| Title | Response to imatinib plus sirolimus in advanced chordoma. | | Author(s) | Stacchiotti S, Marrari A, Tamborini E, Palassini E, Virdis E, Messina A, Crippa F, Morosi C, Gronchi A, Pilotti S, Casali PG | | Institution | Department of Cancer Medicine. | | Source | Ann Oncol 2009 Jul 1. | | 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 (>/=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 >/=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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19570961 |
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