Clinical Course of Oxaliplatin-Induced Neuropathy: Results From the Randomized Phase III Trial N08CB (Alliance)

Pachman, Deirdre R.; Qin, Rui; Seisler, Drew K.; Smith, Ellen M. Lavoie; Beutler, Andreas S.; Ta, Lauren E.; Lafky, Jacqueline M.; Wagner‐Johnston, Nina D.; Ruddy, Kathryn J.; Dakhil, Shaker R.; Staff, Nathan P.; Grothey, Axel; Loprinzi, Charles L.

doi:10.1200/jco.2014.58.8533

Cited by 241 publications

(201 citation statements)

References 27 publications

(17 reference statements)

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“…We wrote a letter explaining the medical reasons for that so he could get his license. By the time, his peripheral neuropathy was fairly better especially in the hands, as expected [5].…”

Section: Klíčová Slovasupporting

confidence: 60%

Forbidden to Drive – a New Chemotherapy Side Effect

As²

2015

Klin Onkol

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SummaryBackground: Capecitabine is an oral antineoplastic agent classifi ed as a pyrimidin analogue. It is widely used in diff erent types of cancers. Unfortunately, it does not come without a cost, as the drug may have adverse eff ects -largely diarrhea, but also hand-foot syndrome and loss of fi ngerprints in extreme cases. Case: We report a case of a 47-year-old male, which had been dia gnosed with metastatic rectal cancer and received capecitabine, developing a severe hand foot syndrome which led him to lose his fi ngerprints in spite of complete resolution of the syndrome after stoppage of the drug. Conclusion: This case highlights a rare condition that, even though not precisely a disease per se, may hinder patient's quality of life and must be recognised by the treating physician as an treatment related side eff ect.

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“…We wrote a letter explaining the medical reasons for that so he could get his license. By the time, his peripheral neuropathy was fairly better especially in the hands, as expected [5].…”

Section: Klíčová Slovasupporting

confidence: 60%

Forbidden to Drive – a New Chemotherapy Side Effect

As²

2015

Klin Onkol

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“…Cold-related sensitivity is rated as the most severe symptom. Oxaliplatin-induced peripheral neuropathic pain in rats is a commonly used model of human chemotherapy-induced neuropathic pain (26). We therefore assessed the pain-relieving effects of RgIA4, which potently blocks α9α10 nAChRs but lacks activity on GABA B receptors.…”

Section: Resultsmentioning

confidence: 99%

“…It is an organoplatinum complex that is thought to produce cytotoxicity via the formation of DNA adducts that interfere with DNA replication and transcription, leading to the induction of apoptosis. Neurotoxicity is dosedependent, and symptoms (typically, increased sensitivity to cold) often continue to worsen for several months after completing chemotherapy, suggesting an ongoing disease process (26). There are currently no agents approved for prevention of the chemotherapy-induced peripheral neuropathy, often leaving clinicians to decrease the dose or duration of the medication treatment, thus diminishing the effectiveness of the intended cancer therapy (29).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of α9α10 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain

Romero

Christensen

Mannelli

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

141

204

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Opioids are first-line drugs for moderate to severe acute pain and cancer pain. However, these medications are associated with severe side effects, and whether they are efficacious in treatment of chronic nonmalignant pain remains controversial. Medications that act through alternative molecular mechanisms are critically needed. Antagonists of α9α10 nicotinic acetylcholine receptors (nAChRs) have been proposed as an important nonopioid mechanism based on studies demonstrating prevention of neuropathology after trauma-induced nerve injury. However, the key α9α10 ligands characterized to date are at least two orders of magnitude less potent on human vs. rodent nAChRs, limiting their translational application. Furthermore, an alternative proposal that these ligands achieve their beneficial effects by acting as agonists of GABA B receptors has caused confusion over whether blockade of α9α10 nAChRs is the fundamental underlying mechanism. To address these issues definitively, we developed RgIA4, a peptide that exhibits high potency for both human and rodent α9α10 nAChRs, and was at least 1,000-fold more selective for α9α10 nAChRs vs. all other molecular targets tested, including opioid and GABA B receptors. A daily s.c. dose of RgIA4 prevented chemotherapy-induced neuropathic pain in rats. In wild-type mice, oxaliplatin treatment produced cold allodynia that could be prevented by RgIA4. Additionally, in α9 KO mice, chemotherapy-induced development of cold allodynia was attenuated and the milder, temporary cold allodynia was not relieved by RgIA4. These findings establish blockade of α9-containing nAChRs as the basis for the efficacy of RgIA4, and that α9-containing nAChRs are a critical target for prevention of chronic cancer chemotherapyinduced neuropathic pain.pain | chemotherapy | alpha9 | nicotinic

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“…The acute phase, experienced by 85-95% of treated patients, is characterized by an increased sensitivity to touching cold items or swallowing cold liquids, throat discomfort, and muscle cramping. It is most pronounced 3 days after a given oxaliplatin infusion [3]. A chronic phase comprises sensory impairment of the distal peripheral nerves of the extremities.…”

Section: Introductionmentioning

confidence: 99%

A rat model of FOLFOX-induced neuropathy: effects of oral dimiracetam in comparison with duloxetine and pregabalin

Mannelli

Maresca

Micheli

et al. 2017

Cancer Chemother Pharmacol

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Results FOLFOX reduced the pain threshold in response to mechanical noxious and thermal (cold) non-noxious stimuli beginning from day 14 up to day 42 comparably to oxaliplatin alone. A fifth FOLFOX injection enhanced the severity but not the duration of painful alterations. Spontaneous activity, behavioural, autonomic, and neurological functions were also affected, whereas the motor coordination was not altered. On day 22, duloxetine (15 mg kg −1 , per os), morphine (10 mg kg −1 , subcutaneously), or pregabalin (20 mg kg −1 , per os), acutely administered, reduced the FOLFOX-dependent hypersensitivity. Repeated treatments with dimiracetam (150 mg kg −1 , per os, twice daily, from day 22) significantly protected rats from FOLFOX-induced alterations of pain threshold as well as from autonomic and neurological impairments taking effect after 7 days treatment. Pregabalin repeatedly administered (20 mg kg −1 , per os, twice daily, from day 22) was less effective in reducing mechanical hypersensitivity. Conclusion A clinically consistent model of FOL-FOX-induced neurotoxicity has been developed in rats. Dimiracetam fully reduced hypersensitivity and neurological alterations showing a relevant profile as anti-neuropathic resource.

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Clinical Course of Oxaliplatin-Induced Neuropathy: Results From the Randomized Phase III Trial N08CB (Alliance)

Abstract: 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.

Cited by 241 publications

References 27 publications

Forbidden to Drive – a New Chemotherapy Side Effect

Forbidden to Drive – a New Chemotherapy Side Effect

Inhibition of α9α10 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain

A rat model of FOLFOX-induced neuropathy: effects of oral dimiracetam in comparison with duloxetine and pregabalin

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