Vzorci predpisovanja metformina in paracetamola ter povezave z izidi zdravljenja z zaviralci imunskih kontrolnih točk pri bolnikih z nedrobnoceličnim pljučnim rakom

Marinčič, Nuša (author), Knez, Lea (mentor), Japelj, Nuša (comentor)

Nedrobnocelični pljučni rak (NDPR) je rak z visoko umrljivostjo. Razmeroma nov tip zdravljenja predstavlja imunoterapija z zaviralci imunskih kontrolnih točk (ZIKT). Uspešnost zdravljenja z ZIKT se pri bolnikih razlikuje in je odvisna od različnih dejavnikov, med drugim od sestave in delovanja črevesne mikrobiote. Predpostavlja se, da nekatera zdravila, kot je metformin, spremenijo sestavo črevesne mikrobiote, kar bi lahko povzročilo slabši odziv na zdravljenje z ZIKT. Prav tako na izide zdravljenja z ZIKT morda vpliva tudi paracetamol, ki je prepoznan kot potencialni zaviralec protitumorske imunosti. Namen dela je opisati vzorce predpisovanja metformina in paracetamola pri bolnikih z NDPR, ki so se zdravili z ZIKT na Kliniki Golnik. Zanimalo nas bo tudi, če so vzorci predpisovanja metformina in paracetamola povezani z izidi zdravljenja z ZIKT. V retrospektivno raziskavo smo vključili 369 bolnikov z napredovalim NDPR, ki so med julijem 2015 in decembrom 2022 prejemali zdravljenje z ZIKT na Kliniki Golnik. Podatke smo pridobili iz bolnišnične zbirke medicinskih podatkov BIRPIS Klinike Golnik. Za statistično analizo smo uporabili programe MS Excel, SPSS in RStudio. Zdravilo z metforminom je v obdobju od enega leta pred uvedbo do zadnje aplikacije ZIKT dvignilo 41 (11,1 %) bolnikov. Povprečno so v obdobju enega leta pred uvedbo do uvedbe ZIKT dvignili 0,94 DDD (dnevni definiran odmerek – ang. daily defined dose), in sicer 1880 mg. Analiza preživetja ni pokazala povezave med OS (celokupno preživetje – ang. overall survival) in dvigom metformina (Kaplan-Meier, p = 0,628) ali povprečnim DDD metformina (Coxova regresija, p = 0,544) v obdobju enega leta pred uvedbo do uvedbe ZIKT. Večina bolnikov (283; 76,7 %) je v obdobju enega leta pred uvedbo do zadnje aplikacije ZIKT imela dvig zdravila s paracetamolom. V obdobju enega leta pred uvedbo do uvedbe ZIKT so bolniki dvignili povprečno 0,04 DDD (120 mg). Analiza preživetja ni pokazala povezave med OS in dvigom paracetamola v obdobju enega leta pred uvedbo do uvedbe ZIKT (Kaplan-Meier, p = 0,199), v obdobju ± 60 dni (Kaplan-Meier, p = 0,700) ali ± 30 dni (Kaplan-Meier, p = 0,829) glede na uvedbo ZIKT, niti s povprečnim DDD paracetamola v obdobju enega leta pred uvedbo do uvedbe ZIKT (Coxova regresija, p = 0,855). V obdobju enega leta pred uvedbo do zadnje aplikacije ZIKT zelo malo bolnikov uporablja metformin, nasprotno pa paracetamol uporablja večina, vendar v majhnem celokupnem odmerku. V raziskavi nismo našli povezave med OS bolnikov in uporabo metformina ali paracetamola v tem obdobju, možen vzrok za to pa je premajhno število bolnikov.

• Language: Slovenian
• Keywords: nedrobnocelični pljučni rak, zaviralci imunskih kontrolnih točk, metformin, paracetamol, vzorci predpisovanja, izidi zdravljenja z imunoterapijo
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2025
• PID: 20.500.12556/RUL-168597
• Publication date in RUL: 18.04.2025

Secondary language

• Language: English
• Title: Prescribing patterns of metformin and paracetamol and their association with treatment outcomes with immune checkpoint inhibitors in patients with non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) has a high mortality. A relatively new type of treatment for NSCLC is immunotherapy with immune checkpoint inhibitors (ICIs). Response of ICI treatment varies among patients and is dependent on various factors, including the composition and function of gut microbiota. It is assumed that some drugs, such as metformin, change the composition of the gut microbiota, which could lead to a poorer response to ICIs. Treatment outcomes could also be affected by paracetamol, which is recognized as a potential inhibitor of antitumor immunity. The aim of this study is to describe the prescribing patterns of metformin and paracetamol in patients with NSCLC treated with ICI at the Golnik Clinic. We will also evaluate association of prescribing patterns of metformin and paracetamol with the outcomes of ICI treatment. Our retrospective study included 369 patients with advanced NSCLC who received ICI treatment at the Golnik Clinic between July 2015 and December 2022. The data were obtained from the BIRPIS hospital medical database of the Golnik Clinic. Statistical analysis was performed in programs MS Excel, SPSS and RStudio. Medicine with metformin was prescribed in 41 (11.1%) patients in the period of one year before the initiation until the last application of ICI. On average, included patients received 0.94 DDD (daily defined dose), corresponding to 1880 mg, during one year before the initiation of ICI until initiation of ICI. Analysis showed no association between OS (overall survival) and metformin use (Kaplan-Meier, p = 0.628) or the average DDD of metformin (Cox regression, p = 0.544) during one year before the initiation of ICI until initiation of ICI. The majority of patients (283; 76.7%) had paracetamol prescription during one year before the initiation of ICI to the last application of ICI. During one year before the introduction of ICI, the average DDD was 0.04 (120 mg). Analysis showed no association between OS and paracetamol use during one year before the initiation of ICI until initiation of ICI (Kaplan-Meier, p = 0.199), in the period of ± 60 days (Kaplan-Meier, p = 0.700) or ± 30 days (Kaplan-Meier, p = 0.829) according to initiation of ICI, nor with the average DDD of paracetamol during one year before the initiation of ICI until initiation of ICI (Cox regression, p = 0.855). In the period of one year before the initiation of ICI until the last application of ICI, very few patients use metformin, while most patients use paracetamol in lower doses. In our study, we did not find an association between OS and the use of metformin or paracetamol during this period, a possible reason for this is the small number of patients in the study.

• Keywords: non-small cell lung cancer, immune checkpoint inhibitors, metformin, paracetamol, prescribing patterns, immunotherapy treatment outcomes