Pharmacokinetic comparison of oral and intravenous etoposide in patients treated with the CHOEP-regimen for malignant lymphomas.

Abstract

BACKGROUND:

The addition of etoposide to the CHOP protocol (CHOEP) has been shown to improve outcome in patients with aggressive non-Hodgkin's lymphoma. The intravenous administration of etoposide on three consecutive days represents a logistic problem and needs resources particular in the outpatient setting. This could be avoided by using etoposide capsules on days 2 and 3. However, the oral administration of cytotoxic agents is often affected by variable absorption and drug interactions.

PATIENTS AND METHODS:

We investigated the pharmacokinetic equivalency of oral and intravenous etoposide in ten patients (male, n=7; female, n=3; median age 56 years) with aggressive lymphomas. Treatment consisted of standard CHOP plus etoposide 100 mg/m2 given intravenously on day 1, and 200 mg/m2 orally on days 3 and 4. Samples from blood and urine were taken on days 1 (i.v. study) and 3 (p.o. study) before and after etoposide administration. Etoposide levels were determined by high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were calculated with the TOPFIT computer program.

RESULTS:

Mean peak plasma level after intravenous etoposide was significantly higher compared to oral administration (16.3+/-3.7 vs. 12.0+/-4.2 microg/ml; P=0.015). The mean bioavailability of oral etoposide was 58+/-15% with an interpatient variability of 26%. Significant differences of bioavailability of oral etoposide between the used dose levels (350, 400 and 450 mg) were not observed. Mean AUC after a 100 mg/m2 intravenous and a 200 mg/m2 oral dose of etoposide were 74.0+/-18.3 and 84.9+/-29.6 microg h/ml (P=0.481). Interpatient variability of AUC was 25% for the intravenous route and 35% after oral intake. Urinary etoposide excretion as percentage of administered dose was 39.4+/-10.6% after intravenous infusion versus 35.4+/-9.4% after oral intake (P=0.422). Renal clearance was also very similar with intravenous and oral route (18.5+/-7.4 vs. 16.7+/-6.6 ml/min; P=0.546).

CONCLUSION:

The equivalency of AUC after 200 mg/m2 of oral and 100 mg/m2 of intravenous etoposide support the use of the oral preparation in patients treated with the CHOEP regimen, which makes the chemotherapy more convenient for the patients and help to reduce costs.

• Authors: Frank P Kroschinsky, Kai Friedrichsen, Juliane Mueller, Stefan Pursche, Mathias Haenel, Roland Prondzinsky, Gerhard Ehninger, Eberhard Schleyer
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 61 Issue 5 Pg. 785-90 (Apr 2008) ISSN: 0344-5704 [Print] Germany
• PMID: 17579865 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Vincristine
• Etoposide
• Doxorubicin
• Cyclophosphamide
• Prednisolone

Topics

• Administration, Oral
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Area Under Curve
• Biological Availability
• Chromatography, High Pressure Liquid
• Cyclophosphamide (administration & dosage)
• Dose-Response Relationship, Drug
• Doxorubicin (administration & dosage)
• Etoposide (administration & dosage, pharmacokinetics)
• Female
• Humans
• Infusions, Intravenous
• Lymphoma, Non-Hodgkin (drug therapy)
• Male
• Middle Aged
• Prednisolone (administration & dosage)
• Software
• Vincristine (administration & dosage)