Human leukemia inhibitory factor (LIF) is an interleukin class cytokine that inhibits cell differentiation. Recombinant human LIF was evaluated for its effect on chemotherapy-induced peripheral neuropathy in patients with cancer.
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 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.
Stubblefield, M.D., Burstein, H.J., Burton, A.W., Custodio, C.M., Deng, G.E., Ho, M., . . . Von Roenn, J.H. (2009). NCCN task force report: Management of neuropathy in cancer. Journal of the National Comprehensive Cancer Network, 7(Suppl., 5), S1–S26.
This study outlines the common antineoplastic agents known to cause neuropathy and provides information on incidence, onset dosages, the signs and symptoms, and general course and patterns of resolution. Agents identified include platinum compounds, vinca alkaloids, taxanes, bortezomib, ixabepilone, thalidomide, and lenalidomide. In addition to outlining the mechanisms of neuropathy development in cancer, the study discusses neurophysiologic and objective testing, noting that findings on electromyographic (EMG) and nerve conduction studies (NCS) can lag behind clinical symptoms. The study also identifies commonly used physician-based grading systems, including the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) and Eastern Cooperative Oncology Group (ECOG) systems, and notes that these two grading systems lack inter-rater reliability. Patient-based instruments for assessment include the Functional Assessment of Cancer Treatment (FACT) and the Patient Neurotoxicity Questionnaire (PNQ). The authors note that the routine assessment of pain secondary to neuropathy, using instruments such as the Brief Pain Inventory (BPI), is useful.
Routine assessment should be conducted and continued throughout therapy. Key points in assessment that should be included are:
Proposed agents for prevention of CIPN identified include:
Agents used for pain management:
Current literature is inconclusive on the benefits of neurostimulation in treating CIPN. The authors note that evidence is scarce on efficacy of complimentary and alternative medicine (CAM) therapies and the need for appropriately powered and controlled studies in this area. However, acupuncture was identified as a promising adjunct option. The article also provides safety tips and issues for management of functional deficits in PIN, including situations in which to avoid or discontinue physical training, footwear selection, orthosis, and safety aspects of the household environment. Finally, the article addresses how autonomic neuropathy from chemotherapy occurs, but has not been well documented or studied.
The article provides a comprehensive review of current knowledge about CIPN and common approaches toward assessment, prevention, and management. The authors do not make specific recommendations for treatment, research to validate evaluation tools, and exploration of combinations and scheduling of pain medications. In addition, testing of the safety and effectiveness of therapeutic interventions and dietary supplements are needed.