A phase I/II trial of GW572016 (lapatinib) in recurrent glioblastoma multiforme: clinical outcomes, pharmacokinetics and molecular correlation

摘要: We undertook a phase I/II study of the EGFR/erbB2 inhibitor lapatinib in patients with recurrent glioblastoma multiforme (GBM) to determine response rate, pharmacokinetics (PK) and recommended dose taking enzyme-inducing anti-epileptic drugs (EIAEDs) explore relationships molecular genetics outcome. Recurrent GBM EIAEDs were enrolled on I portion (starting 1,000 mg po bid). In absence dose-limiting toxicity (DLT), escalation continued cohorts three patients. Patients not II arm (lapatinib 750 mg bid po). Immunohistochemical quantitative RT PCR studies performed tumor PTEN EGFRvIII status, respectively. Lapatinib PK was analyzed using HPLC tandem mass spectrometry. Phase II: Of 17 patients, 4 had stable disease 13 progressed. Accrual ceased because no responses. I: Four received three, 1,500 mg bid. No DLT occurred, but stopped lack efficacy. apparent oral clearance 106.9 L h−1 m−2 comparison 12.1 L h−1 m−2 those EIAEDs. 16 loss seen 6 expression 4. correlation outcome results. increased by approximately tenfold when given this small sample, did predict favorable subtype. Overall, show significant activity