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

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 gl...

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Published in:	Cancer Vol. 120; no. 12; pp. 1890 - 1897
Main Authors:	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 L.
Format:	Journal Article
Language:	English
Published:	Hoboken, NJ Wiley-Blackwell 15-06-2014
Subjects:	Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences carboplatin Carboplatin - administration & dosage Carboplatin - adverse effects chemotherapy‐induced peripheral neuropathy Double-Blind Method Female glutathione Glutathione - therapeutic use Humans Male Medical sciences Middle Aged Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neoplasms - drug therapy paclitaxel Paclitaxel - administration & dosage Paclitaxel - adverse effects Peripheral Nervous System Diseases - chemically induced Peripheral Nervous System Diseases - prevention & control Placebos prevention Tumors Antineoplastic agent Nervous system diseases Use chemotherapy-induced peripheral neuropathy Malignant tumor Prevention Chemotherapy Randomization Treatment Cancerology Taxane derivatives Paclitaxel Placebo Carboplatin Double blind study Clinical trial Peripheral nerve disease Antimitotic Platinum II Complexes Cancer Glutathione paclitaxel carboplatin glutathione prevention
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Summary:	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/m2 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. Cancer 2014;120:1890–1897. © 2014 American Cancer Society. Glutathione is not effective in preventing paclitaxel/carboplatin‐induced peripheral neuropathy. In addition, it does not appear to interfere with the antitumor activity of paclitaxel/carboplatin.
Bibliography:	Additional participating institutions include: Siouxland Hematology‐Oncology Associates, Sioux City, Iowa (Donald Wender, MD); Medical College of Georgia, Augusta, Ga (Anand P. Jillella, MD); Colorado Cancer Research Program, Denver, Colo (Eduardo R. Pajon, Jr, MD); Mayo Clinic Arizona, Scottsdale, Ariz (Michele Y. Halyard, MD); Medcenter One Health Systems, Bismarck, ND (Keren Sturtz, MD); Carle Cancer Center Community Clinical Oncology Program (CCOP), Urbana, Ill (Kendrith M. Rowland, Jr, MD); Essentia Duluth CCOP, Duluth, Minn (Daniel A. Nikcevich, MD); Metro‐Minnesota CCOP, St. Louis Park, Minn (Daniel M. Anderson, MD); Missouri Valley Cancer Consortium, Omaha, Neb (Gamini S. Soori, MD); St. Vincent Regional Cancer Center CCOP, Green Bay, Wis (Anthony J. Jaslowski, MD); Hematology & Oncology of Dayton, Inc., Dayton, Ohio (Howard M. Gross, MD); Wichita CCOP, Wichita, Kan (Shaker R. Dakhil, MD); Edward Comprehensive Cancer Center, Huntington, WVa (Maria Rosalia B. Tri Tirona, MD); Ochsner CCOP, New Orleans, La (Jyotsna Fuloria, MD); Sioux Community Cancer Consortium, Sioux Falls, SD (Miroslaw Mazurczak, MD); Virginia Mason CCOP, Seattle, Wash (Craig R. Nichols, MD); Hawaii Minority‐Based CCOP, Honolulu, Hawaii (Jeffrey L. Berenberg, MD); Cedar Rapids Oncology Project CCOP, Cedar Rapids, Iowa (Deborah Weil Wilbur, MD); and Geisinger Clinic and Medical Center CCOP, Danville, Pa (Maged Khalil, MD).
ISSN:	0008-543X 1097-0142
DOI:	10.1002/cncr.28654