Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors may have efficacy as an intervention for advanced malignancies. Oral ulceration (OU), reported as mucositis, has been a dose‐limiting toxicity for this new class of agents. An analysis of the appearance, course, and toxicity associations of...
Gespeichert in:
| Veröffentlicht in: | Cancer 2010-01, Vol.116 (1), p.210-215 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 215 |
|---|---|
| container_issue | 1 |
| container_start_page | 210 |
| container_title | Cancer |
| container_volume | 116 |
| creator | Sonis, Stephen Treister, Nathaniel Chawla, Sant Demetri, George Haluska, Frank |
| description | BACKGROUND:
Mammalian target of rapamycin (mTOR) inhibitors may have efficacy as an intervention for advanced malignancies. Oral ulceration (OU), reported as mucositis, has been a dose‐limiting toxicity for this new class of agents. An analysis of the appearance, course, and toxicity associations of mTOR inhibitor‐associated stomatitis (mIAS) demonstrated that the condition is distinct from conventional mucositis (CM) and more closely resembles aphthous stomatitis.
METHODS:
Safety data from 78 solid tumor patients enrolled in 2 Phase 1, multicenter trials of the mTOR inhibitor deforolimus (AP23573, MK‐8669) were evaluated. Adverse events (AEs) based on National Cancer Institute Common Toxicity Criteria for National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0) criteria were coded, consolidated, and stratified according to the presence or absence and duration of concordant OU. The relation between OU and other AEs was analyzed.
RESULTS:
Treatment‐emergent AEs were reported in 91% of 78 study participants. OUs were reported in 66%, appeared within 5 days of deforolimus administration, and were discrete, ovoid, superficial, well demarcated, and surrounded by an erythematous halo. Their clinical appearance and distribution were similar to that of aphthous stomatitis but inconsistent with CM. Patients with OU were more likely to have nonspecific rashes and acneiform dermatitis but not gastrointestinal AEs.
CONCLUSIONS:
OU associated with mTOR inhibitor therapy differed from CM. Lesions more closely resembled those of aphthous stomatitis. The lack of other gastrointestinal involvement but the presence of a higher incidence of concomitant cutaneous AEs provided additional evidence to suggest a distinction between mIAS and CM. Treatment strategies for aphthous stomatitis may be a rational approach for the prevention and control of mIAS. Cancer 2010. © 2010 American Cancer Society.
Mammalian target of rapamycin inhibitor‐associated stomatitis (mIAS) differed in behavior, appearance, and associated toxicities from mucositis induced by cytotoxic chemotherapy. The results from this study indicated that the similarity between mIAS and aphthous stomatitis may be the basis for an effective approach to its prevention and treatment. |
| doi_str_mv | 10.1002/cncr.24696 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1002_cncr_24696</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>CNCR24696</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3946-c6c08fd09b4743d24ea1cedc2c0638512a3656b680be727b94a5a2b5ec84dc0b3</originalsourceid><addsrcrecordid>eNp90EtLxDAQB_AgiruuXvwAkosXoWteTdujFF8gKqLgrUynqRvpi6SyrH55W7vozdMww48Z5k_IMWdLzpg4xwbdUiid6B0y5yyJAsaV2CVzxlgchEq-zsiB9-9DG4lQ7pMZT2ItYh7NydejM5WtbQNuQ3EFDrA3zn5Cb9uGtiVtHVS0Mn5oPQXvW7TQm4Kubb-itlnZ3Pat8yOtoa6hstDQHtyb6ceZgw7qDdpmsBShQeNoNyw3Te8PyV4JlTdH27ogL1eXz-lNcPdwfZte3AUoE6UD1MjismBJriIlC6EMcDQFCmRaxiEXIHWocx2z3EQiyhMFIYg8NBirAlkuF-Rs2ouu9d6ZMuucrYeHM86yMcFsTDD7SXDAJxPuPvLaFH90G9kATrcAPEJVuuEp63-dEFJIFY2OT25tK7P552SW3qdP0_FvtTuMFA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients</title><source>MEDLINE</source><source>Wiley Free Content</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library All Journals</source><source>Alma/SFX Local Collection</source><creator>Sonis, Stephen ; Treister, Nathaniel ; Chawla, Sant ; Demetri, George ; Haluska, Frank</creator><creatorcontrib>Sonis, Stephen ; Treister, Nathaniel ; Chawla, Sant ; Demetri, George ; Haluska, Frank</creatorcontrib><description>BACKGROUND:
Mammalian target of rapamycin (mTOR) inhibitors may have efficacy as an intervention for advanced malignancies. Oral ulceration (OU), reported as mucositis, has been a dose‐limiting toxicity for this new class of agents. An analysis of the appearance, course, and toxicity associations of mTOR inhibitor‐associated stomatitis (mIAS) demonstrated that the condition is distinct from conventional mucositis (CM) and more closely resembles aphthous stomatitis.
METHODS:
Safety data from 78 solid tumor patients enrolled in 2 Phase 1, multicenter trials of the mTOR inhibitor deforolimus (AP23573, MK‐8669) were evaluated. Adverse events (AEs) based on National Cancer Institute Common Toxicity Criteria for National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0) criteria were coded, consolidated, and stratified according to the presence or absence and duration of concordant OU. The relation between OU and other AEs was analyzed.
RESULTS:
Treatment‐emergent AEs were reported in 91% of 78 study participants. OUs were reported in 66%, appeared within 5 days of deforolimus administration, and were discrete, ovoid, superficial, well demarcated, and surrounded by an erythematous halo. Their clinical appearance and distribution were similar to that of aphthous stomatitis but inconsistent with CM. Patients with OU were more likely to have nonspecific rashes and acneiform dermatitis but not gastrointestinal AEs.
CONCLUSIONS:
OU associated with mTOR inhibitor therapy differed from CM. Lesions more closely resembled those of aphthous stomatitis. The lack of other gastrointestinal involvement but the presence of a higher incidence of concomitant cutaneous AEs provided additional evidence to suggest a distinction between mIAS and CM. Treatment strategies for aphthous stomatitis may be a rational approach for the prevention and control of mIAS. Cancer 2010. © 2010 American Cancer Society.
Mammalian target of rapamycin inhibitor‐associated stomatitis (mIAS) differed in behavior, appearance, and associated toxicities from mucositis induced by cytotoxic chemotherapy. The results from this study indicated that the similarity between mIAS and aphthous stomatitis may be the basis for an effective approach to its prevention and treatment.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/cncr.24696</identifier><identifier>PMID: 19862817</identifier><identifier>CODEN: CANCAR</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Aged ; Antineoplastic Agents - adverse effects ; aphthous stomatitis ; Biological and medical sciences ; cancer ; Clinical Trials, Phase I as Topic ; Facial bones, jaws, teeth, parodontium: diseases, semeiology ; Female ; Humans ; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors ; Male ; mammalian target of rapamycin inhibitor ; Medical sciences ; Middle Aged ; mucositis ; Mucositis - chemically induced ; Neoplasms - drug therapy ; Non tumoral diseases ; Otorhinolaryngology. Stomatology ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Sirolimus - adverse effects ; Sirolimus - analogs & derivatives ; Stomatitis - chemically induced ; TOR Serine-Threonine Kinases ; Tumors</subject><ispartof>Cancer, 2010-01, Vol.116 (1), p.210-215</ispartof><rights>Copyright © 2010 American Cancer Society</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2010 American Cancer Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3946-c6c08fd09b4743d24ea1cedc2c0638512a3656b680be727b94a5a2b5ec84dc0b3</citedby><cites>FETCH-LOGICAL-c3946-c6c08fd09b4743d24ea1cedc2c0638512a3656b680be727b94a5a2b5ec84dc0b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcncr.24696$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcncr.24696$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,4023,27922,27923,27924,45573,45574,46408,46832</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22323477$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19862817$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sonis, Stephen</creatorcontrib><creatorcontrib>Treister, Nathaniel</creatorcontrib><creatorcontrib>Chawla, Sant</creatorcontrib><creatorcontrib>Demetri, George</creatorcontrib><creatorcontrib>Haluska, Frank</creatorcontrib><title>Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients</title><title>Cancer</title><addtitle>Cancer</addtitle><description>BACKGROUND:
Mammalian target of rapamycin (mTOR) inhibitors may have efficacy as an intervention for advanced malignancies. Oral ulceration (OU), reported as mucositis, has been a dose‐limiting toxicity for this new class of agents. An analysis of the appearance, course, and toxicity associations of mTOR inhibitor‐associated stomatitis (mIAS) demonstrated that the condition is distinct from conventional mucositis (CM) and more closely resembles aphthous stomatitis.
METHODS:
Safety data from 78 solid tumor patients enrolled in 2 Phase 1, multicenter trials of the mTOR inhibitor deforolimus (AP23573, MK‐8669) were evaluated. Adverse events (AEs) based on National Cancer Institute Common Toxicity Criteria for National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0) criteria were coded, consolidated, and stratified according to the presence or absence and duration of concordant OU. The relation between OU and other AEs was analyzed.
RESULTS:
Treatment‐emergent AEs were reported in 91% of 78 study participants. OUs were reported in 66%, appeared within 5 days of deforolimus administration, and were discrete, ovoid, superficial, well demarcated, and surrounded by an erythematous halo. Their clinical appearance and distribution were similar to that of aphthous stomatitis but inconsistent with CM. Patients with OU were more likely to have nonspecific rashes and acneiform dermatitis but not gastrointestinal AEs.
CONCLUSIONS:
OU associated with mTOR inhibitor therapy differed from CM. Lesions more closely resembled those of aphthous stomatitis. The lack of other gastrointestinal involvement but the presence of a higher incidence of concomitant cutaneous AEs provided additional evidence to suggest a distinction between mIAS and CM. Treatment strategies for aphthous stomatitis may be a rational approach for the prevention and control of mIAS. Cancer 2010. © 2010 American Cancer Society.
Mammalian target of rapamycin inhibitor‐associated stomatitis (mIAS) differed in behavior, appearance, and associated toxicities from mucositis induced by cytotoxic chemotherapy. The results from this study indicated that the similarity between mIAS and aphthous stomatitis may be the basis for an effective approach to its prevention and treatment.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>aphthous stomatitis</subject><subject>Biological and medical sciences</subject><subject>cancer</subject><subject>Clinical Trials, Phase I as Topic</subject><subject>Facial bones, jaws, teeth, parodontium: diseases, semeiology</subject><subject>Female</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins - antagonists & inhibitors</subject><subject>Male</subject><subject>mammalian target of rapamycin inhibitor</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>mucositis</subject><subject>Mucositis - chemically induced</subject><subject>Neoplasms - drug therapy</subject><subject>Non tumoral diseases</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Sirolimus - adverse effects</subject><subject>Sirolimus - analogs & derivatives</subject><subject>Stomatitis - chemically induced</subject><subject>TOR Serine-Threonine Kinases</subject><subject>Tumors</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90EtLxDAQB_AgiruuXvwAkosXoWteTdujFF8gKqLgrUynqRvpi6SyrH55W7vozdMww48Z5k_IMWdLzpg4xwbdUiid6B0y5yyJAsaV2CVzxlgchEq-zsiB9-9DG4lQ7pMZT2ItYh7NydejM5WtbQNuQ3EFDrA3zn5Cb9uGtiVtHVS0Mn5oPQXvW7TQm4Kubb-itlnZ3Pat8yOtoa6hstDQHtyb6ceZgw7qDdpmsBShQeNoNyw3Te8PyV4JlTdH27ogL1eXz-lNcPdwfZte3AUoE6UD1MjismBJriIlC6EMcDQFCmRaxiEXIHWocx2z3EQiyhMFIYg8NBirAlkuF-Rs2ouu9d6ZMuucrYeHM86yMcFsTDD7SXDAJxPuPvLaFH90G9kATrcAPEJVuuEp63-dEFJIFY2OT25tK7P552SW3qdP0_FvtTuMFA</recordid><startdate>20100101</startdate><enddate>20100101</enddate><creator>Sonis, Stephen</creator><creator>Treister, Nathaniel</creator><creator>Chawla, Sant</creator><creator>Demetri, George</creator><creator>Haluska, Frank</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20100101</creationdate><title>Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients</title><author>Sonis, Stephen ; Treister, Nathaniel ; Chawla, Sant ; Demetri, George ; Haluska, Frank</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3946-c6c08fd09b4743d24ea1cedc2c0638512a3656b680be727b94a5a2b5ec84dc0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>aphthous stomatitis</topic><topic>Biological and medical sciences</topic><topic>cancer</topic><topic>Clinical Trials, Phase I as Topic</topic><topic>Facial bones, jaws, teeth, parodontium: diseases, semeiology</topic><topic>Female</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins - antagonists & inhibitors</topic><topic>Male</topic><topic>mammalian target of rapamycin inhibitor</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>mucositis</topic><topic>Mucositis - chemically induced</topic><topic>Neoplasms - drug therapy</topic><topic>Non tumoral diseases</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Sirolimus - adverse effects</topic><topic>Sirolimus - analogs & derivatives</topic><topic>Stomatitis - chemically induced</topic><topic>TOR Serine-Threonine Kinases</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sonis, Stephen</creatorcontrib><creatorcontrib>Treister, Nathaniel</creatorcontrib><creatorcontrib>Chawla, Sant</creatorcontrib><creatorcontrib>Demetri, George</creatorcontrib><creatorcontrib>Haluska, Frank</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sonis, Stephen</au><au>Treister, Nathaniel</au><au>Chawla, Sant</au><au>Demetri, George</au><au>Haluska, Frank</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients</atitle><jtitle>Cancer</jtitle><addtitle>Cancer</addtitle><date>2010-01-01</date><risdate>2010</risdate><volume>116</volume><issue>1</issue><spage>210</spage><epage>215</epage><pages>210-215</pages><issn>0008-543X</issn><eissn>1097-0142</eissn><coden>CANCAR</coden><abstract>BACKGROUND:
Mammalian target of rapamycin (mTOR) inhibitors may have efficacy as an intervention for advanced malignancies. Oral ulceration (OU), reported as mucositis, has been a dose‐limiting toxicity for this new class of agents. An analysis of the appearance, course, and toxicity associations of mTOR inhibitor‐associated stomatitis (mIAS) demonstrated that the condition is distinct from conventional mucositis (CM) and more closely resembles aphthous stomatitis.
METHODS:
Safety data from 78 solid tumor patients enrolled in 2 Phase 1, multicenter trials of the mTOR inhibitor deforolimus (AP23573, MK‐8669) were evaluated. Adverse events (AEs) based on National Cancer Institute Common Toxicity Criteria for National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0) criteria were coded, consolidated, and stratified according to the presence or absence and duration of concordant OU. The relation between OU and other AEs was analyzed.
RESULTS:
Treatment‐emergent AEs were reported in 91% of 78 study participants. OUs were reported in 66%, appeared within 5 days of deforolimus administration, and were discrete, ovoid, superficial, well demarcated, and surrounded by an erythematous halo. Their clinical appearance and distribution were similar to that of aphthous stomatitis but inconsistent with CM. Patients with OU were more likely to have nonspecific rashes and acneiform dermatitis but not gastrointestinal AEs.
CONCLUSIONS:
OU associated with mTOR inhibitor therapy differed from CM. Lesions more closely resembled those of aphthous stomatitis. The lack of other gastrointestinal involvement but the presence of a higher incidence of concomitant cutaneous AEs provided additional evidence to suggest a distinction between mIAS and CM. Treatment strategies for aphthous stomatitis may be a rational approach for the prevention and control of mIAS. Cancer 2010. © 2010 American Cancer Society.
Mammalian target of rapamycin inhibitor‐associated stomatitis (mIAS) differed in behavior, appearance, and associated toxicities from mucositis induced by cytotoxic chemotherapy. The results from this study indicated that the similarity between mIAS and aphthous stomatitis may be the basis for an effective approach to its prevention and treatment.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19862817</pmid><doi>10.1002/cncr.24696</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-543X |
| ispartof | Cancer, 2010-01, Vol.116 (1), p.210-215 |
| issn | 0008-543X 1097-0142 |
| language | eng |
| recordid | cdi_crossref_primary_10_1002_cncr_24696 |
| source | MEDLINE; Wiley Free Content; EZB-FREE-00999 freely available EZB journals; Wiley Online Library All Journals; Alma/SFX Local Collection |
| subjects | Adult Aged Antineoplastic Agents - adverse effects aphthous stomatitis Biological and medical sciences cancer Clinical Trials, Phase I as Topic Facial bones, jaws, teeth, parodontium: diseases, semeiology Female Humans Intracellular Signaling Peptides and Proteins - antagonists & inhibitors Male mammalian target of rapamycin inhibitor Medical sciences Middle Aged mucositis Mucositis - chemically induced Neoplasms - drug therapy Non tumoral diseases Otorhinolaryngology. Stomatology Protein-Serine-Threonine Kinases - antagonists & inhibitors Sirolimus - adverse effects Sirolimus - analogs & derivatives Stomatitis - chemically induced TOR Serine-Threonine Kinases Tumors |
| title | Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T22%3A27%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-wiley_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Preliminary%20characterization%20of%20oral%20lesions%20associated%20with%20inhibitors%20of%20mammalian%20target%20of%20rapamycin%20in%20cancer%20patients&rft.jtitle=Cancer&rft.au=Sonis,%20Stephen&rft.date=2010-01-01&rft.volume=116&rft.issue=1&rft.spage=210&rft.epage=215&rft.pages=210-215&rft.issn=0008-543X&rft.eissn=1097-0142&rft.coden=CANCAR&rft_id=info:doi/10.1002/cncr.24696&rft_dat=%3Cwiley_cross%3ECNCR24696%3C/wiley_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/19862817&rfr_iscdi=true |