Related Experiment Video
Updated: May 30, 2026
Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3
Published on: April 7, 2023
Phase I study of continuous and intermittent schedules of lapatinib in combination with vinorelbine in solid tumors
1Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, USA. helen.chew@ucdmc.ucdavis.edu
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.
