TY - JOUR
T1 - A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, Emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy
AU - Davis, Ian D.
AU - Kiers, Lynette
AU - MacGregor, Lachlan
AU - Quinn, Michael
AU - Arezzo, Joseph
AU - Green, Michael
AU - Rosenthal, Mark
AU - Chia, Michael
AU - Michael, Michael
AU - Bartley, Peter
AU - Harrison, Leonie
AU - Daly, Michael
PY - 2005/3/1
Y1 - 2005/3/1
N2 - Purpose: To determine whether recombinant human leukemia inhibitory factor (rhuLIF, AM424, emfilermin) can prevent or ameliorate the development of chemotherapy-induced peripheral neuropathy (CIPN) after treatment with carboplatin (AUC 6) and paclitaxel (175 mg/m2 over 3 hours). Experimental Design: Randomized double-blind placebo-controlled phase II clinical trial. Eligible patients had solid tumors for which treatment with carboplatin/paclitaxel was appropriate. The primary end point was a standardized composite peripheral nerve electrophysiology (CPNE) score, based on nerve velocities and amplitudes, measured at baseline and after four cycles of chemotherapy. Secondary efficacy end points included CPNE score at last cycle and at exit evaluation, vibration perception threshold, H-reflex latency, symptom scores, and quantitative assessment of neurologic signs. Study drug was given s.c. daily for 7 days starting the day before chemotherapy. Patients were randomized to receive low-dose rhuLIF (2 μg/kg), high-dose rhuLIF (4 μg/kg), or placebo. Results: Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 μg/kg), 39 received high dose rhuLIF (4 μg/kg) and 42 received placebo. rhuLIF was well tolerated with 95% compliance and no adverse effects on quality of life. No differences between groups in CPNE or any of the individual neurologic testing variables were observed between baseline and cycle 4 or by the secondary efficacy variables. Conclusions: rhuLIF is not effective in preventing CIPN caused by carboplatin and paclitaxel. CPNE is a reliable and valid tool that was sensitive to the onset and progression of CIPN.
AB - Purpose: To determine whether recombinant human leukemia inhibitory factor (rhuLIF, AM424, emfilermin) can prevent or ameliorate the development of chemotherapy-induced peripheral neuropathy (CIPN) after treatment with carboplatin (AUC 6) and paclitaxel (175 mg/m2 over 3 hours). Experimental Design: Randomized double-blind placebo-controlled phase II clinical trial. Eligible patients had solid tumors for which treatment with carboplatin/paclitaxel was appropriate. The primary end point was a standardized composite peripheral nerve electrophysiology (CPNE) score, based on nerve velocities and amplitudes, measured at baseline and after four cycles of chemotherapy. Secondary efficacy end points included CPNE score at last cycle and at exit evaluation, vibration perception threshold, H-reflex latency, symptom scores, and quantitative assessment of neurologic signs. Study drug was given s.c. daily for 7 days starting the day before chemotherapy. Patients were randomized to receive low-dose rhuLIF (2 μg/kg), high-dose rhuLIF (4 μg/kg), or placebo. Results: Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 μg/kg), 39 received high dose rhuLIF (4 μg/kg) and 42 received placebo. rhuLIF was well tolerated with 95% compliance and no adverse effects on quality of life. No differences between groups in CPNE or any of the individual neurologic testing variables were observed between baseline and cycle 4 or by the secondary efficacy variables. Conclusions: rhuLIF is not effective in preventing CIPN caused by carboplatin and paclitaxel. CPNE is a reliable and valid tool that was sensitive to the onset and progression of CIPN.
UR - http://www.scopus.com/inward/record.url?scp=20144387524&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-04-1655
DO - 10.1158/1078-0432.CCR-04-1655
M3 - Article
C2 - 15756015
AN - SCOPUS:20144387524
SN - 1078-0432
VL - 11
SP - 1890
EP - 1898
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 5
ER -