Prevention of Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients

Study Overview
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Brief Summary
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The aim of this study is to evaluate the effect of pentoxifylline 400 mg twice daily administration on the prevention of paclitaxel-Induced peripheral neuropathy in breast cancer patients.

Detailed Description
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Paclitaxel induced peripheral neuropathy (PIPN) starts early during therapy and may worsen even after cessation and affect mainly sensory neurons. The symptoms of neuropathy include pain, tingling, cold-sensitivity and numbness that typically presents in a stocking glove distribution. The pathogenesis of PIPN may be attributed to drug accumulation in dorsal root ganglia causing increase in inflammatory cytokines, immune mediators and dysregulation of calcium subunits which in turn increases pain. It also causes oxidative stress in sensory axons leading to axon demyelination, increased sensitization to signal transduction, release of pro-inflammatory mediators and activation of apoptosis. Many animal studies and clinical trials have shown pentoxifylline to have a significant anti-inflammatory and antioxidant effect. It also preserved nerve conduction velocity and ameliorated mechanical hyperalgesia. Pentoxifylline showed a prominent reduction in neuropathic pain in diabetic patients. These effects were mainly due to the ability of pentoxifylline to reduce TNF-α and MDA levels. So, pentoxifylline is a drug of interest due to its ability to ameliorate neuro-inflammation and oxidative stress which play a critical role in PIPN pathogenesis.

Official Title
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Evaluation of the Effect of Pentoxifylline on the Prevention of Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients

Conditions
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Breast Cancer Female, Peripheral Neuropathy

Intervention / Treatment
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* Drug: Pentoxifylline
* Drug: Paclitaxel
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (18-80 years old). Female patients. Pathologically proved breast cancer. Breast cancer patients who will receive adjuvant and neoadjuvant weekly paclitaxel for 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance ≤ 2 Adequate bone marrow function. Adequate liver and kidney function. Exclusion Criteria: Patients with preexisting clinical neuropathy. Patients with diabetes mellitus. Metastatic breast cancer. Patients receiving medications that ameliorate neuropathy like; antidepressants, anticonvulsants, opioids, adjuvant or topical analgesics. Patients treated with medications that increase the risk of neuropathy. Hypersensitivity to pentoxifylline or xanthine derivatives. Patients with recent (within 1 month) surgery, myocardial infarction (MI), intracranial or retinal bleeding or active peptic ulcer. Patients at high risk for bleeding or taking medications that increase risk of bleeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A prospective, randomized, placebo controlled
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pentoxifylline 400 mg<br>Patients will receive paclitaxel 80 mg/m2 once per week for 12 weeks and pentoxifylline 400 mg twice daily for the paclitaxel treatment period. | Drug: Pentoxifylline<br>* Pentoxifylline 400 mg oral tablet twice daily for 12 weeks.<br>* Other names: Trental;Drug: Paclitaxel<br>* Paclitaxel I.V 80 mg/m2 weekly<br>* Other names: Taxol;|
| Placebo Comparator: Placebo<br>Patients will receive paclitaxel 80 mg/m2 once per week for 12 weeks and placebo twice daily for the paclitaxel treatment period.. | Drug: Paclitaxel<br>* Paclitaxel I.V 80 mg/m2 weekly<br>* Other names: Taxol;Drug: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Paclitaxel induced-peripheral neuropathy | Number of patients reported neuropathy due to paclitaxel | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade of severity of Paclitaxel induced-peripheral neuropathy in patients who developed neuropathy | Severity of neuropathic symptoms will be graded using Common Terminology Criteria for Adverse Events Version 5 (CTCAE v5) | at baseline and on weekly bases for 12 weeks | 
| Evaluation of Safety and tolerability of pentoxifylline | side effects reported due to pentoxifylline will be recorded. | evaluation on weekly bases for 12 weeks. | 
| The need for dose reduction or drug discontinuation in pentoxifylline and placebo arm. | number of patients who needed dose reduction or drug discontinuation due to paclitaxel induced neuropathy will be recorded. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, pentoxifylline, paclitaxel, Taxol, peripheral neuropathy, Trental