A Phase I and Pharmacokinetic Study of Oral Lapatinib Administered Once or Twice Daily in Patients with Solid Malignancies

摘要: Purpose: This study determined the range of tolerable doses, clinical safety, pharmacokinetics, and preliminary evidence activity following once or twice daily administration lapatinib in patients with solid malignancies. Experimental Design: Cancer ( n = 81) received oral doses ranging from 175 to 1,800 mg 500 900 daily. Clinical assessments safety antitumor were recorded blood was sampled for pharmacokinetic assessments. The effect a low-fat meal on pharmacokinetics assessed subset patients. Results: Lapatinib well tolerated, such that dose escalation limited at only by pill burden. Twice-daily dosing implemented further explore tolerability, diarrhea most commonly reported adverse events once-daily (48%), nausea (40%), rash fatigue (38%) twice-daily (85%), (54%), (34%). serum concentrations accumulated upon repeated dosing, increasing nearly proportion dose, significantly increased when dosed food administered One patient head neck cancer achieved confirmed complete response 22 had stable disease ≥8 weeks including three >10 months (renal, lung, salivary gland cancers). Conclusion: tolerated administration. Systemic exposure dependent duration frequency prandial state. observed. (Clin Res 2009;15(21):6702–8)