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Ann Oncol. 2009 Nov;20(11):1886-94. doi: 10.1093/annonc/mdp210. Epub 2009 Jul 1.

Response to imatinib plus sirolimus in advanced chordoma.

Author information

1
Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. silvia.stacchiotti@istitutotumori.mi.it

Abstract

BACKGROUND:

Imatinib (IM) is active in advanced chordoma. The evidence of upstream and/or downstream mammalian target of rapamycin (mTOR) pathway activation prompted us to combine an mTOR inhibitor, sirolimus, to IM in IM-resistant advanced chordoma.

PATIENTS AND METHODS:

Since July 2007, 10 progressive advanced chordoma patients with secondary resistance to IM, and biochemical and/or immunohistochemical evidence of upstream and/or downstream mTOR effector activation, started IM (400 mg/day) plus sirolimus (2 mg/day) on a named basis.

RESULTS:

The mean treatment duration was 9 months. Of nine patients assessable for response, at 3 months, we had one RECIST partial response (PR), seven stable disease (SD) and one progressive disease (PD). According to Choi criteria applied even to magnetic resonance imaging, we had seven PR (> or =10% decrease in size in four cases), one SD and one PD. Seven patients had a positron emission tomography response. The clinical benefit [RECIST complete response + PR + SD > or =6 months] was 89%. Pretreatment mTOR effectors analysis carried out in nine cases was positive in all patients (AKT activation in six patients, S6Sp6 expression/activation in seven). Post-treatment biopsy in one responsive patient confirmed S6 switch off.

CONCLUSION:

In addition to PDGFRB, mTOR pathway can be activated in chordomas and the combination of IM plus rapalogs may be effective in IM-resistant chordomas.

PMID:
19570961
DOI:
10.1093/annonc/mdp210
[Indexed for MEDLINE]

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