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.

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 total sample consisted of 117 patients diagnosed with solid tumor requiring chemotherapy of at least four cycles of carboplatin/paclitaxel.
• Exclusion criteria included having a clinically significant medical condition, having more than one prior course of chemotherapy for metastatic disease, having any prior neurotoxic chemotherapy requiring dose modification due to neuropathy, having brain metastasis, a history of alcoholism, or having preexisting neuropathy

The study had a phase II, double-blind, placebo-controlled clinical trial design.

• Neurologic assessments were performed prior to study drug administration following the fourth cycle of chemotherapy and last cycle of chemotherapy and at 3 months post chemotherapy.
• CPNE assessment consisted of peripheral nerve electrophysiology testing (antidromic maximal conduction velocity), amplitudes of three sensory nerves (sural, median and ulnar) and one motor nerve (peroneal) and vibration threshold of the non-dominant great toe.
• Neurologic signs were measured using the Einstein Neurologic Examination, assessed as 0 (absence of deficit) to 3 (severe, bilateral deficit involving proximal sites). A total score is obtained ranging from 0–15.
• Change in symptoms was measured using a subset of questions from the CIPNS-32. The severity of each symptom (0–4) and the extent it interfered with normal function (0–5) were rated on a scale, with a total possible score ranging from 0–100.

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.