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Article: Phase I study of dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia

TitlePhase I study of dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia
Authors
Issue Date2008
PublisherBlackwell Publishing Japan. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CAS
Citation
Cancer Science, 2008, v. 99 n. 5, p. 1016-1020 How to Cite?
AbstractExtranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are rare, and their standard therapy has not been established. They are Epstein-Barr virus-associated lymphoid malignancies, and tumor cells express P-glycoprotein leading to multidrug resistance of the disease. Patients with stage IV, relapsed or refractory diseases have a dismal prognosis, with survival measured in months only. To develop an efficacious chemotherapeutic regimen, we conducted a dose-escalation feasibility study of a new chemotherapeutic regimen, SMILE, comprising the steroid dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide. The components of SMILE are multidrug resistance-unrelated agents and etoposide. Etoposide shows both in vitro and in vivo efficacy for Epstein-Barr virus-associated lymphoproliferative disorders. Eligible patients had newly diagnosed stage IV, relapsed or refractory diseases after first-line chemotherapy, were 15-69 years of age, and had satisfactory performance scores (0-2). Four dose levels of methotrexate and etoposide were originally planned to be evaluated. At level 1, six patients with extranodal NK/T-cell lymphoma, nasal type, were enrolled. Their disease status was newly diagnosed stage IV (n = 3), first relapse (n = 2), and primary refractory (n = 1). All of the first three patients developed dose-limiting toxicities, and one of them died of sepsis with grade 4 neutropenia. A protocol revision stipulating early granulocyte colony-stimulating factor administration was made. Two out of three additional patients developed dose-limiting toxicities that were all manageable and transient. For the six enrolled patients, the overall response rate was 67% and the complete response rate was 50%. Although its safety and efficacy require further evaluation, we recommend a SMILE chemotherapy dose level of 1 for further clinical studies. © 2008 Japanese Cancer Association.
Persistent Identifierhttp://hdl.handle.net/10722/77437
ISSN
2015 Impact Factor: 3.896
2015 SCImago Journal Rankings: 1.744
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYamaguchi, Men_HK
dc.contributor.authorSuzuki, Ren_HK
dc.contributor.authorKwong, YLen_HK
dc.contributor.authorKim, WSen_HK
dc.contributor.authorHasegawa, Yen_HK
dc.contributor.authorIzutsu, Ken_HK
dc.contributor.authorSuzumiya, Jen_HK
dc.contributor.authorOkamura, Ten_HK
dc.contributor.authorNakamura, Sen_HK
dc.contributor.authorKawa, Ken_HK
dc.contributor.authorOshimi, Ken_HK
dc.date.accessioned2010-09-06T07:31:53Z-
dc.date.available2010-09-06T07:31:53Z-
dc.date.issued2008en_HK
dc.identifier.citationCancer Science, 2008, v. 99 n. 5, p. 1016-1020en_HK
dc.identifier.issn1347-9032en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77437-
dc.description.abstractExtranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are rare, and their standard therapy has not been established. They are Epstein-Barr virus-associated lymphoid malignancies, and tumor cells express P-glycoprotein leading to multidrug resistance of the disease. Patients with stage IV, relapsed or refractory diseases have a dismal prognosis, with survival measured in months only. To develop an efficacious chemotherapeutic regimen, we conducted a dose-escalation feasibility study of a new chemotherapeutic regimen, SMILE, comprising the steroid dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide. The components of SMILE are multidrug resistance-unrelated agents and etoposide. Etoposide shows both in vitro and in vivo efficacy for Epstein-Barr virus-associated lymphoproliferative disorders. Eligible patients had newly diagnosed stage IV, relapsed or refractory diseases after first-line chemotherapy, were 15-69 years of age, and had satisfactory performance scores (0-2). Four dose levels of methotrexate and etoposide were originally planned to be evaluated. At level 1, six patients with extranodal NK/T-cell lymphoma, nasal type, were enrolled. Their disease status was newly diagnosed stage IV (n = 3), first relapse (n = 2), and primary refractory (n = 1). All of the first three patients developed dose-limiting toxicities, and one of them died of sepsis with grade 4 neutropenia. A protocol revision stipulating early granulocyte colony-stimulating factor administration was made. Two out of three additional patients developed dose-limiting toxicities that were all manageable and transient. For the six enrolled patients, the overall response rate was 67% and the complete response rate was 50%. Although its safety and efficacy require further evaluation, we recommend a SMILE chemotherapy dose level of 1 for further clinical studies. © 2008 Japanese Cancer Association.en_HK
dc.languageengen_HK
dc.publisherBlackwell Publishing Japan. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CASen_HK
dc.relation.ispartofCancer Scienceen_HK
dc.subject.meshAdolescenten_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols - administration & dosage - therapeutic useen_HK
dc.subject.meshAsparaginase - administration & dosage - therapeutic useen_HK
dc.subject.meshDexamethasone - administration & dosage - therapeutic useen_HK
dc.subject.meshEtoposide - administration & dosage - therapeutic useen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIfosfamide - administration & dosage - therapeutic useen_HK
dc.subject.meshLeukemia, Lymphoid - drug therapy - prevention & controlen_HK
dc.subject.meshLymphoma, Extranodal NK-T-Cell - drug therapy - prevention & controlen_HK
dc.subject.meshMethotrexate - administration & dosage - therapeutic useen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshRecurrenceen_HK
dc.titlePhase I study of dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemiaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1347-9032&volume=99&issue=5&spage=1016 &epage= 1020&date=2008&atitle=Phase+I+study+of+dexamethasone,+methotrexate,+ifosfamide,+l-asparaginase,+and+etoposide+(SMILE)+chemotherapy+for+advanced-stage,+relapsed+or+refractory+extranodal+natural+killer+(NK)/T-cell+lymphoma+and+leukemiaen_HK
dc.identifier.emailKwong, YL:ylkwong@hku.hken_HK
dc.identifier.authorityKwong, YL=rp00358en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1349-7006.2008.00768.xen_HK
dc.identifier.pmid18294294-
dc.identifier.scopuseid_2-s2.0-43649085643en_HK
dc.identifier.hkuros146505en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-43649085643&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume99en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1016en_HK
dc.identifier.epage1020en_HK
dc.identifier.isiWOS:000254609300027-
dc.publisher.placeJapanen_HK
dc.identifier.scopusauthoridYamaguchi, M=7404824526en_HK
dc.identifier.scopusauthoridSuzuki, R=35381312500en_HK
dc.identifier.scopusauthoridKwong, YL=7102818954en_HK
dc.identifier.scopusauthoridKim, WS=34975082200en_HK
dc.identifier.scopusauthoridHasegawa, Y=7403042454en_HK
dc.identifier.scopusauthoridIzutsu, K=7102942138en_HK
dc.identifier.scopusauthoridSuzumiya, J=7005666128en_HK
dc.identifier.scopusauthoridOkamura, T=7401572978en_HK
dc.identifier.scopusauthoridNakamura, S=35323670300en_HK
dc.identifier.scopusauthoridKawa, K=7005580914en_HK
dc.identifier.scopusauthoridOshimi, K=7006673135en_HK
dc.identifier.citeulike2631980-

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