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

10 Citations (Scopus)

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

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Appointments and Schedules
Neoplasms
Poisons
Fatigue
Arm Bones
Febrile Neutropenia
Maximum Tolerated Dose
Leukopenia
vinorelbine
lapatinib
Combination Drug Therapy
Neutropenia
Epidermal Growth Factor Receptor
Diarrhea
Breast Neoplasms
Gene Expression
Pain
Mutation
Infection
Population

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Phase I study of continuous and intermittent schedules of lapatinib in combination with vinorelbine in solid tumors. / Chew, Helen K; Somlo, G.; Mack, Philip; Gitlitz, B.; Gandour-Edwards, Regina F; Christensen, Scott D; Linden, H.; Solis, L. J.; Yang, X.; Davies, A. M.

In: Annals of Oncology, Vol. 23, No. 4, 04.2012, p. 1023-1029.

Research output: Contribution to journalArticle

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AB - 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.

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