A phase I, open-label dose-escalation study of continuous treatment with BIBF 1120 in combination with paclitaxel and carboplatin as first-line treatment in patients with advanced non-small-cell lung cancer

作者：Doebele R C^*; Conkling P; Traynor A M; Otterson G A; Zhao Y; Wind S; Stopfer P; Kaiser R; Camidge D R

来源：Annals of Oncology, 2012, 23(8): 2094-2102.

DOI：10.1093/annonc/mdr596

• angiogenesis
• BIBF 1120
• chemotherapy
• NSCLC
• pharmacokinetics
• phase I

BIBF 1120 is an oral potent inhibitor of vascular endothelial growth factor receptor, fibroblast growth factor receptor and platelet-derived growth factor receptor, the three key receptor families involved in angiogenesis. This phase I, open-label dose-escalation study investigated BIBF 1120 combined with paclitaxel (Taxol) and carboplatin in first-line patients with advanced (IIIB/IV) non-small-cell lung cancer.
Patients received BIBF 1120 (starting dose 50 mg b.i.d.) on days 2-21 and paclitaxel (200 mg/m(2)) and carboplatin [area under curve (AUC) = 6 mg/ml/min] on day 1 of each 21-day cycle. Primary end points were safety and BIBF 1120 maximum tolerated dose (MTD) in this combination. Pharmacokinetics (PK) profiles were evaluated.
Twenty-six patients were treated (BIBF 1120 50-250 mg b.i.d.). BIBF 1120 MTD was 200 mg b.i.d. in combination with paclitaxel and carboplatin. Six dose-limiting toxicity events occurred during treatment cycle 1 (liver enzyme elevations, thrombocytopenia, abdominal pain, and rash). Best responses included 7 confirmed partial responses (26.9 % ); 10 patients had stable disease. BIBF 1120 200 mg b.i.d. had no clinically relevant influence on the PK of paclitaxel 200 mg/m(2) and carboplatin AUC 6 mg/ml/min and vice versa.
BIBF 1120 MTD was 200 mg b.i.d when given with paclitaxel and carboplatin; this combination demonstrated an acceptable safety profile. No relevant changes in PK parameters of the backbone chemotherapeutic agents or BIBF 1120 were observed.

• 出版日期2012-8