Article Figures & Data
Figures
- Fig. 1.
A, maximum change from baseline in tumor size per daily dose group. All patients evaluable for iAUC change and MRI imaging; black columns, patients with colorectal cancer; light gray columns, patients with kidney/ureter cancer. B, mean change and SEM in iAUC60 from baseline at day 2, day 30, day 56, and day 84 by daily dose group.
- Fig. 2.
Arithmetic mean plasma concentration-time profiles of BIBF 1120 after single and multiple administrations of 150 and 250 mg BIBF 1120 twice daily over 29 (+1/−2) days (±SD).
Tables
- Table 1.
Patient characteristics
Characteristics BIBF 1120 Once daily Twice daily No. of patients 25 36 Gender Male (n) 15 31 Female (n) 10 5 Age 59 (41-74) 63 (34-83) Median (range) ECOG performance status at baseline 0 7 9 1 17 26 2 1 1 Prior therapy Surgery 23 33 Chemotherapy 24 29 Radiotherapy 9 15 Immunotherapy* 5 8 Hormonal therapy 1 4 Tumor type Colorectal 14 16 Kidney, ureter 1 9 Pleura 3 2 Prostate 0 3 Breast 2 0 Sarcoma, soft tissue 1 1 Head and neck 0 2 Lung 0 2 Pancreas 1 0 Liver, biliary tree 2 0 Cervix, vagina and vulva 1 0 Thyroid 0 1 Abbreviation: ECOG, Eastern Cooperative Oncology Group.
↵*Immunotherapy comprised, e.g., IFN, interleukin, levamisole.
- Table 2.
Number of patients with BIBF 1120–related adverse events occurring in >5% of patients
Adverse event* Maximum grade (CTC) BIBF 1120 Once daily Twice daily First, n (%) All courses, n (%) First, n (%) All courses, n (%) All patients 25 25 36 36 Patients with adverse event 21 (84) 24 (96) 30 (83.3) 33 (91.7) Nausea 1 13 (52) 13 (52) 17 (47.2) 19 (52.8) 2 4 (16) 5 (20) 2 (5.6) 3 (8.3) 3 0 0 2 (5.6) 2 (5.6) Vomiting 1 7 (28) 9 (36) 10 (27.8) 15 (41.7) 2 3 (12) 3 (12) 0 0 3 0 0 1 (2.8) 1 (2.8) Diarrhea 1 6 (24) 6 (24) 9 (25) 13 (36.1) 2 5 (20) 6 (24) 1 (2.8) 1 (2.8) 3 0 0 0 1 (2.8) Dyspepsia 1 2 (8) 2 (8) 0 2 (5.6) Anorexia 1 0 2 (8) 0 0 Abdominal pain 2 2 (8) 2 (8) 0 0 Fatigue 1 2 (8) 3 (12) 4 (11.1) 4 (11.1) 2 0 0 4 (11.1) 5 (13.9) Dizziness 1 0 0 4 (11.1) 5 (13.9) Pruritus 1 0 4 (16) 0 0 Urticaria 1 0 0 0 2 (5.6) Hepatic enzyme elevation†‡ 2 1 (4) 1 (4) 0 0 3 3 (12) 3 (12) 0 0 4 1 (4) 1 (4) 1 (2.8) 1 (2.8) ALT increase† 2 0 0 1 (2.8) 1 (2.8) 3 0 0 1 (2.8) 2 (5.6) AST increase† 2 0 0 1 (2.8) 0 3 1 (4) 2 (8) 1 (2.8) 1 (2.8) γ-GT increase† 2 0 0 1 (2.8) 1 (2.8) 3 1 (4) 1 (4) 1 (2.8) 2 (5.6) CD4 lymphocytes decreased† 3 1 (4) 4 (16) 2 (5.6) 2 (5.6) Hypertension† 1 0 0 0 2 (5.6) 2 1 (4) 1 (4) 0 0 3 0 1 (4) 0 0 Headache 1 0 2 (8) 2 (5.6) 2 (5.6) Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; γ-GT, γ glutamyl transpeptidase.
↵*Preferred terms.
↵†Number of patients with adverse events occurring in >1% of patients. Presented is the highest ever reached CTC grade. The same patient may have experienced more than one event.
↵‡Hepatic enzyme elevation describes the following cases that were presented under the respective highest CTC grade. Twice daily cohort: one patient had AST of grade 4 and ALT + γGT grade 3. Once daily cohort: one patient had ALT+AST of grade 4 +γGT grade 3, one patient had ALT+γGT of grade 3, one patient had AST+γGT of grade 3, one patient had ALT+AST of grade 3 and one patient had ALT of grade 2.
- Table 3.
Number of patients with DLT within the first course of BIBF 1120 treatment
Total daily dose (mg) Once daily Twice daily All patients Patients with DLT All patients Patients with DLT 50 2 0 — — 100 1 0 — — 150 — — 6 0 150 + 200 — — 6 0 200 8 1 (12.5) AST+γGT increased 6 1 (16.7) CD4 lymphocytes decreased 250 6 1 (16.7) CD4 lymphocytes decreased 13 1 (7.7) nausea 300 5 2 (40) AST+γGT (1), ALT+AST (1) 5 4 (80) nausea+vomiting (1), ALT+AST increased (1), ALT+AST+γGT (1), CD4 lymphocytes decreased + γGT, increased (1) 450 3 2 (66.7) ALT+AST+γGT (1), ALT+γGT (1) — — NOTE: DLT was defined as any CTC grade 3 or 4 hematologic or nonhematologic toxicity.
- Table 4.
Pharmacokinetic parameters of BIBF 1120 at steady state (day 29) in the first treatment course
BIBF 1120 dose (mg) No. of patients Cmax,ss ng/mL (gCV%) AUCτ,ss ng·h/mL (gCV%) tmax,ss* h (range) t1/2,ss h (gCV%) Once daily 50 1 8.22 32.1 3.07 14.7 100 1 40.8 207 2.00 11.8 200 8 35.4 (31.0) 223 (40.3) 1.98 (0.50-4.03) 15.3 (46.8) 250 6 58.6 (38.8) 479 (49.1) 2.53 (1.03-6.00) 13.7 (11.9)† 300 3 50.5 (137) 482 (128) 3.00 (2.92-4.03) 14.1 (35.7) Twice daily 150 6 34.8 (49.0) 171 (56.2) 1.03 (0.517-3.17) 16.3 (10.4)‡ 150+200 6 48.0 (70.0) 260 (57.3) 2.13 (1.00-4.03) 15.6 (36.6) 200 6 44.9 (80.5) 303 (81.2) 2.72 (1.00-7.92) 19.0 (60.0) 250 11 44.2 (54.3) 226 (55.6) 2.08 (0.517-4.08) 16.7 (35.2)§ 300 3 68.6 (20.6) 366 (9.57) 2.00 (1.05-2.22) 12.9 (37.1) NOTE: Presented is geometric mean. AUCτ,ss for once daily τ = 24 h; for twice daily τ = 12 h. No steady-state pharmacokinetic data could be collected for the 450 mg cohort due to drop out of the patients.
Abbreviation: gCV, geometric mean of the coefficient of variation.
Volume 16, Issue 1
