Phase I study of continuous and intermittent schedules of lapatinib in combination with vinorelbine in solid tumors

Helen K Chew, G. Somlo, Philip Mack, B. Gitlitz, Regina F Gandour-Edwards, Scott D Christensen, H. Linden, L. J. Solis, X. Yang, A. M. Davies

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: Chemotherapy in combination with small-molecule epidermal growth factor receptor inhibitors has yielded inconsistent results. Based on preclinical models, we conducted a phase I trial of two schedules of lapatinib and vinorelbine. Patient and methods: Patients had advanced solid tumors and up to two prior chemotherapeutic regimens. Patients were enrolled on two dose-escalating schedules of lapatinib, continuous (arm A) or intermittent (arm B), with vinorelbine on days 1, 8, and 15 of a 28-day cycle. Tumors from a subset of patients were evaluated for gene mutations and expression of targets of interest. Results: Fifty-one patients were treated. The most common grade 3/4 toxic effects included leukopenia, neutropenia, and fatigue. Dose-limiting toxic effects were grade 3 infection, febrile neutropenia, and diarrhea (arm A) and bone pain and fatigue (arm B). The maximum tolerated dose was vinorelbine 20 mg/m 2 weekly and lapatinib 1500 mg daily (arm A) and vinorelbine 25 mg/m 2 weekly and lapatinib 1500 mg intermittently (arm B). One patient on each arm had a complete response; both had human epidermal growth factor receptor 2-positive breast cancer. In a subset of patients, lack of tumor PTEN expression correlated with a shorter time to progression. Conclusion: In an unselected population, two schedules of lapatinib and vinorelbine were feasible and well tolerated.

Original languageEnglish (US)
Pages (from-to)1023-1029
Number of pages7
JournalAnnals of Oncology
Volume23
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • EGFR (epidermal growth factor receptor)
  • HER2
  • Lapatinib
  • PTEN
  • Vinorelbine

ASJC Scopus subject areas

  • Oncology
  • Hematology

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