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.
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 humanepidermal growth factor receptor 2-positive breast cancer. In a subset of patients, lack of tumorPTEN expression correlated with a shorter time to progression. CONCLUSION: In an unselected population, two schedules of lapatinib and vinorelbine were feasible and well tolerated.
Authors: Wei Yang; Sarah R Hosford; Lloye M Dillon; Kevin Shee; Stephanie C Liu; Jennifer R Bean; Laurent Salphati; Jodie Pang; Xiaolin Zhang; Michelle A Nannini; Eugene Demidenko; Darcy Bates; Lionel D Lewis; Jonathan D Marotti; Alan R Eastman; Todd W Miller Journal: Clin Cancer Res Date: 2016-01-05 Impact factor: 12.531
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Authors: E Brain; N Isambert; F Dalenc; V Diéras; J Bonneterre; K Rezai; M Jimenez; F Mefti-Lacheraf; E Cottura; P Tresca; L Vanlemmens; C Mahier-Aït Oukhatar; F Lokiec; P Fumoleau Journal: Br J Cancer Date: 2012-01-12 Impact factor: 7.640
Authors: Helen Kent Chew; Lee Schwartzberg; Suprith Badarinath; Peter Rubin; Grace Shumaker; James Daugherty; Michelle DeSilvio; Janine Mahoney Journal: Springerplus Date: 2014-02-22
Authors: Wolfgang Janni; Tomasz Sarosiek; Boguslawa Karaszewska; Joanna Pikiel; Elzbieta Staroslawska; Piotr Potemski; Christoph Salat; Etienne Brain; Christian Caglevic; Kathryn Briggs; Michelle Desilvio; Luca Marini; Christos Papadimitriou Journal: Breast Cancer Res Treat Date: 2014-01-09 Impact factor: 4.872
Authors: Qi Zhang; Ruichao Li; Xu Chen; Sang Beom Lee; Jing Pan; Donghai Xiong; Jiaqi Hu; Mark Steven Miller; Eva Szabo; Ronald A Lubet; Yian Wang; Ming You Journal: Oncotarget Date: 2017-08-02