Top

International Journal of Clinical Oncology

Published in:

01-07-2020 | Urinalysis | Original Article

Urinalysis by combination of the dipstick test and urine protein–creatinine ratio (UPCR) assessment can prevent unnecessary lenvatinib interruption in patients with thyroid cancer

Authors: Chie Masaki, Kiminori Sugino, Sakiko Kobayashi, Junko Akaishi, Kiyomi Y. Hames, Chisato Tomoda, Akifumi Suzuki, Kenichi Matsuzu, Takashi Uruno, Keiko Ohkuwa, Wataru Kitagawa, Mitsuji Nagahama, Koichi Ito

Published in: International Journal of Clinical Oncology | Issue 7/2020

Abstract

Background

Proteinuria induced by lenvatinib is a class effect that occurs secondary to VEGFR suppression. Withholding of lenvatinib is required in cases with severe proteinuria. Urine protein–creatinine ratio (UPCR, g/gCre) has recently attracted attention as an alternative to 24-h urine collection for assessing proteinuria. The aim of this study was to examine the correlation between the results of proteinuria assessed by the dipstick test and UPCR, and to investigate the influence of proteinuria grading with UPCR on lenvatinib dose adjustment compared to that with only the dipstick test.

Method

Three hundred and ten urine samples from 63 patients with advanced thyroid cancer under treatment with lenvatinib, which were tested by both the dipstick test and UPCR were analyzed. Lenvatinib was withheld when there was evidence of CTCAE grade 3 proteinuria, and restarted when it resolved. The frequency of proteinuria, correlation between the results of the dipstick test and UPCR test, and the effect of dose withholding in cases with results of 3 + in the dipstick test were calculated.

Results

Proteinuria was seen in 56 (88.9%) patients. Of the 154 dipstick 3 + samples, only 56 (36.4%) were judged as more than 3.5 g/gCre by UPCR (grade 3 proteinuria), although none of the 1 + and only 3.7% of 2 + samples were judged as grade 3 proteinuria. We were able to prevent unnecessary lenvatinib interruption due to proteinuria in 63.6% of dipstick 3 + samples by assessment of UPCR.

Conclusions

Urinalysis by combination of the dipstick test and UPCR assessment might be a better strategy for preventing unnecessary interruption of lenvatinib.

Stjepanovic N, Capdevila J (2014) Multikinase inhibitors in the treatment of thyroid cancer: specific role of lenvatinib. Biologics 8:129–139. https://doi.org/10.2147/BTT.S39381 CrossRefPubMedPubMedCentral

Izzedine H, Massard C, Spano JP et al (2010) VEGF signalling inhibition-induced proteinuria: mechanisms, significance and management. Eur J Cancer 46(2):439–448. https://doi.org/10.1016/j.ejca.2009.11.001 CrossRefPubMed

Salgia R (2011) Prognostic significance of angiogenesis and angiogenic growth factors in nonsmall cell lung cancer. Cancer 117(17):3889–3899. https://doi.org/10.1002/cncr.25935 CrossRefPubMedPubMedCentral

Cosmai L, Gallieni M, Liguigli W et al (2017) Renal toxicity of anticancer agents targeting vascular endothelial growth factor (VEGF) and its receptors (VEGFRs). J Nephrol 30(2):171–180. https://doi.org/10.1007/s40620-016-0311-8 CrossRefPubMed

Kitamoto Y, Tokunaga H, Miyamoto K et al (2002) VEGF is an essential molecule for glomerular structuring. Nephrol Dial Transplant 17(Suppl 9):25–27. https://doi.org/10.1093/ndt/17.suppl_9.25 CrossRefPubMed

Schlumberger M, Tahara M, Wirth LJ et al (2015) Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 372(7):621–630. https://doi.org/10.1056/NEJMoa1406470 CrossRefPubMed

Kudo M, Finn RS, Qin S et al (2018) Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 391(10126):1163–1173. https://doi.org/10.1016/S0140-6736(18)30207-1 CrossRefPubMed

Motzer RJ, Hutson TE, Glen H et al (2015) Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol 16(15):1473–1482. https://doi.org/10.1016/S1470-2045(15)00290-9 CrossRefPubMed

Capdevila J, Newbold K, Licitra L et al (2018) Optimisation of treatment with lenvatinib in radioactive iodine-refractory differentiated thyroid cancer. Cancer Treat Rev 69:164–176. https://doi.org/10.1016/j.ctrv.2018.06.019 CrossRefPubMed

10.

Ralston SH, Caine N, Richards I et al (1988) Screening for proteinuria in a rheumatology clinic: comparison of dipstick testing, 24 hour urine quantitative protein, and protein/creatinine ratio in random urine samples. Ann Rheum Dis 47(9):759–763. https://doi.org/10.1136/ard.47.9.759 CrossRefPubMedPubMedCentral

11.

Yang CY, Chen FA, Chen CF et al (2015) Diagnostic accuracy of urine protein/creatinine ratio is influenced by urine concentration. PLoS ONE 10(9):e0137460. https://doi.org/10.1371/journal.pone.0137460 CrossRefPubMedPubMedCentral

12.

Ginsberg JM, Chang BS, Matarese RA et al (1983) Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med 309(25):1543–1546. https://doi.org/10.1056/NEJM198312223092503 CrossRefPubMed

13.

Kiyota N, Schlumberger M, Muro K et al (2015) Subgroup analysis of Japanese patients in a phase 3 study of lenvatinib in radioiodine-refractory differentiated thyroid cancer. Cancer Sci 106(12):1714–1721. https://doi.org/10.1111/cas.12826 CrossRefPubMedPubMedCentral

14.

Ruggenenti P, Gaspari F, Perna A et al (1998) Cross sectional longitudinal study of spot morning urine protein:creatinine ratio, 24 hour urine protein excretion rate, glomerular filtration rate, and end stage renal failure in chronic renal disease in patients without diabetes. BMJ 316(7130):504–509. https://doi.org/10.1136/bmj.316.7130.504 CrossRefPubMedPubMedCentral

15.

Chen YT, Hsu HJ, Hsu CK et al (2019) Correlation between spot and 24h proteinuria: Derivation and validation of equation to estimate daily proteinuria. PLoS ONE 14(4):e0214614. https://doi.org/10.1371/journal.pone.0214614 CrossRefPubMedPubMedCentral

16.

Evans TRJ, Kudo M, Finn RS et al (2019) Urine protein:creatinine ratio vs 24-hour urine protein for proteinuria management: analysis from the phase 3 REFLECT study of lenvatinib vs sorafenib in hepatocellular carcinoma. Br J Cancer. https://doi.org/10.1038/s41416-019-0506-6 CrossRefPubMedPubMedCentral

17.

Levey AS, Eckardt KU, Tsukamoto Y et al (2005) Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 67(6):2089–2100. https://doi.org/10.1111/j.1523-1755.2005.00365.x CrossRef

18.

Cho JY, Paik YH, Lim HY et al (2013) Clinical parameters predictive of outcomes in sorafenib-treated patients with advanced hepatocellular carcinoma. Liver Int 33(6):950–957. https://doi.org/10.1111/liv.12168 CrossRefPubMed

19.

Akutsu N, Sasaki S, Takagi H et al (2015) Development of hypertension within 2 weeks of initiation of sorafenib for advanced hepatocellular carcinoma is a predictor of efficacy. Int J Clin Oncol 20(1):105–110. https://doi.org/10.1007/s10147-014-0691-5 CrossRefPubMed

20.

Cavalieri S, Cosmai L, Genderini A et al (2018) Lenvatinib-induced renal failure: two first-time case reports and review of literature. Expert Opin Drug Metab Toxicol 14(4):379–385. https://doi.org/10.1080/17425255.2018.1461839 CrossRefPubMed

21.

Lea J, Greene T, Hebert L et al (2005) The relationship between magnitude of proteinuria reduction and risk of end-stage renal disease: results of the African American study of kidney disease and hypertension. Arch Intern Med 165(8):947–953. https://doi.org/10.1001/archinte.165.8.947 CrossRefPubMed

22.

Usui T, Kanda E, Iseki C et al (2018) Observation period for changes in proteinuria and risk prediction of end-stage renal disease in general population. Nephrology (Carlton) 23(9):821–829. https://doi.org/10.1111/nep.13093 CrossRef

23.

Capasso A, Benigni A, Capitanio U et al (2019) Summary of the international conference on onco-nephrology: an emerging field in medicine. Kidney Int 96(3):555–567. https://doi.org/10.1016/j.kint.2019.04.043 CrossRefPubMed

24.

Cosmai L, Porta C, Perazella MA et al (2018) Opening an onconephrology clinic: recommendations and basic requirements. Nephrol Dial Transplant 33(9):1503–1510. https://doi.org/10.1093/ndt/gfy188 CrossRefPubMed

25.

Brose MS, Nutting CM, Jarzab B, investigators D et al (2014) Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet 384(9940):319–328. https://doi.org/10.1016/S0140-6736(14)60421-9 CrossRefPubMedPubMedCentral

26.

Tatsugami K, Oya M, Kabu K et al (2018) Efficacy and safety of sorafenib for advanced renal cell carcinoma: real-world data of patients with renal impairment. Oncotarget 9(27):19406–19414. https://doi.org/10.18632/oncotarget.24779 CrossRefPubMedPubMedCentral

27.

Tatsugami K, Oya M, Kabu K et al (2018) Evaluation of efficacy and safety of sorafenib in kidney cancer patients aged 75 years and older: a propensity score-matched analysis. Br J Cancer 119(2):241–247. https://doi.org/10.1038/s41416-018-0129-3 CrossRefPubMedPubMedCentral

28.

Medina-Rosas J, Yap KS, Anderson M et al (2016) Utility of Urinary Protein-creatinine ratio and protein content in a 24-hour urine collection in systemic lupus erythematosus: a systematic review and meta-analysis. Arthritis Care Res (Hoboken) 68(9):1310–1319. https://doi.org/10.1002/acr.22828 CrossRef

29.

Singh R, Bhalla K, Nanda S et al (2019) Correlation of spot urinary protein: creatinine ratio and quantitative proteinuria in pediatric patients with nephrotic syndrome. J Family Med Prim Care 8(7):2343–2346. https://doi.org/10.4103/jfmpc.jfmpc_403_19 CrossRefPubMedPubMedCentral

30.

Akin D, Ozmen S (2019) An unresolved issue: the relationship between spot urine protein-to-creatinine ratio and 24-hour proteinuria. J Int Med Res 47(3):1179–1184. https://doi.org/10.1177/0300060518819602 CrossRefPubMedPubMedCentral

31.

Kobayashi S, Amano H, Terawaki H et al (2019) Spot urine protein/creatinine ratio as a reliable estimate of 24-hour proteinuria in patients with immunoglobulin A nephropathy, but not membranous nephropathy. BMC Nephrol 20(1):306. https://doi.org/10.1186/s12882-019-1486-8 CrossRefPubMedPubMedCentral

Title: Urinalysis by combination of the dipstick test and urine protein–creatinine ratio (UPCR) assessment can prevent unnecessary lenvatinib interruption in patients with thyroid cancer
Authors: Chie Masaki
Kiminori Sugino
Sakiko Kobayashi
Junko Akaishi
Kiyomi Y. Hames
Chisato Tomoda
Akifumi Suzuki
Kenichi Matsuzu
Takashi Uruno
Keiko Ohkuwa
Wataru Kitagawa
Mitsuji Nagahama
Koichi Ito
Publication date: 01-07-2020
Publisher: Springer Singapore
Keywords: Urinalysis
Lenvatinib
Thyroid Cancer
Thyroid Cancer
Thyroid Cancer
Published in: International Journal of Clinical Oncology / Issue 7/2020
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-020-01678-x

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Method

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 7/2020

Small-volume lymph node involvement and biochemical recurrence after robot-assisted radical prostatectomy with extended lymph node dissection in prostate cancer

Management and outcome of pediatric Wilms tumor with malignant inferior Vena cava thrombus: largest cohort of single-center experience

Clinical significance of thermal detection of soft-tissue tumors

Implementation of a molecular tumor board at a regional level to improve access to targeted therapy

Utility of whole brain radiation therapy for leptomeningeal carcinomatosis

Serum LOX-1 is a novel prognostic biomarker of colorectal cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer