Breast Cancer Research and Treatment

, Volume 131, Issue 1, pp 111–116

Phase II trial of a novel capecitabine dosing schedule in combination with lapatinib for the treatment of patients with HER2-positive metastatic breast cancer

  • 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
Clinical trial

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 trastuzumab-refractory, HER2-positive, metastatic breast cancer (MBC). We performed this study to evaluate the activity and tolerability of capecitabine 7–7 with lapatinib in patients with trastuzumab-refractory MBC. Eligible patients had measurable, HER2-positive, MBC that progressed following exposure to trastuzumab. Treatment consisted of capecitabine 2,000 mg orally twice daily, 7–7 and lapatinib 1,250 mg orally daily. The primary endpoint was response rate. Secondary endpoints included toxicity, progression-free survival, and stable disease ≥6 months. Twenty-three 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 progression-free survival was 9.4 months. The most common treatment-related toxicities ≥ grade (gr) 2 were hand-foot 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 trastuzumab-refractory MBC.

Keywords

HER2-positive Capecitabine Lapatinib Breast cancer 

Supplementary material

10549_2011_1749_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 13 kb)

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Devika Gajria
    • 1
  • Joseph Gonzalez
    • 1
  • Kimberly Feigin
    • 2
  • Sujata Patil
    • 3
  • Carol Chen
    • 4
  • Maria Theodoulou
    • 1
  • Pamela Drullinsky
    • 1
  • Gabriella D’Andrea
    • 1
  • Diana Lake
    • 1
  • Larry Norton
    • 1
  • Clifford A. Hudis
    • 1
  • Tiffany A. Traina
    • 1
    • 5
  1. 1.Breast Cancer Medicine ServiceMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.RadiologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Epidemiology and BiostatisticsMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  4. 4.Cardiology ServiceMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  5. 5.Weill Medical College of Cornell UniversityNew YorkUSA

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