Clinical Course of Oxaliplatin-Induced Neuropathy: Results From the Randomized Phase III Trial N08CB (Alliance).
OBJECTIVE
Given that the clinical course of oxaliplatin-induced neuropathy is not well defined, the current study was performed to better understand clinical parameters associated with its presentation.


METHODS
Acute and chronic neuropathy was evaluated in patients receiving adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) on study N08CB (North Central Cancer Treatment Group, Alliance). Acute neuropathy was assessed by having patients complete daily questionnaires for 6 days with each cycle of FOLFOX. Before each dose of FOLFOX and as long as 18 months after chemotherapy cessation, chronic neurotoxicity was assessed with use of the 20-item, European Organisation for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy-induced peripheral neuropathy.


RESULTS
Three hundred eight (89%) of the 346 patients had at least one symptom of acute neuropathy with the first cycle of FOLFOX; these symptoms included sensitivity to touching cold items (71%), sensitivity to swallowing cold items (71%), throat discomfort (63%), or muscle cramps (42%). Acute symptoms peaked at day 3 and improved, although they did not always resolve completely between treatments. These symptoms were about twice as severe in cycles 2 through 12 as they were in cycle 1. For chronic neurotoxicity, tingling was the most severe symptom, followed by numbness and then pain. During chemotherapy, symptoms in the hands were more prominent than they were in the feet; by 18 months, symptoms were more severe in the feet than they were in the hands. Patients with more severe acute neuropathy during the first cycle of therapy experienced more chronic sensory neurotoxicity (P < .0001).


CONCLUSIONS
Acute oxaliplatin-induced neuropathy symptoms do not always completely resolve between treatment cycles and are only half as severe on the first cycle as compared with subsequent cycles. There is a correlation between the severities of acute and chronic neuropathies.
Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Kathryn J. Ruddy, Nathan P. Staff, Axel Grothey, and Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Ellen M.L. Smith, University of Michigan, Ann Arbor, MI; Nina D. Wagner-Johnston, Washington University School of Medicine, Saint Louis, MO; and Shaker Dakhil, Cancer Center of Kansas, Wichita, KS. pachman.deirdre@mayo.edu.
Deirdre R
DR
Pachman
Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Kathryn J. Ruddy, Nathan P. Staff, Axel Grothey, and Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Ellen M.L. Smith, University of Michigan, Ann Arbor, MI; Nina D. Wagner-Johnston, Washington University School of Medicine, Saint Louis, MO; and Shaker Dakhil, Cancer Center of Kansas, Wichita, KS.
Rui
R
Qin
Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Kathryn J. Ruddy, Nathan P. Staff, Axel Grothey, and Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Ellen M.L. Smith, University of Michigan, Ann Arbor, MI; Nina D. Wagner-Johnston, Washington University School of Medicine, Saint Louis, MO; and Shaker Dakhil, Cancer Center of Kansas, Wichita, KS.
Drew K
DK
Seisler
Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Kathryn J. Ruddy, Nathan P. Staff, Axel Grothey, and Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Ellen M.L. Smith, University of Michigan, Ann Arbor, MI; Nina D. Wagner-Johnston, Washington University School of Medicine, Saint Louis, MO; and Shaker Dakhil, Cancer Center of Kansas, Wichita, KS.
Ellen M L
EM
Smith
Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Kathryn J. Ruddy, Nathan P. Staff, Axel Grothey, and Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Ellen M.L. Smith, University of Michigan, Ann Arbor, MI; Nina D. Wagner-Johnston, Washington University School of Medicine, Saint Louis, MO; and Shaker Dakhil, Cancer Center of Kansas, Wichita, KS.
Andreas S
AS
Beutler
Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Kathryn J. Ruddy, Nathan P. Staff, Axel Grothey, and Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Ellen M.L. Smith, University of Michigan, Ann Arbor, MI; Nina D. Wagner-Johnston, Washington University School of Medicine, Saint Louis, MO; and Shaker Dakhil, Cancer Center of Kansas, Wichita, KS.
Lauren E
LE
Ta
Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Kathryn J. Ruddy, Nathan P. Staff, Axel Grothey, and Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Ellen M.L. Smith, University of Michigan, Ann Arbor, MI; Nina D. Wagner-Johnston, Washington University School of Medicine, Saint Louis, MO; and Shaker Dakhil, Cancer Center of Kansas, Wichita, KS.
Jacqueline M
JM
Lafky
Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Kathryn J. Ruddy, Nathan P. Staff, Axel Grothey, and Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Ellen M.L. Smith, University of Michigan, Ann Arbor, MI; Nina D. Wagner-Johnston, Washington University School of Medicine, Saint Louis, MO; and Shaker Dakhil, Cancer Center of Kansas, Wichita, KS.
Nina D
ND
Wagner-Johnston
Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Kathryn J. Ruddy, Nathan P. Staff, Axel Grothey, and Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Ellen M.L. Smith, University of Michigan, Ann Arbor, MI; Nina D. Wagner-Johnston, Washington University School of Medicine, Saint Louis, MO; and Shaker Dakhil, Cancer Center of Kansas, Wichita, KS.
Kathryn J
KJ
Ruddy
Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Kathryn J. Ruddy, Nathan P. Staff, Axel Grothey, and Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Ellen M.L. Smith, University of Michigan, Ann Arbor, MI; Nina D. Wagner-Johnston, Washington University School of Medicine, Saint Louis, MO; and Shaker Dakhil, Cancer Center of Kansas, Wichita, KS.
Shaker
S
Dakhil
Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Kathryn J. Ruddy, Nathan P. Staff, Axel Grothey, and Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Ellen M.L. Smith, University of Michigan, Ann Arbor, MI; Nina D. Wagner-Johnston, Washington University School of Medicine, Saint Louis, MO; and Shaker Dakhil, Cancer Center of Kansas, Wichita, KS.
Nathan P
NP
Staff
Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Kathryn J. Ruddy, Nathan P. Staff, Axel Grothey, and Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Ellen M.L. Smith, University of Michigan, Ann Arbor, MI; Nina D. Wagner-Johnston, Washington University School of Medicine, Saint Louis, MO; and Shaker Dakhil, Cancer Center of Kansas, Wichita, KS.
Axel
A
Grothey
Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Kathryn J. Ruddy, Nathan P. Staff, Axel Grothey, and Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Ellen M.L. Smith, University of Michigan, Ann Arbor, MI; Nina D. Wagner-Johnston, Washington University School of Medicine, Saint Louis, MO; and Shaker Dakhil, Cancer Center of Kansas, Wichita, KS.
Charles L
CL
Loprinzi
D000208:Acute Disease; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D017610:Calcium Compounds / Q000627:therapeutic use; D002908:Chronic Disease; D003110:Colonic Neoplasms / Q000188:drug therapy; D004311:Double-Blind Method; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D017616:Magnesium Compounds / Q000627:therapeutic use; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology* / Q000517:prevention & control; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology* / Q000517:prevention & control
D017610:Calcium Compounds; D017616:Magnesium Compounds; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil