Oral treatment with etoposide in small cell lung cancer – dilemmas and solutions
Etoposide is a chemotherapeutic agent, widely used for the treatment of various malignancies, including small cell lung cancer (SCLC), an aggressive disease with poor prognosis. Oral etoposide administration exhibits advantages for the patient as well as economic benefits. However, widespread use of oral etoposide is limited by incomplete and variable bioavailability. Variability in bioavailability was observed both within and between patients. This suggests that some patients may experience suboptimal tumor cytotoxicity, whereas other patients may be at risk for excess toxicity.
Numerous studies have shown that bioavailability of etoposide is influenced by genetic, physiological and environmental factors. Several strategies were explored to improve bioavailability and to reduce pharmacokinetic variability of oral etoposide, including desired and undesired drug interactions (e.g. with ketoconazole), development of suitable drug delivery systems, use of more water-soluble prodrug of etoposide, and influence on gastric emptying.
A few studies compared safety and efficacy of oral vs. intravenous etoposide regimen in SCLC. The majority of studies showed that the oral and intravenous schedules of etoposide did not result in significant differences in treatment outcome. Results of toxicity are inconclusive – some studies showed greater rate of toxicity in intravenous etoposide treatment schedule, while the other showed the oral etoposide treatment schedule to be inferior.
Attempts to adjust oral etoposide dose to each individual patient are currently based on individual bioavailability data and TDM approach, on limited population sampling and estimation of individual pharmacokinetic parameters by Bayesian method and on pharmacogenetic analysis. To explore the accuracy of these methods in oral etoposide dose adjustements in SCLC patients further studies are urgently needed.