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

  • Chew H
  • Somlo G
  • Mack P
 et al. 
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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.

Author-supplied keywords

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

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  • H. K. Chew

  • G. Somlo

  • P. C. Mack

  • B. Gitlitz

  • R. Gandour-edwards

  • S. Christensen

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