Authors: Devika Gajria Joseph Gonzalez Kimberly Feigin Sujata Patil Carol Chen Maria Theodoulou Pamela Drullinsky Gabriella D’Andrea Diana Lake Larry Norton Clifford A Hudis Tiffany A Traina
Publish Date: 2011/09/04
Volume: 131, Issue: 1, Pages: 111-116
Abstract
Our group applied mathematical modeling to capecitabine dosing and predicted 7 days of treatment followed by 7 days of rest 7–7 would improve efficacy and minimize toxicity The conventional schedule of capecitabine limits full dosing in combination with other agents due to toxicity Lapatinib inhibits the tyrosine kinase of HER2 and has activity when added to conventionally scheduled capecitabine for the treatment of patients with trastuzumabrefractory HER2positive metastatic breast cancer MBC We performed this study to evaluate the activity and tolerability of capecitabine 7–7 with lapatinib in patients with trastuzumabrefractory MBC Eligible patients had measurable HER2positive MBC that progressed following exposure to trastuzumab Treatment consisted of capecitabine 2000 mg orally twice daily 7–7 and lapatinib 1250 mg orally daily The primary endpoint was response rate Secondary endpoints included toxicity progressionfree survival and stable disease ≥6 months Twentythree patients were treated on study More than 60 had prior chemotherapy for MBC and all had prior trastuzumab After a median of 23 weeks range 2–96+ five patients had partial responses 23 95 CI 7–44 and six 27 95 CI 10–48 had stable disease ≥6 months Median progressionfree survival was 94 months The most common treatmentrelated toxicities ≥ grade gr 2 were handfoot syndrome gr 2 43 gr 3 4 gr 4 0 diarrhea gr 2 26 gr 3/4 0 elevated liver chemistries gr 2 17 gr 3/4 0 and anemia gr 2 13 gr 3 4 gr 4 4 No grade ≥3 nausea vomiting or diarrhea events occurred This study demonstrated feasibility and after meeting biostatistical requirements for continued accrual was terminated in anticipation of slow enrollment Capecitabine 7–7 with lapatinib was well tolerated with minimal gastrointestinal toxicity Antitumor activity was observed in patients with trastuzumabrefractory MBCPresented in part at the Annual Meeting American Society Clinical Oncology May 30June 3 2009 Orlando FL 32nd Annual San Antonio Breast Cancer Symposium December 9–13 2009 San Antonio TX and the 33rd Annual San Antonio Breast Cancer Symposium December 8–12 2010 San Antonio TX
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