| Author/Editor | Režonja, Renata; Knez, Lea; Čufer, Tanja; Mrhar, Aleš | |
| Title | Oral treatment with etoposide in small cell lung cancer - dilemmas and solution | |
| Type | članek | |
| Vol. and No. | Letnik 47, št. 1 | |
| Publication year | 2013 | |
| Volume | str. 1-13 | |
| ISSN | 1318-2099 - Radiology and oncology | |
| Language | eng | |
| Abstract | Background. 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 quality of life of 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 atrisk for excess toxicity. Conclusions. The article highlights dilemmas as well as solutions regarding oral treatment with etoposide by presenting and analyzing relevant literature data. 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. In addition to genotype-based dose administration, etoposide is suitable for pharmacokinetically guided dosing, which enables dose adjustments in individual patient. Further, it is established that oral and intravenous schedules of etoposide in SCLC patients do not result in significant differences in treatment outcome, while results of toxicity are inconclusive. To conclude, the main message of the article is that better prediction of the pharmacokinetics of oral etoposide may encourage its wider use in routine clinical practice.Izhodišča. Etopozid je protitumorna učinkovina, ki jo pogosto uporabljamo za zdravljenje različnih rakavih obolenj, vključno z drobnoceličnim pljučnim rakom. Ta je agresivni rak s slabo napovedjo poteka bolezni. Peroralno vnašanje etopozida ima veliko prednosti tako z vidika kakovosti življenja bolnika kakor tudi z vidika obvladovanja stroškov. Uporaba etopozida pa je omejena zaradi nepopolne absorpcije ter velike intra- in inter-individualne spremenljivosti biološke uporabnosti. To lahko pri nekaterih bolnikih privede do zmanjšane učinkovitosti ali povečane toksičnosti. Zaključki. Članek s pregledom in analizo literaturnih podatkov predstavlja dileme in rešitve gledeperoralnega zdravljenja z etopozidom. Rezultati številnih raziskav so pokazali, da na biološko uporabnost etopozida vplivajo genetski, fiziološki in okoljski dejavniki. Poznamo številne pristope za izboljšanje biološke uporabnosti in zmanjšanje farmakokinetične spremenljivosti peroralnega etopozida. To so želene in neželene interakcije (npr. s ketokonazolom), razvojustreznih dostavnih sistemov, uporaba predzdravila, ki je bolj vodotopno od etopozida in vpliv na hitrost praznjenja želodca. Etopozid je primerna zdravilna učinkovina za odmerjanje na osnovi poznavanja farmakokinetike in genotipa, kar omogoča tudi prilagajanje odmerka pri posameznemu bolniku. Ugotovili so, da se učinkovitost peroralnega in intravenskega zdravljenja z etopozidom pri bolnikih z drobnoceličnim pljučnim rakom značilno ne razlikuje, medtem ko so si rezultati primerjav toksičnosti nasprotujoči. Glavno sporočilo članka je, da boljša napovedljivost farmakokinetike peroralnega etopozida omogoča večjo uporabo le-tega v rutinski klinični praksi. | |
| Keywords | farmakokinetika drobnocelični pljučni rak kemoterapevtiki zdravljenje etopozid oral etoposide bioavailability pharmacokinetic variability small cell lung cancer treatment |