Title: Phase I study of pulsatile 3-day administration of afatinib (BIBW 2992) in combination with docetaxel in advanced solid tumors
Authors: Awada, A H ×
Dumez, Herlinde
Hendlisz, A
Wolter, Pascal
Besse-Hammer, T
Uttenreuther-Fischer, M
Stopfer, P
Fleischer, F
Piccart, M
Schöffski, Patrick #
Issue Date: Jun-2013
Publisher: M. Nijhoff
Series Title: Investigational new drugs vol:31 issue:3 pages:734-741
Abstract: Background A phase I study to assess the maximum tolerated dose (MTD) of a short course of afatinib in combination with docetaxel for the treatment of solid tumors. Methods Patients with advanced solid malignancies received docetaxel 75 mg/m(2) intravenously on day 1 and oral afatinib once daily on days 2-4, in 3-week treatment cycles. The afatinib dose was escalated in successive cohorts of 3-6 patients until dose-limiting toxicity (DLT). The MTD cohort was expanded to 13 patients. Pharmacokinetic parameters were assessed. Results Forty patients were treated. Afatinib doses were escalated to 160 mg/day in combination with 75 mg/m(2) docetaxel. Three patients had drug-related DLTs during cycle 1. The MTD was defined as 90 mg/day afatinib (days 2-4) with docetaxel 75 mg/m(2). The most frequent drug-related adverse events (all grades) were alopecia, diarrhea, stomatitis (all 50 %) and rash (40 %, all grade ≤2). Three patients had confirmed responses, two patients had unconfirmed responses and nine patients had durable stable disease >6 cycles. No pharmacokinetic interaction was observed. Conclusion Afatinib 90 mg administered for 3 days after docetaxel 75 mg/m(2) is the MTD for this treatment schedule and the recommended phase II/phase III dose. This combination showed anti-tumor activity in phase I, with a manageable adverse-event profile.
ISSN: 0167-6997
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Oncology
× corresponding author
# (joint) last author

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