A Randomized, Double-Blinded, Placebo-Controlled Phase II Trial of Recombinant Human Leukemia Inhibitory Factor (rhuLIF, Emfilermin, AM424) to Prevent Chemotherapy-Induced Peripheral Neuropathy

Abstract

Purpose: To determine whether recombinant human leukemia inhibitory factor (rhuLIF, AM424, emfilermin) can prevent or ameliorate the development of chemotherapyinduced peripheral neuropathy (CIPN) after treatment with carboplatin (AUC 6) and paclitaxel (175 mg/m 2 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 Mg/kg), high-dose rhuLIF (4 Mg/kg), or placebo.Results: Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 Mg/kg), 39 received high dose rhuLIF (4 Mg/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.

Neuropathy Secondary to Chemotherapy: A Real Issue for Cancer Survivors

“…Leukaemia inhibitory factor, which is a cytokine involved in the differentiation of stem cells and the regeneration of neurons, was tested in a randomised, double-blind, placebo-controlled clinical trial in paclitaxel-treated patients. The results were discouraging without any evidence of neuroprotection (Davis et al, 2005). NGF has been postulated as an effective protectant against cisplatin CIPN.…”

Assessment and Treatment of Chemotherapy-induced Peripheral Neuropathy- a Physical Therapy Perspective

“…Acety-L-Carnitine [65], Alpha-lipoic acid [66], Amifostine [67], cholest-4-en-3-one, oxime (TRO19622) [68], Cannabinoid type-1 receptor [69], Gabapentin [70], Glutamine [71], Lamotrigine [72], recombinant human leukemia inhibitory factor (rhuLIF, AM424, emfilermin) [73], Neurosteroids [74], Palmitoylethanolamide [75] and Retinoic acid [76] were studied individually for their efficacy in randomized clinical trials.…”

Obwodowa neuropatia wywołana chemioterapią. Część II. Zapobieganie

“…Badania modelowe wykazały działanie zabezpieczające interleukiny 6 w przypadku CIPN po paklitakselu, cisplatynie i winkrystynie [32]. Kolejne doświadczenia w warunkach klinicznych u pacjentów nie potwierdziły założonego działania profilaktycznego, ponieważ nie stwierdzono istotnych różnic między grupą pacjentów leczonych i otrzymujących placebo [33][34][35].…”