Article Figures & Data
Figures
- Fig. 1.
Treatment schema for intermittent and continuous dosing schedules of TKI258. Shaded boxes, “on drug” days; unshaded boxes, “off drug” days. For the intermittent schedule, DLT was defined as occurring in the first 28 d (cycle 1). For the continuous schedule, DLT was defined as occurring in the 7-d/7-d off intermittent lead-in period and the first 14 d of continuous dosing.
- Fig. 2.
Plasma pharmacokinetics of TKI258 in patients with solid tumors. Plasma mean (±SD) Cmax (A) and area under the curve (AUC; B) are shown for each dose cohort and show dose proportionality.
- Fig. 3.
Changes in ERK phosphorylation in PBMCs with TKI258 in a patient treated at 75 mg (intermittent schedule). This patient had inhibition of ERK phosphorylation detectable at day 1, 4 h, which was maintained on day 7, and after redosing on day 15 at 4 and 24 h. pERK, phosphorylated ERK. Positive control samples are blood cells from a normal donor processed identically to clinical samples as indication of basal levels.
- Fig. 4.
Evidence of tumor shrinkage on computed tomography scan in a patient with metastatic melanoma. Computed tomography shows reduction in size of liver metastasis with TKI258 at 175 mg continuous dosing. This patient achieved a partial response after 9 mo of TKI258 and continues on treatment at the present time.
Tables
- Table 1.
Baseline characteristics
Characteristics n Patients 35 Male 20 Female 15 Median age, y (range) 56 (30-71) ECOG PS 0 16 1 19 Prior chemotherapy 0-3 23 4-6 9 >6 3 Tumor types Renal 6 Prostate 5 CRC 5 Melanoma 3 GIST 2 Sarcoma 2 Gastric 2 Esophageal 2 Other* 8 Abbreviations: PS, performance status; CRC, colorectal; GIST, gastrointestinal stromal tumor.
↵* Other: breast, parotid, carcinoma unknown primary, dermatofibrosarcoma protuberans, sinonasal neuroendocrine tumor, ovarian, and nasopharyngeal.
- Table 2.
Clinical adverse events
Adverse event Grade 25 50 75 100 100* 125* 175* Fatigue 2 3 1 1 1 1 0 1 3-4 0 0 0 0 0 0 3 Anemia 2 1 1 3 0 0 0 3 3-4 2 0 0 0 0 1 0 Nausea 2 0 1 1 1 0 0 3 3-4 1 1 1 0 0 1 0 Vomiting 2 1 0 1 2 0 0 1 3-4 0 1 1 0 0 1 0 Diarrhea 2 0 0 1 0 0 0 0 3-4 1 0 0 0 0 0 0 Headache 2 0 2 0 1 0 0 1 3-4 0 1 0 0 0 0 0 Anorexia 2 2 0 0 1 0 1 1 3-4 0 0 0 0 0 0 1 Reduced LVEF 2 0 0 1 1 0 0 0 3-4 0 0 0 0 0 0 0 Hypertension 2 0 0 0 0 1 0 0 3-4 0 0 0 0 1 0 0 Pulmonary embolism 2 0 0 0 0 0 0 0 3-4 0 0 0 0 0 2 0 Troponin I increase 2 0 0 0 0 0 0 0 3-4 0 0 0 0 0 1 0 ALP elevation 2 0 0 0 0 0 1 2 3-4 0 0 0 0 0 1 2 Abbreviation: ALP, alkaline phosphatase.
↵* Continuous schedule.
Volume 14, Issue 7
