An European Organisation for Research and Treatment of Cancer phase I study of lapatinib and docetaxel as neoadjuvant treatment for Human Epidermal Growth Factor Receptor 2 (HER2) positive locally-advanced/inflammatory or large operable breast cancer

Our recommended dose for phase II is lapatinib 1000 mg/day and docetaxel 100 mg/m2 with G-CSF in HER2 positive non-metastatic breast cancer. The dose of lapatinib should have been 1250 mg/day but we were mindful of the high rate of treatment discontinuation in GeparQuinto with lapatinib 1250 mg/day combined with docetaxel. No grade 3-4 diarrhoea was observed. Pharmacodynamics analysis suggests that concomitant medications altering P-glycoprotein activity (in addition to lapatinib) can modify toxicity, including non-haematological toxicities. This needs verification in larger trials, where it may contribute to understanding the sources of variability in clinical toxicity and treatment discontinuation.