. Increasing the dose does not significantly improve its efficacy. The doses used with chemotherapy are larger, especially with cisplatin therapy, e.g. 8 mg IV before, then 8 mg 2-4 hours later then 8 mg 12-hourly for 5 days. 

Experiments with animals demonstrate that DDTC could be used in conjunction with cisplatin chemotherapy325,326. For instance, pretreatment with DDTC protects against the nephrotoxicity of cisplatin therapy Wysor et al.327 have demonstrated the trypanocidal potential of cisplatin and tetraethylthiuram disulphide, the disulphide of DDTC... 

Milacic, R., Cemazar, M., Sersa, G. Determination of platinum in tumor tissues after cisplatin therapy by electrothermal atomic absorption spectrometry. J. Pharm. Biomed. Anal. 16, 343-348 (1997)... 

El Amrani M, Heinzlef O, Debroucker T, Roullet E, Bousser MG, Amarenco P. Brain infarction following 5-fluorouracil and cisplatin therapy. Neurology 1998 51(3) 899-901. 

In five patients cerebral herniation followed cisplatin therapy (94). However, all had evidence of an intracerebral tumor with mass effect and the herniation of the brain was thought to be multifactorial rather than directly attributable to cisplatin. 

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. 

About 30% of patients treated with cisplatin have been reported to have some degree of anosmia, which in 1% is severe or complete the sense of smell returns to normal within 3-4 months of completing cisplatin therapy (158). 

Hyperosmolar non-ketotic hyperglycemia occurred in a 61-year-old patient 6 days after a first cycle of cisplatin therapy (161). The patient recovered with conventional conservative management. 

Hjq)onatremia is rare, and persistent hyponatremia very rare in patients taking cisplatin (162). In a detailed description of the biochemical abnormalities that can result from renal tubular dysfunction after cisplatin therapy, it was noted that hypocalciuria is more common than hypomagnesemia, and that there tends to be a state of reduced serum bicarbonate. The most severe renal tubular damage caused by cisplatin is characterized by hypocalciuria, total body magnesium deficiency, and hypokalemic metabolic alkalosis (163). 

Samuels BL, Vogelzang NJ, Kennedy BJ. Vascular toxicity following vinblastine, bleomycin, and cisplatin therapy for germ cell tumours. Int J Androl 1987 10(l) 363-9. 

Riggs JE, Ashraf M, Snyder RD, Gutmann L. Prospective nerve conduction studies in cisplatin therapy. Ann Neurol 1988 23(l) 92-4. 

Wang MY, Arnold AC, Vinters HV, Glasgow BJ. Bilateral blindness and lumbosacral myelopathy associated with high-dose carmustine and cisplatin therapy. Am J Ophthalmol 2000 130(3) 367-8. 

Al-Tweigeri T, Magliocco AM, DeCoteau JF. Cortical blindness as a manifestation of hypomagnesemia secondary to cisplatin therapy case report and review of literature. Gynecol Oncol 1999 72(l) 120-2. 

Gamble GE, Tyrrell P. Acute stroke following cisplatin therapy. Clin Oncol (R Coll Radiol) 1998 10(4) 274-5. 

Cvitkovic E. Cumulative toxicities from cisplatin therapy and current cytoprotective measures. Cancer Treat Rev 1998 24(4) 265-81. 

A variety of platinum (Pt)-containing antineoplastic agents are used in chemotherapy, typified by cisplatin cts-dichlorodiammineplatinum dihydrate) All of diese compounds have some nephrotoxicity that is related to the concentration of Pt circulating in the blood. Although it is not common to measure Pt concentrations in all patients receiving cisplatin therapy, quantification of Pt concentrations in patients with reduced renal function can help identify whether the Pt is the cause of the compromised renal function. Peak serum concentrations greater than... 

Fig. 4 5-year chance of having normal hearing following cisplatin therapy related to having 0,1,2, or 3 or more risk alleles for cisplatin-induced ototoxicity percentages estimated based on data derived by our group and published in Nat Genet 2009 41 1345-9... 

Niederle N, Schutte J, Schmidt CG (1986) Crossover comparison of the antiemetic efficacy of nabilone and alizapride in patients with nonseminomatous testicular cancer receiving cisplatin therapy. Klin Wochenschr 64 362-365... 

Recommendation 4. For the prevention of delayed emesis after cisplatin therapy in adults, dexamethasone with metoclopramide or a SSRI is recommended. Thechoice of agent should be based on patient-specific factors and cost. For delayed emesis after cyclophosphamide, doxorubicin, or carboplatin therapy, a SSRI with dexamethasone is recommended. In pediatric patients, chlorpromazine, lorazepam, or a SSRI can be used in combination with a corticosteroid. 

Acute renal failure due to cisplatin therapy is usually partially reversible with time and supportive care, including dialysis. Serummag-nesium concentrations should be monitored frequently and hypomagnesemia corrected (see Chap. 50). Hypocalcemia and hypokalemia may be difficult to reverse until hypomagnesemia is corrected. Progressive chronic kidney disease due to cumulative toxicity may not be reversible and in some cases may require chronic dialysis support. 

Mutagenic compounds either react with or can be converted to compounds that react with DNA to form DNA adducts. The cisplatin DNA adducts cause errors during DNA replication, which lead to mutations, especially G —> T transversion [15]. Such mutations may be responsible for second malignancies that arise after cisplatin therapy [16]. 

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