North Central Cancer Treatment Group/Alliance trial N08CA - The use of glutathione for prevention of paclitaxel/carboplatin-induced peripheral neuropathy

A phase 3 randomized, double-blind, placebo-controlled study

Alexis D. Leal, Rui Qin, Pamela J. Atherton, Paul Haluska, Robert J. Behrens, Charles H. Tiber, Patanit Watanaboonyakhet, Matthias Weiss, Paul T. Adams, Travis J. Dockter, Charles Lawrence Loprinzi

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of taxane and platinum-based chemotherapy. Several studies have supported the potential benefit of glutathione for the prevention of platinum-induced CIPN. The current trial was designed to determine whether glutathione would prevent CIPN as a result of carboplatin/paclitaxel therapy. METHODS In total, 185 patients who received treatment with paclitaxel and carboplatin were accrued between December 4, 2009 and December 19, 2011. Patients were randomized to receive either placebo (n = 91) or 1.5 g/m 2 glutathione (n = 94) over 15 minutes immediately before chemotherapy. CIPN was assessed using the European Organization for Research and Treatment of Cancer Quality-of-Life (EORTC-QLQ) 20-item, CIPN-specific (CIPN20) sensory subscale and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. RESULTS There were no statistically significant differences between the 2 study arms with regard to: 1) peripheral neurotoxicity, as assessed using both the EORTC-QLQ-CIPN20 (P = .21) and the CTCAE scales (P = .449 for grade ≥2 neurotoxicity; P = .039 for time to development of grade ≥2 neuropathy, in favor of the placebo); 2) the degree of paclitaxel acute pain syndrome (P = .30 for patients who received paclitaxel every 3-4 weeks and P = .002, in favor of the placebo, for patients who received weekly paclitaxel); 3) the time to disease progression (P = .63); or 4) apparent toxicities. Subgroup analyses did not reveal any evidence of benefit in any particular subgroup. CONCLUSIONS The results from this study do not support the use of glutathione for the prevention of paclitaxel/carboplatin-induced CIPN.

Original languageEnglish (US)
Pages (from-to)1890-1897
Number of pages8
JournalCancer
Volume120
Issue number12
DOIs
StatePublished - Jun 15 2014

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Carboplatin
Peripheral Nervous System Diseases
Paclitaxel
Glutathione
Placebos
Drug Therapy
Neoplasms
Therapeutics
Platinum
Terminology
National Cancer Institute (U.S.)
Acute Pain
Disease Progression
Quality of Life
Organizations
Research

Keywords

  • carboplatin
  • chemotherapy-induced peripheral neuropathy
  • glutathione
  • paclitaxel
  • prevention

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

North Central Cancer Treatment Group/Alliance trial N08CA - The use of glutathione for prevention of paclitaxel/carboplatin-induced peripheral neuropathy : A phase 3 randomized, double-blind, placebo-controlled study. / Leal, Alexis D.; Qin, Rui; Atherton, Pamela J.; Haluska, Paul; Behrens, Robert J.; Tiber, Charles H.; Watanaboonyakhet, Patanit; Weiss, Matthias; Adams, Paul T.; Dockter, Travis J.; Loprinzi, Charles Lawrence.

In: Cancer, Vol. 120, No. 12, 15.06.2014, p. 1890-1897.

Research output: Contribution to journalArticle

Leal, Alexis D. ; Qin, Rui ; Atherton, Pamela J. ; Haluska, Paul ; Behrens, Robert J. ; Tiber, Charles H. ; Watanaboonyakhet, Patanit ; Weiss, Matthias ; Adams, Paul T. ; Dockter, Travis J. ; Loprinzi, Charles Lawrence. / North Central Cancer Treatment Group/Alliance trial N08CA - The use of glutathione for prevention of paclitaxel/carboplatin-induced peripheral neuropathy : A phase 3 randomized, double-blind, placebo-controlled study. In: Cancer. 2014 ; Vol. 120, No. 12. pp. 1890-1897.
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abstract = "BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of taxane and platinum-based chemotherapy. Several studies have supported the potential benefit of glutathione for the prevention of platinum-induced CIPN. The current trial was designed to determine whether glutathione would prevent CIPN as a result of carboplatin/paclitaxel therapy. METHODS In total, 185 patients who received treatment with paclitaxel and carboplatin were accrued between December 4, 2009 and December 19, 2011. Patients were randomized to receive either placebo (n = 91) or 1.5 g/m 2 glutathione (n = 94) over 15 minutes immediately before chemotherapy. CIPN was assessed using the European Organization for Research and Treatment of Cancer Quality-of-Life (EORTC-QLQ) 20-item, CIPN-specific (CIPN20) sensory subscale and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. RESULTS There were no statistically significant differences between the 2 study arms with regard to: 1) peripheral neurotoxicity, as assessed using both the EORTC-QLQ-CIPN20 (P = .21) and the CTCAE scales (P = .449 for grade ≥2 neurotoxicity; P = .039 for time to development of grade ≥2 neuropathy, in favor of the placebo); 2) the degree of paclitaxel acute pain syndrome (P = .30 for patients who received paclitaxel every 3-4 weeks and P = .002, in favor of the placebo, for patients who received weekly paclitaxel); 3) the time to disease progression (P = .63); or 4) apparent toxicities. Subgroup analyses did not reveal any evidence of benefit in any particular subgroup. CONCLUSIONS The results from this study do not support the use of glutathione for the prevention of paclitaxel/carboplatin-induced CIPN.",
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author = "Leal, {Alexis D.} and Rui Qin and Atherton, {Pamela J.} and Paul Haluska and Behrens, {Robert J.} and Tiber, {Charles H.} and Patanit Watanaboonyakhet and Matthias Weiss and Adams, {Paul T.} and Dockter, {Travis J.} and Loprinzi, {Charles Lawrence}",
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T1 - North Central Cancer Treatment Group/Alliance trial N08CA - The use of glutathione for prevention of paclitaxel/carboplatin-induced peripheral neuropathy

T2 - A phase 3 randomized, double-blind, placebo-controlled study

AU - Leal, Alexis D.

AU - Qin, Rui

AU - Atherton, Pamela J.

AU - Haluska, Paul

AU - Behrens, Robert J.

AU - Tiber, Charles H.

AU - Watanaboonyakhet, Patanit

AU - Weiss, Matthias

AU - Adams, Paul T.

AU - Dockter, Travis J.

AU - Loprinzi, Charles Lawrence

PY - 2014/6/15

Y1 - 2014/6/15

N2 - BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of taxane and platinum-based chemotherapy. Several studies have supported the potential benefit of glutathione for the prevention of platinum-induced CIPN. The current trial was designed to determine whether glutathione would prevent CIPN as a result of carboplatin/paclitaxel therapy. METHODS In total, 185 patients who received treatment with paclitaxel and carboplatin were accrued between December 4, 2009 and December 19, 2011. Patients were randomized to receive either placebo (n = 91) or 1.5 g/m 2 glutathione (n = 94) over 15 minutes immediately before chemotherapy. CIPN was assessed using the European Organization for Research and Treatment of Cancer Quality-of-Life (EORTC-QLQ) 20-item, CIPN-specific (CIPN20) sensory subscale and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. RESULTS There were no statistically significant differences between the 2 study arms with regard to: 1) peripheral neurotoxicity, as assessed using both the EORTC-QLQ-CIPN20 (P = .21) and the CTCAE scales (P = .449 for grade ≥2 neurotoxicity; P = .039 for time to development of grade ≥2 neuropathy, in favor of the placebo); 2) the degree of paclitaxel acute pain syndrome (P = .30 for patients who received paclitaxel every 3-4 weeks and P = .002, in favor of the placebo, for patients who received weekly paclitaxel); 3) the time to disease progression (P = .63); or 4) apparent toxicities. Subgroup analyses did not reveal any evidence of benefit in any particular subgroup. CONCLUSIONS The results from this study do not support the use of glutathione for the prevention of paclitaxel/carboplatin-induced CIPN.

AB - BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of taxane and platinum-based chemotherapy. Several studies have supported the potential benefit of glutathione for the prevention of platinum-induced CIPN. The current trial was designed to determine whether glutathione would prevent CIPN as a result of carboplatin/paclitaxel therapy. METHODS In total, 185 patients who received treatment with paclitaxel and carboplatin were accrued between December 4, 2009 and December 19, 2011. Patients were randomized to receive either placebo (n = 91) or 1.5 g/m 2 glutathione (n = 94) over 15 minutes immediately before chemotherapy. CIPN was assessed using the European Organization for Research and Treatment of Cancer Quality-of-Life (EORTC-QLQ) 20-item, CIPN-specific (CIPN20) sensory subscale and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. RESULTS There were no statistically significant differences between the 2 study arms with regard to: 1) peripheral neurotoxicity, as assessed using both the EORTC-QLQ-CIPN20 (P = .21) and the CTCAE scales (P = .449 for grade ≥2 neurotoxicity; P = .039 for time to development of grade ≥2 neuropathy, in favor of the placebo); 2) the degree of paclitaxel acute pain syndrome (P = .30 for patients who received paclitaxel every 3-4 weeks and P = .002, in favor of the placebo, for patients who received weekly paclitaxel); 3) the time to disease progression (P = .63); or 4) apparent toxicities. Subgroup analyses did not reveal any evidence of benefit in any particular subgroup. CONCLUSIONS The results from this study do not support the use of glutathione for the prevention of paclitaxel/carboplatin-induced CIPN.

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