Davis, I.D., Kiers, L., MacGregor, L., Quinn, M., Arezzo, J., Green, M., . . . Daly, M. (2005). A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AMg424) to prevent chemotherapy-induced peripheral neuropathy. Clinical Cancer Research, 11, 1890–1898.doi: 10.1158/1078-0432.CCR-04-1655
Patients were randomized to one of three study arms: 36 in the recombinant human leukemia inhibitory factor (rhu LIF) 2 mcg/kg group, 39 in the rhu LIF 4 mcg/kg group, or 42 in a placebo group. The study drug or placebo was administered one day prior to chemotherapy by subcutaneous injection after premedication with acetaminophen 1 g orally. The patient was then observed for two hours. The second injection was administered the following day, two hours prior to chemotherapy. The study drug or placebo was continued by daily subcutaneous injections for a total of seven consecutive doses per treatment cycle (every 21 days for 4–6 cycles).
The study had a phase II, double-blind, placebo-controlled clinical trial design.
rhu LIF was fairly well tolerated, with five patients reporting adverse events that included lightheadedness, rigors or chills, myocardial ischemia, and hypotension. CPNE scores showed small but consistent decrement between baseline and cycle 4 of chemotherapy. Vibration threshold was also altered by chemotherapy. Intent-to-treat analysis showed no significant differences in CPNE scores between the three groups.
No evidence showed that rhu LIF prevented, delayed, or diminished CIPN.
While sample size was calculated to be adequate by a power analysis, the goal of 40 patients per group was not achieved, and the original calculation may not have been accurate to achieve statistical significance.
Since the measures were sensitive enough to detect CIPN, no further plans to develop rhu LIF as an agent to treat or prevent CIPN were proposed.