Dose-Dense Temozolomide in Patients with MGMT-Silenced Chemorefractory Colorectal Cancer.
Background: In a phase II study, we showed that temozolomide (TMZ) was tolerable and active in heavily pre-treated patients with advanced colorectal cancer (CRC) and MGMT methylation. A schedule of dose-dense TMZ may have enhanced activity due to the higher cumulative dose and induction of MGMT depl...
| Publicado en: | Targeted Oncology Vol. 11; no. 3; pp. 337 - 344 |
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| Autores principales: | , , , , , , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Springer Nature
Jun2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=116037752&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 116037752 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 17762596 47DQ jtl: Targeted Oncology issn: 17762596 maglogo: N pubinfo: dt: Jun2016 vid: 11 iid: 3 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 116037752 116037752 NLM26538496 116037752 10.1007/s11523-015-0397-2 NLM26538496 116037752 ppf: 337 ppct: 7 formats: fmt: @attributes: type: P tig: atl: Dose-Dense Temozolomide in Patients with MGMT-Silenced Chemorefractory Colorectal Cancer. aug: au: Pietrantonio, Filippo de Braud, Filippo Milione, Massimo Maggi, Claudia Iacovelli, Roberto Dotti, Katia Perrone, Federica Tamborini, Elena Caporale, Marta Berenato, Rosa Leone, Giorgia Pellegrinelli, Alessio Bossi, Ilaria Festinese, Fabrizio Federici, Stefano Di Bartolomeo, Maria Dotti, Katia Fiorella affil: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1 - 20133 Milan Italy sug: subj: Colorectal Neoplasms Drug Therapy Antineoplastic Agents, Alkylating Therapeutic Use Dacarbazine Analogs and Derivatives Dacarbazine Administration and Dosage Aged Antineoplastic Agents, Alkylating Pharmacodynamics Antineoplastic Agents, Alkylating Administration and Dosage Dacarbazine Pharmacodynamics Adult Aged, 80 and Over Colorectal Neoplasms Pathology Dacarbazine Therapeutic Use Middle Age Human Aged: 65+ years Adult: 19-44 years Aged, 80 & over Middle Aged: 45-64 years ab: Background: In a phase II study, we showed that temozolomide (TMZ) was tolerable and active in heavily pre-treated patients with advanced colorectal cancer (CRC) and MGMT methylation. A schedule of dose-dense TMZ may have enhanced activity due to the higher cumulative dose and induction of MGMT depletion, even in resistant tumors.Methods: Thirty-two patients with chemorefractory MGMT-methylated CRC were treated with TMZ at a daily dose of 75 mg/m(2) for 21 consecutive days every 4 weeks, for up to six cycles or until the occurrence of progressive disease/unacceptable toxicity. The primary endpoint was treatment activity in terms of objective response rate (ORR). MGMT protein expression was tested by immunohistochemistry (IHC) on two pooled cohorts: patients from the previous study of standard-dose TMZ and those from the current investigation.Results: From November 2013 to December 2014, 32 patients were treated at Fondazione IRCCS Istituto Nazionale dei Tumori. We observed only three episodes of grade 3 asthenia and no significant myelotoxicity. The ORR was 16 % (all partial responses occurring in RAS-BRAF-mutated tumors). Median progression-free survival (PFS) and overall survival (OS) were 2.3 and 6.7 months, respectively. Patients with MGMT-low expression by IHC had a significantly higher ORR (p < 0.0001) and PFS (p = 0.001) compared to those with MGMT-high expression, while no difference was observed in OS.Conclusions: Our data confirm the encouraging activity of TMZ in chemorefractory CRC patients selected for MGMT silencing, even in the RAS-BRAF-mutated population. The role of MGMT IHC as a biomarker for improving patient selection warrants further prospective confirmation. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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