Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a phase I open-label dose escalation study.
OBJECTIVE
Evaluate the safety, tolerability and preliminary efficacy of intracoronary (IC) basic fibroblast growth factor (bFGF, FGF-2).


BACKGROUND
FGF-2 is a heparin-binding growth factor capable of inducing functionally significant angiogenesis in animal models of myocardial ischemia.


METHODS
Phase I, open-label dose-escalation study of FGF-2 administered as a single 20-min infusion in patients with ischemic heart disease not amenable to treatment with CABG or PTCA.


RESULTS
Fifty-two patients enrolled in this study received IC FGF-2 (0.33 to 48 microg/kg). Hypotension was dose-dependent and dose-limiting, with 36 microg/kg being the maximally tolerated dose. Four patients died and four patients had non-Q-wave myocardial infarctions. Laboratory parameters and retinal examinations showed mild and mainly transient changes during the 6-month follow-up. There was an improvement in quality of life as assessed by Seattle Angina Questionnaire and improvement in exercise tolerance as assessed by treadmill exercise testing (510+/-24 s at baseline, 561+/-26 s at day 29 [p = 0.023], 609+/-26 s at day 57 (p < 0.001), and 633+/-24 s at day 180 (p < 0.001), overall p < 0.001). Magnetic resonance (MR) imaging showed increased regional wall thickening (baseline: 34+/-1.7%, day 29: 38.7+/-1.9% [p = 0.006], day 57: 41.4+/-1.9% [p < 0.001], and day 180: 42.0+/-2.3% [p < 0.001], overall p = 0.001) and a reduction in the extent of the ischemic area at all time points compared with baseline.


CONCLUSIONS
Intracoronary administration of rFGF-2 appears safe and is well tolerated over a 100-fold dose range (0.33 to 0.36 microk/kg). Preliminary evidence of efficacy is tempered by the open-label uncontrolled design of the study.
Laham
R J
RJ
Angiogenesis Research Center and Interventional Cardiology Section, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Chronos
N A
NA
Pike
M
M
Leimbach
M E
ME
Udelson
J E
JE
Pearlman
J D
JD
Pettigrew
R I
RI
Whitehouse
M J
MJ
Yoshizawa
C
C
Simons
M
M
D000368:Aged; D005080:Exercise Test; D005240:Feasibility Studies; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy*
D016222:Fibroblast Growth Factor 2