Academic Journal
Gene expression profile predicts response to the combination of tosedostat and low-dose cytarabine in elderly AML
| العنوان: | Gene expression profile predicts response to the combination of tosedostat and low-dose cytarabine in elderly AML |
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| المؤلفون: | Visani G., Loscocco F., Dennis M., Zuffa E., Candoni A., Sensi A., Giannini B., Musuraca G., Mianulli A. M., Clavio M., Rocchi M., Gibellini D., Navari M., Gilkes A., Piccaluga P. P., Isidori A. |
| المساهمون: | Visani, G., Loscocco, F., Dennis, M., Zuffa, E., Candoni, A., Sensi, A., Giannini, B., Musuraca, G., Mianulli, A. M., Clavio, M., Rocchi, M., Gibellini, D., Navari, M., Gilkes, A., Piccaluga, P. P., Isidori, A. |
| سنة النشر: | 2020 |
| المجموعة: | Archivio della ricerca dell'Università di Modena e Reggio Emilia (Unimore: IRIS) |
| الوصف: | Tosedostat is an orally administered metalloenzyme inhibitor with antiproliferative and antiangiogenic activity against hematological and solid human cancers. Clinical activity has been demonstrated in relapsed acutemyeloid leukemia (AML). Thirty-three elderly patients with AML (median age, 75 years) received 120mgtosedostat orally once daily combinedwith subcutaneous low-dose cytarabine (20 mg twice per day for 10 days, up to 8 cycles), until disease progression. Inductionmortality was 12%. According to an intention-to-treat analysis, the complete remission (CR) rate was 48.5%, and thus the primary end point of the study was reached (expected CR, 25%). The partial remission rate was 6.1%,with an overall response rate of 54.5%. Furthermore, 4 of 33 patients had stable disease (median: 286 days). Themedian progression-free survival and overall survival (OS)were 203 days and 222 days, respectively. Responding patients had a longer median OS than nonresponding patients (P=.001). Amicroarray analysis performed in 29 of 33 patients identified 188 genes associated with clinical response (CR vs no CR). Three of them (CD93, GORASP1, CXCL16) were validated by quantitative polymerase chain reaction, which correctly classified 83% of the patients. Specifically, CR achievement was efficiently predicted by the gene expression patterns, with an overall accuracy exceeding 90%. Finally, a negative predictive value of 100% was validated in an independent series, thus representing the first molecular predictor for clinical response to a specific combination drug treatment for AML. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/33075137; info:eu-repo/semantics/altIdentifier/wos/WOS:000582796200008; volume:4; issue:20; firstpage:5040; lastpage:5049; journal:BLOOD ADVANCES; https://hdl.handle.net/11380/1294008; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85096186992 |
| DOI: | 10.1182/BLOODADVANCES.2020002305 |
| الاتاحة: | https://hdl.handle.net/11380/1294008 https://doi.org/10.1182/BLOODADVANCES.2020002305 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.505E3F07 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1182/BLOODADVANCES.2020002305 |
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