A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy.
OBJECTIVE
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/m(2) over 3 hours).


METHODS
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 microg/kg), high-dose rhuLIF (4 microg/kg), or placebo.


RESULTS
Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 microg/kg), 39 received high dose rhuLIF (4 microg/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.
Davis
Ian D
ID
Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia. Ian.Davis@ludwig.edu.au
Kiers
Lynette
L
MacGregor
Lachlan
L
Quinn
Michael
M
Arezzo
Joseph
J
Green
Michael
M
Rosenthal
Mark
M
Chia
Michael
M
Michael
Michael
M
Bartley
Peter
P
Harrison
Leonie
L
Daly
Michael
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D016207:Cytokines; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008049:Lipase; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D009431:Neural Conduction; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D010919:Placebos; D011446:Prospective Studies; D011506:Proteins / Q000008:administration & dosage / Q000627:therapeutic use*
D016207:Cytokines; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D010919:Placebos; D011506:Proteins; D016190:Carboplatin; D008049:Lipase; D017239:Paclitaxel