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

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

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.

Study Overview

• Status: Completed
• Conditions: Peripheral Neuropathy; Breast Cancer Female
• Intervention / Treatment: Drug: Placebo; Drug: Pentoxifylline; Drug: Paclitaxel

Detailed Description

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
• Enrollment (Actual): 66
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Abbasia
    • Cairo, Abbasia, Egypt, 11566
      • Ain Shams University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum tumor necrosis factor alpha (TNF-α)	measuring serum level of tumor necrosis factor using ELISA kit	at baseline and after 12 weeks
Serum malondialdehyde (MDA)	measuring serum level of malondialdehyde.	at baseline and after 12 weeks
The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity(FACT-GOG-NTX) subscale	evaluating the functional difficulties and quality of life related to paclitaxel induced neuropathic symptoms. score range from (0-44) where lower score indicates more sever symptoms according to the FACT-GOG-NTX scoring guideline.	at baseline, week 1 in each cycle (cycle length is 21 days) up to 12 weeks and at week 12.
Time to develop neuropathy	mean time to develop grade 3 or 4 neuropathy	12 weeks

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2021
• Primary Completion (Actual): September 18, 2023
• Study Completion (Actual): September 28, 2023

Study Registration Dates

• First Submitted: October 4, 2021
• First Submitted That Met QC Criteria: January 8, 2022
• First Posted (Actual): January 12, 2022

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: paclitaxel; Breast cancer; peripheral neuropathy; Taxol; pentoxifylline; Trental
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neuromuscular Diseases; Breast Neoplasms; Peripheral Nervous System Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Paclitaxel; Pentoxifylline
• Other Study ID Numbers: s2192648

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No