Dysarthria induced by irinotecan in a patient with colorectal cancer

Lee, Kyung A.; Kang, Hee Won; Ahn, Ji Hyune; Suk, Hyoun Ju; Kim, Hyun-Ah

doi:10.2146/ajhp120542

Cited by 11 publications

(27 citation statements)

References 13 publications

(18 reference statements)

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“…The hypoglossal nerve plays an important role in speech since it innervates the muscles of the tongue and its overstimulation or damage can lead to the development of dysarthria. The density of cholinergic receptors in the brainstem nuclei is relatively high and the application of cholinergic agents results in an increase in the activity of the hypoglossal nerve [11]. Structural and neurological disorders should be ruled out first with the appropriate imaging, given that dysarthria may be a manifestation of injury to the central nervous system by edema, bleeding or metastatic disease which often require immediate intervention.…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…Dysarthria as a side effect of Irinotecan use was a rare event with few cases reported in the literature and even fewer cases described where an effective approach to this symptom was found [9,11]. Herein, we reported a patient with CRCm who presented with dysarthria, after excluding structural causes.…”

Section: David Publishingmentioning

confidence: 93%

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

Landgraf¹,

Bognar²,

Guerra³

et al. 2017

JPP

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Landgraf¹,

Bognar²,

Guerra³

et al. 2017

JPP

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“…With regard to the first point, since the approval of this regimen in Japan, it has been noted that FOLFIRINOX causes reversible dysarthria more often than previously reported for irinotecan monotherapy and other irinotecan-containing regimens (e.g., FOLFIRI and FOLFOXIRI) (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). In our hospital, overt speech disturbance diagnosed as dysarthria developed in 4 of the 9 patients (44.4%) who received FOLFIRINOX.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the unexpectedly high incidence of dysarthria appears to be a characteristic adverse effect of FOLFIRINOX that extends beyond ethnicity. Conversely, it is known that irinotecan directly causes dysarthria, although only 10 cases have been reported in the literature (2,3,(6)(7)(8)(9)(10)(11)(12)(13). Although irinotecan exerts its antitumor activity after being metabolized to SN-38 in vivo, dysarthria is apparently caused by the parent compound irinotecan binding to the active site of Table I.…”

Section: Discussionmentioning

confidence: 99%

FOLFIRINOX-induced reversible dysarthria: A case report and review of previous cases

et al. 2015

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Abstract. FOLFIRINOX is a standard chemotherapeutic regimen for patients with advanced pancreatic cancer who have a good performance status. In this study, we present the case of a 64-year-old male who developed dysarthria following FOLFIRINOX treatment, and review all four cases of dysarthria encountered among the nine patients who received this treatment in our hospital. In all cases, dysarthria occurred during the infusion of irinotecan in the first course of treatment, persisted for several hours, and then resolved rapidly without any sequelae. Physical and neurological examinations at the onset of dysarthria revealed no other abnormalities. Imaging studies revealed no abnormal findings. Atropine was prophylactically administered in the second and subsequent courses of treatment and effectively prevented or alleviated dysarthria. This acute neurological symptom is surprising and uncommon in traditional cancer chemotherapy, and medical oncologists may initially suspect the onset of stroke or cerebrovascular disease. However, consistent with our experience, all reported cases resolved completely, with no need for dose reduction or treatment interruption. IntroductionFOLFIRINOX, a combination chemotherapy regimen consisting of fluorouracil, leucovorin, irinotecan and oxaliplatin, is currently a standard treatment for patients with advanced pancreatic cancer who have a good performance status (1). However, FOLFIRINOX can cause severe toxicities, including neutropenia, febrile neutropenia, thrombocytopenia, fatigue and diarrhea, frequently requiring dose reduction or treatment interruption. Irinotecan itself rarely causes dysarthria, which is considered to be a type of acute cholinergic syndrome (2,3). Due to the notable discordance in the incidence of dysarthria between FOLFIRINOX and other irinotecan-containing regimens, we speculate that FOLFIRINOX-induced dysarthria is associated with the sequence of drug administration in this regimen (i.e., intravenous infusion of oxaliplatin, immediately followed by irinotecan). Since oxaliplatin is infused before irinotecan in FOLFIRINOX, oxaliplatin exaggerates the cholinergic effects of irinotecan, making dysarthria increasingly evident.In the present study we report a case of transient dysarthria, a speech disorder caused by disturbances of the muscles involved in speech, which occurred during the intravenous infusion of irinotecan as part of a FOLFIRINOX regimen in a 64-year-old male patient. We also review other cases previously observed in our hospital. The study was approved by the ethics committee of Nagoya University Hospital (Nagoya, Japan; approval no. 2014-0151). Case reportA 64-year-old Japanese male was referred to Nagoya University Hospital due to metastatic pancreatic cancer. The patient had a history of diabetes mellitus and was receiving an oral DPP4 inhibitor (Vildagliptin). He had no history of allergy or adverse reactions to specific drugs. He received FOLFIRINOX as first-line chemotherapy, which consisted of oxaliplatin 85 mg/m 2 administered intrave...

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Neurologic Symptoms as Adverse Drug Reactions

Jain

2021

Drug-Induced Neurological Disorders

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Dysarthria induced by irinotecan in a patient with colorectal cancer

Abstract: Irinotecan-induced dysarthria in a man being treated for colon cancer resolved with the discontinuation of irinotecan. With increases in the duration of infusion, the man received additional irinotecan treatments with no recurrence of dysarthria.

Cited by 11 publications

References 13 publications

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

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

FOLFIRINOX-induced reversible dysarthria: A case report and review of previous cases

Neurologic Symptoms as Adverse Drug Reactions

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