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The Possible Protective Role of Ketotifen Against Oxaliplatin Induced Peripheral Neuropathy

ABSTRACT: The aim of current study is to evaluate the possible protective role of Ketotifen against oxaliplatin-induced peripheral sensory neuropathy in patient with stage III colorectal cancer. This study will be a randomized placebo controlled parallel study.64 patients with colorectal cancer will be randomized to 2 groups: Group I (control group; n=32) which will receive 12 cycles of modified FOLFOX-6 regimen plus placebo tablets twice daily. Group II (ketotifen group; n=32) which will receive modified FOLFOX-6 regimen in addition to ketotifen 2 mg daily Blood sample collection and biochemical assessment: * Serum IL-6 as a marker of inflammation. * Serum superoxide dismutase (SOD) as a biomarker of oxidative stress. * Serum neurotensin as a biomarker for neuropathy. Assessment of oxaliplatin induced peripheral sensory neuropathy will be done through: * The implication of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 5, 2017) for grading of neuropathy at baseline and by the end of every two oxaliplatin cycles. * The use of Neurotoxicity- 12 item questionnaire score (Ntx-12) from the validated Functional Assessment of Cancer Therapy/Gynecologic Oncology Group "FACT/GOG-Ntx-12" at baseline and by the end of every two oxaliplatin cycles. * The assessment of the severity of neuropathic pain through brief pain inventory short form "BPI-SF" worst item. Severity of neuropathic pain will be assessed at baseline and by the end of every two oxaliplatin cycles.

DISEASE(S): Peripheral Nervous System Diseases,Neuropathy;peripheral

PROVIDER: 488 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Protective Effect of Pentoxifylline Against Chemotherapy Induced Toxicities in Patients With Colorectal Cancer

Project description:This study aims to: - Evaluate the possible protective effect of pentoxifylline against oxaliplatin induced peripheral neuropathy and chemotherapy induced mucositis in patients with stage II and stage III colorectal cancer. This study will be a randomized placebo controlled parallel study.48 patients with colorectal cancer will be randomized to 2 groups: Group I (control group; n=24) which will receive 12 cycles of FOLFOX-6 regimen plus placebo tablets twice daily. Group II (Pentoxiphylline group; n=24) which will receive FOLFOX-6 regimen in addition to pentoxifylline 400 mg twice daily. Blood sample collection and biochemical assessment: * Malondialdehyde (MDA) as oxidative stress marker (colorimetry). * Tumor necrosis factor alfa (TNF-α) as pro inflammatory marker (ELISA). * Neurotensin (NT) as a potential marker for neuropathic pain (ELISA). * Citrulline as a biomarker for mucositis (ELISA). Clinical assessment of oxaliplatin induced neuropathy will be done through: The assessment of the severity of neuropathic pain through "Brief Pain Inventory-Short Form" at baseline and by the end of every two chemotherapy cycles. The implication of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 5, 2017) for grading of neuropathy every 2 cycles. The use of Neurotoxicity- 12 item questionnaire score (Ntx-12) from the validated Functional Assessment of Cancer Therapy/Gynecologic Oncology Group at baseline and by the end of every two chemotherapy cycles). Mucositis will be assessed at baseline and by the end of every two chemotherapy cycles through the use of common terminology criteria for adverse events "CTCAE, version 5.00, 2017

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2018-06-11 | E-MTAB-6864 | biostudies-arrayexpress

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Role of Xaliproden on Recovery Rate From Severe Neuropathy in Patients Who Have Completed Adjuvant Chemotherapy With Oxaliplatin Based Regimens

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Project description:Oxaliplatin-induced neuropathic pain is a common dose-limiting side effect of cancer treatment but the underlying mechanisms are largely unknown. The neuropathic pain model was established by oxaliplatin intraperitoneal administration for five consecutive days. In the present study, we performed whole genome expression microarray analysis by using spinal dorsal horn from oxaliplatin-treated and vehicle-treated rats on day 10.

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Gene expression signatures of chemotherapy-induced neuropathy induced by vincristine

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2019-06-01 | GSE125001 | GEO

Gene expression signatures of chemotherapy-induced neuropathy induced by cisplatin and oxaliplatin

2019-06-01 | GSE125002 | GEO

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Project description:Chemotherapy induced peripheral neuropathy (CIPN) is a dose-limiting painful neuropathy that occurs commonly during cancer management, which often leads to the discontinuation of medication. Previous studies suggest that the α9α10 nicotinic acetylcholine receptor (nAChR) specific antagonist αO-conotoxin GeXIVA[1,2] is effective in CIPN models, however the related mechanisms remains unclear. Here we analyzed the preventive effect of GeXIVA[1,2] on neuropathic pain in the long-term oxaliplatin injection induced CIPN model. At the end of treatment, lumbar (L4-L6) spinal cord was extracted, and RNA-sequencing and bioinformatic analysis were performed to investigate the potential genes and pathways related to CIPN and GeXIVA[1,2]. GeXIVA[1,2] inhibited the development of mechanical allodynia induced by chronic oxaliplatin treatment. Repeated injections of GeXIVA[1,2] for 3 weeks have no effect on mice normal pain threshold or locomotor activity and anxiety-like behavior as evaluated in the open field test (OFT) and elevated plus maze (EPM). Our RNA-sequencing results identified 209 differentially expressed genes (DEGs) in CIPN model, simultaneously injection of GeXIVA[1,2] with oxaliplatin altered 53 of the identified DEGs. These reverted genes were significantly enriched in immune-related pathways represented by cytokine-cytokine receptor interaction pathway. Our findings suggest that GeXIVA[1,2] could be a potential therapeutic compound for chronic oxaliplatin induced CIPN management.

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