A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, Emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy

Ian D. Davis, Lynette Kiers, Lachlan MacGregor, Michael Quinn, Joseph C. Arezzo, Michael Green, Mark Rosenthal, Michael Chia, Michael Michael, Peter Bartley, Leonie Harrison, Michael Daly

Research output: Contribution to journalArticle

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Abstract

Purpose: 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/m2 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 μg/kg), high-dose rhuLIF (4 μg/kg), or placebo. Results: Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 μg/kg), 39 received high dose rhuLIF (4 μg/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.

Original languageEnglish (US)
Pages (from-to)1890-1898
Number of pages9
JournalClinical Cancer Research
Volume11
Issue number5
DOIs
StatePublished - Mar 1 2005

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Leukemia Inhibitory Factor
Peripheral Nervous System Diseases
Electrophysiology
Peripheral Nerves
Placebos
Carboplatin
Drug Therapy
Paclitaxel
H-Reflex
Phase II Clinical Trials
Controlled Clinical Trials
Neurology
Neurologic Manifestations
Vibration
Nervous System
Compliance
Area Under Curve
Research Design
Quality of Life
human LIF protein

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, Emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy. / Davis, Ian D.; Kiers, Lynette; MacGregor, Lachlan; Quinn, Michael; Arezzo, Joseph C.; Green, Michael; Rosenthal, Mark; Chia, Michael; Michael, Michael; Bartley, Peter; Harrison, Leonie; Daly, Michael.

In: Clinical Cancer Research, Vol. 11, No. 5, 01.03.2005, p. 1890-1898.

Research output: Contribution to journalArticle

Davis, Ian D. ; Kiers, Lynette ; MacGregor, Lachlan ; Quinn, Michael ; Arezzo, Joseph C. ; Green, Michael ; Rosenthal, Mark ; Chia, Michael ; Michael, Michael ; Bartley, Peter ; Harrison, Leonie ; Daly, Michael. / A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, Emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 5. pp. 1890-1898.
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abstract = "Purpose: 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/m2 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 μg/kg), high-dose rhuLIF (4 μg/kg), or placebo. Results: Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 μg/kg), 39 received high dose rhuLIF (4 μg/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.",
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T1 - A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, Emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy

AU - Davis, Ian D.

AU - Kiers, Lynette

AU - MacGregor, Lachlan

AU - Quinn, Michael

AU - Arezzo, Joseph C.

AU - Green, Michael

AU - Rosenthal, Mark

AU - Chia, Michael

AU - Michael, Michael

AU - Bartley, Peter

AU - Harrison, Leonie

AU - Daly, Michael

PY - 2005/3/1

Y1 - 2005/3/1

N2 - Purpose: 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/m2 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 μg/kg), high-dose rhuLIF (4 μg/kg), or placebo. Results: Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 μg/kg), 39 received high dose rhuLIF (4 μg/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.

AB - Purpose: 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/m2 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 μg/kg), high-dose rhuLIF (4 μg/kg), or placebo. Results: Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 μg/kg), 39 received high dose rhuLIF (4 μg/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.

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