"Prevention of Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients"

Ain Shams University66 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Enrollment

Conditions

Breast Cancer Female Peripheral Neuropathy

Interventions

PentoxifyllineDRUG

Pentoxifylline 400 mg oral tablet twice daily for 12 weeks.

PaclitaxelDRUG

Paclitaxel I.V 80 mg/m2 weekly

PlaceboDRUG

placebo

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (1)

Ain Shams University hospitals

Cairo, Abbasia, Egypt

Outcomes

Primary Outcomes

Incidence of Paclitaxel induced-peripheral neuropathy

Number of patients reported neuropathy due to paclitaxel

Time frame: 12 weeks

Secondary Outcomes

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)

Time frame: 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.

Time frame: 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.

Time frame: 12 weeks

Data from ClinicalTrials.gov

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