Etoposide dosage

Joel SP, Shah R, Slevin ML. Etoposide dosage and pharmacodynamics. Cancer Chemother Pharmacol 1994 34(Suppl) S69-75. 

When asparaginase is administered to a patient witii diabetes, die risk for hyperglycemia is increased a dosage adjustment of die oral antidiabetic drug may be necessary. Glucocorticoids decrease die effectiveness of aldesleukin. When aldesleukin is administered witii antihypertensive drugs, tiiere is an additive hypotensive effect Etoposide may decrease the immune response to live viral vaccines. 

Etoposide causes multiple DNA double-strand breaks by inhibiting topoisomerase II. The pharmacokinetics of etoposide are described by a two-compartment model, with an a half-life of 0.5 to 1 hour and a (5 half-life of 3.4 to 8.3 hours. Approximately 30% of the dose is excreted unchanged by the kidney.16 Etoposide has shown activity in the treatment of several types of lymphoma, testicular and lung cancer, retinoblastoma, and carcinoma of unknown primary. The intravenous preparation has limited stability, so final concentrations should be 0.4 mg/mL. Intravenous administration needs to be slow to prevent hypotension. Oral bioavailability is approximately 50%, so oral dosages are approximate two times those of intravenous doses however, relatively low oral daily dosages are used for 1 to 2 weeks. Side effects include mucositis, myelosuppression, alopecia, phlebitis, hypersensitivity reactions, and secondary leukemias. 

The RT consisted of 45 Gy in 3 wk using 1.5 Gy bid concurrent with either cisplatin/etoposide or carboplatin/vindesine after the same drugs had been given alone at higher dosage. Acute toxicity was acceptable and treatment-related deaths were 9% or... 

In several studies, intravenous amifostine (910 mg/m ) preserved glomerular filtration rate when it was co-administered with cisplatin-containing regimens (213). Even after two cycles containing intravenous cisplatin 50 mg/m plus intravenous ifosfamide and etoposide or paclitaxel, glomerular filtration rate can fall by more than 30%, but concomitant use of amifostine prevented this. Even lower dosages of intravenous amifostine (for example 740 mg/m ) may be effective (220,221). 

At low doses of oral etoposide (for example 50-100 mg), the systemic availability averages 66%, and at higher dosages (100 mg/m and over) 47%. If etoposide phosphate is used, the values are higher (range 66-84%) (68-73). 

In patients with very severe forms of renal insufficiency, only moderate amounts of etoposide can be eliminated by hemodialysis (90). In patients with brain metastases, high intravenous dosages of etoposide may be... 

There is large interindividual variability in etoposide plasma concentrations with conventional dosages, and some authors have suggested that plasma concentration monitoring would reduce the pharmacokinetic variability and optimize outcomes (93,94). 

Neurotoxicity occurs in under 1% of patients who receive teniposide or etoposide, and is more common after high dosages. Adverse nervous system effects, including headache, transient mental confusion, and vertigo, may be related to the blood alcohol concentration, since teniposide and etoposide formulations contain alcohol (103). 

Peripheral neuropathy, mainly mild and infrequent, has been observed after conventional dosages of etoposide and teniposide. However, during combination therapy with etoposide and vinca alkaloids, more serious forms of peripheral neuropathy have been reported. Of 142 patients with autologous bone marrow transplantation given high-dose etoposide (for example 60 mg/kg combined with melphalan), six developed grade 2-3 polyneuropathy starting 2-8 weeks after transplantation. 

Valspodar significantly increased the AUC and half-life of etoposide, and dosage reductions of up to 66% are required to minimize toxicity when these drugs are used together. 

Holthuis JJ, Van de Vyver FL, van Oort WJ, Verleun H, Bakaert AB, De Broe ME. Pharmacokinetic evaluation of increasing dosages of etoposide in a chronic hemodialysis patient. Cancer Treat Rep 1985 69(ll) 1279-82. 

Oral administration of etoposide results in variable absorption that averages about 50%. After intravenous injection, peak plasma concentrations of 30 pg/mL are achieved there is a biphasic pattern of clearance with a terminal half-hfe of about 6 to 8 hours in patients with normal renal function. Approximately 40% of an administered dose is excreted intact in the urine, hi patients with compromised renal function, dosage should be reduced in proportion to the reduction in... 

Teniposide (Vumon) is administered intravenously. It has a multiphasic pattern of clearance from plasma. After distribution, half-lives of 4 hours and 10 to 40 hours are observed. Approximately 45% of the drug is excreted in the urine, but in contrast to etoposide, as much as 80% is recovered as metabolites. Anticonvulsants such as pheny-toin increase the hepatic metabolism of teniposide and reduce systemic exposure. Dosage does not need to be reduced for patients with impaired renal function. 

The UK manufacturer of aprepitant recommends caution when it is used with antineoplastics that are metabolised by CYP3A4, particularly irinotecan, because of the possibility of increased toxicity with this drug. They also mention that etoposide, vinoreibine, docetaxel, paclitaxel, ifosfamide, imatinib, vinblastine and vincristine, were given without dosage adjustment for potential interactions, but as this was not a formal interaction study they recommend caution. However, with intravenous docetaxel, it appears that no important changes in pharmacokinetics occur, and therefore dosage adjustments are unlikely to be needed for this drug,... 

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