Table 1.

Summary of NCI-supported CIPN prevention and treatment trials

Study	Year of approval	Design	Agent	Population	Number of patients	Results
Prevention trials
MDA-CCC-03-27 [9]	2004	Phase III, randomized, double-blind, placebo-controlled	Alpha lipoic acid	Patients receiving cisplatin or oxaliplatin	243	No difference in FACT-NTX, BPI score, pain or functional testing at 24 weeks
NCCTG N04C7 [10]	2004	Phase III, randomized, double-blind, placebo-controlled	Intravenous CaMg	Patients receiving oxaliplatin	102	Study stopped early due to an errant concern regarding CaMg; preliminary data from this study looked promising
NCCTG-N05C3 [11]	2006	Phase III, randomized, double-blind, placebo-controlled	Vitamin E	Patients receiving oxaliplatin, cisplatin, carboplatin or taxanes	207	No difference in grade 2+ neuropathy; no difference in time to neuropathy; no difference in patient reported CIPN scores 6 months following treatment
SWOG-S0715 [12]	2009	Phase III, randomized, double-blind, placebo-controlled	Acetyl-L-carnitine	Breast cancer patients receiving taxanes	409	No difference in CIPN at 12 weeks with the 11-item neurotoxicity component of the FACT-Taxane scale; increased CIPN at 24 weeks in the intervention arm
NCCTG-N08CA [13]	2009	Phase III, randomized, double-blind, placebo-controlled	Glutathione	Patients receiving taxanes	185	No difference measured by EORTC-CIPN20 sensory subscale and the CTCAE, version 4.0 following 6 cycles; increased time to CIPN favoring placebo
NCCTG-N08CB [14]	2009	Phase III, randomized, double-blind, placebo-controlled	Intravenous CaMg	Patients receiving oxaliplatin	353	Convincing lack of benefit in terms of CIPN prevention
GOG-0257	2012	Phase III, randomized, double-blind, placebo-controlled	Acetyl-L-carnitine	N/A	N/A	Withdrawn following results of SWOG 0715
Treatment trials
NCCTG-93-95-92 [15]	1995	Phase III, randomized, double-blind, placebo-controlled, cross-over	Nortriptyline	Pre-existing neuropathy related to chemotherapy treatment	51	No significant difference in quality of life measures and impact of symptoms on daily activities
NCCTG-N00C3 [16]	2002	Phase III, randomized, double-blind, placebo-controlled, cross-over	Gabapentin	Pre-existing neuropathy related to chemotherapy treatment	115	No difference between groups in pain measured by several at 6 and 14 weeks
NCCTG- N01C3 [17]	2003	Phase III, randomized, double-blind, placebo-controlled	Lamotrigine	Pre-existing neuropathy related to chemotherapy treatment	131	No difference in pain measured by several neuropathy scores
MDA-CCC-02-23 and GOG-0192	2003	N/A	Amifostine	Patients 2–12 months post taxane therapy with neuropathy	N/A	Closed due to poor accrual
URCC-06-05 [18]	2007	Phase III, randomized, double-blind, placebo-controlled	Topical amitriptyline and ketamine	Pre-existing neuropathy related to prior chemotherapy treatment	462	No difference in pain, numbness, and tingling scores at 6 weeks
NCCTG-N06CA [19]	2008	Phase III, randomized, double-blind, placebo-controlled	Topical BAK	Pre-existing neuropathy related to prior chemotherapy treatment	208	Mean decrease in EORTC-CIPN20 sensory scale for the BAK arm compared to placebo arm; also, decrease in motor subscale
CALGB-170601 [20]	2008	Phase III, randomized, double-blind, placebo-controlled, cross-over	Duloxetine	Pre-existing neuropathy related to prior taxane of platinum chemotherapy treatment	231	Decrease in pain score in the duloxetine group compared to those receiving placebo at 6 weeks

FACT-NTX Functional Assessment of Cancer Therapy-Neurotoxicity, BPI Brief Pain Inventory, CaMg calcium and magnesium, EORTC-CIPN20 European Organization for Research and Treatment of Cancer-Chemotherapy-Induced Peripheral Neuropathy 20, CTCAE Common Terminology Criteria for Adverse Events, BAK baclofen, amitriptyline HCl, and ketamine