A phase 2 study of temozolomide in pretreated metastatic colorectal cancer with MGMT promoter methylation

Maria Alessandra Calegari, A. Inno, S. Monterisi, Armando Orlandi, D. Santini, M. Basso, Alessandra Cassano, Maurizio Martini, Tonia Cenci, Ivana De Pascalis, Floriana Camarda, Brunella Barbaro, Luigi Maria Larocca, S. Gori, G. Tonini, Carlo Antonio Barone

Risultato della ricerca: Contributo in rivistaArticolo in rivista

25 Citazioni (Scopus)


Background: Presently, few options are available for refractory colorectal cancer (CRC). O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation is a frequent and early event in CRC tumourigenesis. This epigenetic silencing is a predictor of response to the alkylating drug temozolomide in glioblastoma. Preclinical evidences and some case reports showed temozolomide activity in CRC with MGMT silencing, but the available data from clinical trials are inconsistent. Methods: This was a multicentre, phase 2 trial, planned according to a two-stage Simon's optimal design to investigate activity and safety of temozolomide in refractory CRC harbouring MGMT promoter methylation. The primary end point was overall response rate (ORR). Patients who failed two or more prior treatments received temozolomide at a dose of 150-200 mg m -2 per day on days 1-5 every 28 days. Results: From July 2012 to June 2016, 225 patients were screened, 80 showed MGMT promoter methylation and 41 were enrolled. Overall response rate was 10% and disease control rate was 32%. Median progression-free survival and overall survival were 1.9 and 5.1 months, respectively. Conclusions: Temozolomide showed a modest activity in this heavily pretreated population and the study did not meet its primary end point. The role of temozolomide in CRC remains still controversial and further research is warranted.
Lingua originaleEnglish
pagine (da-a)1279-1286
Numero di pagine8
RivistaBritish Journal of Cancer
Stato di pubblicazionePubblicato - 2017


  • Aged
  • Aged, 80 and over
  • Anemia
  • Antineoplastic Agents, Alkylating
  • Colorectal Neoplasms
  • DNA Methylation
  • DNA Modification Methylases
  • DNA Repair Enzymes
  • Dacarbazine
  • Disease-Free Survival
  • Female
  • GTP Phosphohydrolases
  • Humans
  • MGMT
  • Membrane Proteins
  • Middle Aged
  • Mutation
  • Nausea
  • Neoplasm Metastasis
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • Retreatment
  • Survival Rate
  • Temozolomide
  • Thrombocytopenia
  • Treatment Outcome
  • Tumor Suppressor Proteins
  • Vomiting
  • colorectal cancer
  • metastatic
  • temozolomide


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