Irinotecan-induced dysarthria: A case report and review of the literature

Ramirez, Krista G; Koch, Marla D; Edenfield, William J.

doi:10.1177/1078155216634181

Cited by 8 publications

(14 citation statements)

References 10 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is a potent chemotherapeutic agent, widely used in the treatment of solid tumors such as colorectal, lung, cervical, leukemia, and breast cancer. 8,9 It is an inhibitor of topoisomerase I (Topo-1) as it binds to DNA-Topo-I complex, generates a gap in DNA structure and therefore prevents DNA replication and ultimately leads to cell death. 10,11 Irinotecan alone or in combination with other drugs induces apoptosis through changes in expression of Bax, caspase-9, Bcl2, and surviving genes in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Effect of irinotecan on HMGB1, MMP9 expression, cell cycle, and cell growth in breast cancer (MCF-7) cells

et al. 2017

View full text Add to dashboard Cite

Irinotecan is a natural alkaloid agent widely used in cancer therapy. High-mobility group protein B1 as a non-histone chromosomal protein plays a fundamental role in gene expression and inflammation. In this study, the effect of irinotecan on high-mobility group protein B1 and MMP9 content, gene expression, cell cycle, and cell growth in human breast cancer cells (MCF-7) was investigated. The cells were exposed to various concentrations of irinotecan and the viability determined by trypan blue exclusion and 3-(4,5-dimethylthiazal-2-yl)-2,5-diphenyltetrazolium bromide assays. Highmobility group B proteins were extracted from the control and drug-treated cells and analyzed by immunoblot. Highmobility group protein B1 and MMP9 messenger RNA expression was studied by reverse transcription polymerase chain reaction. The results demonstrated reduction of cell viability upon increasing irinotecan concentration, up-regulated highmobility group protein B1 gene expression, and down-regulated MMP9 mRNA. Although the content of high-mobility group protein B1 was decreased in chromatin extract upon drug action, no high-mobility group protein B1 release to extracellular space was detected by immunoblot analysis. Irinotecan decreased H3K9 acetylation and increased poly ADP-ribose polymerase fragmentation to 89 kDa and anion superoxide production suggesting induction of apoptosis in these cells. Propidium iodide staining of the cells 24 h after the drug treatment revealed arrest of the cells in S-phase. From the results, it is concluded that overexpression of high-mobility group protein B1 in the presence of irinotecan precedes breast cancer cells into apoptosis and in this response the binding of irinotecan to chromatin or high-mobility group protein B1 may condense/aggregate chromatin, preventing high-mobility group protein B1 release from chromatin.

show abstract

Section: Introductionmentioning

confidence: 99%

Effect of irinotecan on HMGB1, MMP9 expression, cell cycle, and cell growth in breast cancer (MCF-7) cells

et al. 2017

View full text Add to dashboard Cite

show abstract

“…A range of time-to-onset of dysarthria has been reported in the literature from occurring shortly after start of infusion to several h after infusion [ 15 – 16 ]. Further, other cases described in the literature ranged from 15 min to 24 h in duration [ 4 , 17 , 18 ]. Of note, there is some heterogeneity in cases described in terms of diagnoses, with most cases occurring in metastatic colorectal carcinomas, as well as in doses and duration of initial infusion, ranging from 80 to 350 mg/m 2 and 30 to 120 min, respectively [ 4 , 15 – 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Based on this hypothesis, atropine would be a reasonable medical intervention; however, when administered at therapeutic doses, it has minimal effects on the central nervous systems [ 20 ]. Other agents such as scopolamine, with increased central nervous system activity, may have a role in managing irinotecan-induced dysarthria [ 18 ]. Further, predictive factors for the development of cholinergic syndrome, as determined by an ordered logistic regression analysis conducted by Kanbayashi et al, may shed light on predictive factors of this toxicity including female sex, and irinotecan dose ≥175 mg [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…In further support of the cholinergic hypothesis, patients described in the present study also experienced classical cholinergic symptoms including rhinitis, acute-onset diarrhea, and abdominal pain. One of the 3 patients in this study experienced diaphoresis, described by the patient as a “hot flash.” Known symptoms of cholinergic syndrome include rhinitis, hypersalivation, miosis, lacrimation, diaphoresis, flushing, diarrhea, and abdominal cramping [ 18 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Irinotecan-Associated Dysarthria in Patients with Pancreatic Cancer: A Single Site Experience

et al. 2020

View full text Add to dashboard Cite

“…MRI is commonly performed but rarely yields additional information. The measures described in the literature to alleviate this symptomatology are shown in Table 1 [8,9,11,[14][15][16][17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

Temporary Dysarthria Induced by Irinotecan-Case Report of This Rare Adverse Event

Landgraf¹,

Bognar²,

Guerra³

et al. 2017

JPP

View full text Add to dashboard Cite

Abstract:This report describes the case of a patient with dysarthria during the administration of the third cycle of Folfiri for the treatment of metastatic colon cancer. After a thorough neurological examination and neuroimaging, structural causes were excluded and thus the dysarthria was attributed to the irinotecan infusion. A slowing down of the infusion rate to 180 min during the 15 subsequent cycles led to the cessation of the episodes of dysarthria. In 2016, it was estimated there will be 134,490 new cases of colorectal cancer with a five-year survival rate of 21% among patients with metastatic disease. As Irinotecan is often part of the therapeutic regimen in such cases, both in the first and second-line setting, there is a need to report rare adverse outcomes in order to find out ways to better manage of these events. The mechanism by which Irinotecan causes dysarthria is unknown and further research in this area is warranted.

show abstract

Irinotecan-induced dysarthria: A case report and review of the literature

Cited by 8 publications

References 10 publications

Effect of irinotecan on HMGB1, MMP9 expression, cell cycle, and cell growth in breast cancer (MCF-7) cells

Effect of irinotecan on HMGB1, MMP9 expression, cell cycle, and cell growth in breast cancer (MCF-7) cells

Irinotecan-Associated Dysarthria in Patients with Pancreatic Cancer: A Single Site Experience

Temporary Dysarthria Induced by Irinotecan-Case Report of This Rare Adverse Event

Contact Info

Product

Resources

About