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Investigational New Drugs
Published in: Investigational New Drugs 6/2015

Open Access 01-12-2015 | PHASE I STUDIES

Phase I and pharmacological trial of lapatinib in combination with gemcitabine in patients with advanced breast cancer

Authors: R. van der Noll, W. M. Smit, A. N. M. Wymenga, D. S. Boss, M. Grob, A. D. R. Huitema, H. Rosing, M. M. Tibben, M. Keessen, H. Rehorst, J. H. Beijnen, J. H. M. Schellens

Published in: Investigational New Drugs | Issue 6/2015

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Summary

Background Lapatinib has proven efficacy as monotherapy and in combination with capecitabine in patients with metastatic breast cancer (MBC) overexpressing HER2 and/or EGFR. Gemcitabine also has anti-tumor activity in MBC and a favourable toxicity profile. In this phase I study lapatinib and gemcitabine were combined. Methods Female patients with advanced BC were given lapatinib once daily (QD) in 28-day cycles with gemcitabine administered on day 1, 8 and 15. Physical examinations, vital signs and blood sampling for hematology, clinical chemistry and pharmacokinetics (PK) and radiological assessments of disease were performed at regular intervals. Results In total, 33 patients were included. Six dose-limiting toxicities were observed, mostly grade 3 increases in liver function tests. Most common toxicities were fatigue (73 %), nausea (70 %), diarrhea (58 %), increases in ALAT and ASAT (55 and 52 %, respectively) and rash (46 %). The maximum tolerated dose was lapatinib 1250 mg QD with gemcitabine 1000 mg/m2. Lapatinib and gemcitabine PK did not appear to be influenced by each other. Anti-tumor activity was observed with one patient (4 %) showing complete response and six (23 %) partial response. Conclusion Despite a slightly increased toxicity profile compared to their respective monotherapies, lapatinib and gemcitabine can be safely combined while showing signs of anti-tumor activity.
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Metadata
Title
Phase I and pharmacological trial of lapatinib in combination with gemcitabine in patients with advanced breast cancer
Authors
R. van der Noll
W. M. Smit
A. N. M. Wymenga
D. S. Boss
M. Grob
A. D. R. Huitema
H. Rosing
M. M. Tibben
M. Keessen
H. Rehorst
J. H. Beijnen
J. H. M. Schellens
Publication date
01-12-2015
Publisher
Springer US
Published in
Investigational New Drugs / Issue 6/2015
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-015-0281-z

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