J 2020

Therapeutic Drug Monitoring of Sunitinib in Gastrointestinal Stromal Tumors and Metastatic Renal Cell Carcinoma in Adults-A Review

DEMLOVÁ, Regina, Miroslav TURJAP, Ondřej PEŠ, Katarína KOSTOLANSKÁ, Jan JUŘICA et. al.

Basic information

Original name

Therapeutic Drug Monitoring of Sunitinib in Gastrointestinal Stromal Tumors and Metastatic Renal Cell Carcinoma in Adults-A Review

Authors

DEMLOVÁ, Regina (203 Czech Republic, belonging to the institution), Miroslav TURJAP (203 Czech Republic), Ondřej PEŠ (203 Czech Republic, belonging to the institution), Katarína KOSTOLANSKÁ (703 Slovakia, belonging to the institution) and Jan JUŘICA (203 Czech Republic, guarantor, belonging to the institution)

Edition

THERAPEUTIC DRUG MONITORING, PHILADELPHIA, LIPPINCOTT WILLIAMS & WILKINS, 2020, 0163-4356

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.681

RIV identification code

RIV/00216224:14110/20:00115974

Organization unit

Faculty of Medicine

UT WoS

000523689800003

Keywords in English

sunitinib; N-desethylsunitinib; mRCC; GIST; therapeutic drug monitoring; toxicity-adjusted dosing

Tags

International impact, Reviewed
Změněno: 4/4/2022 13:01, Mgr. Tereza Miškechová

Abstract

V originále

Background: Sunitinib is an inhibitor of multiple receptor tyrosine kinases and is a standard-of-care treatment for advanced and metastatic renal cell carcinoma and a second-line treatment in locally advanced inoperable and metastatic gastrointestinal stromal tumors. A fixed dose of the drug, however, does not produce a uniform therapeutic outcome in all patients, and many face adverse effects and/or toxicity. One of the possible causes of the interindividual variability in the efficacy and toxicity response is the highly variable systemic exposure to sunitinib and its active metabolite. This review aims to summarize all available clinical evidence of the treatment of adult patients using sunitinib in approved indications, addressing the necessity to introduce proper and robust therapeutic drug monitoring (TDM) of sunitinib and its major metabolite, N-desethylsunitinib. Methods: The authors performed a systematic search of the available scientific literature using the PubMed online database. The search terms were "sunitinib" AND "therapeutic drug monitoring" OR "TDM" OR "plasma levels" OR "concentration" OR "exposure." The search yielded 520 journal articles. In total, 447 publications were excluded because they lacked sufficient relevance to the reviewed topic. The remaining 73 articles were, together with currently valid guidelines, thoroughly reviewed. Results: There is sufficient evidence confirming the concentration-efficacy and concentration-toxicity relationship in the indications of gastrointestinal stromal tumors and metastatic renal clear-cell carcinoma. For optimal therapeutic response, total (sunitinib + N-desethylsunitinib) trough levels of 50-100 ng/mL serve as a reasonable target therapeutic range. To avoid toxicity, the total trough levels should not exceed 100 ng/mL. Conclusions: According to the current evidence presented in this review, a TDM-guided dose modification of sunitinib in selected groups of patients could provide a better treatment outcome while simultaneously preventing sunitinib toxicity.

Links

CZ.02.1.01/0.0/0.0/16_013/0001826, interní kód MU
(CEP code: EF16_013/0001826)
Name: CZECRIN_PRO PACIENTY - zavádění inovativních moderních terapií
Investor: Ministry of Education, Youth and Sports of the CR, Priority axis 1: Strengthening capacities for high-quality research
LM2018128, research and development project
Name: Český národní uzel Evropské sítě infrastruktur klinického výzkumu (Acronym: CZECRIN)
Investor: Ministry of Education, Youth and Sports of the CR
MUNI/A/0976/2018, interní kód MU
Name: Příspěvek chemických a biochemických metodik ke studiu molekulární podstaty vybraných patologických stavů a onemocnění
Investor: Masaryk University, Category A
MUNI/A/1167/2019, interní kód MU
Name: Příspěvek (bio)chemických technik ke studiu molekulární podstaty vybraných patologických jevů a onemocnění
Investor: Masaryk University, Category A
MUNI/A/1550/2018, interní kód MU
Name: Farmakologický výzkum v oblasti farmakokinetiky, neuropsychofarmakologie a onkologie
Investor: Masaryk University, Category A