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

Ain Shams University

Status and phase: Completed; Phase 3; Phase 2

Conditions: Peripheral Neuropathy; Breast Cancer Female

Treatments: Drug: Paclitaxel; Drug: Placebo; Drug: Pentoxifylline

Study type: Interventional

Funder types: Other

Identifiers

NCT05189535

s2192648

Details and patient eligibility

About

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.

Full 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.

Enrollment: 66 patients

Sex: Female

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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66 participants in 2 patient groups, including a placebo group

pentoxifylline 400 mg

Experimental group

Description:

Patients will receive paclitaxel 80 mg/m2 once per week for 12 weeks and pentoxifylline 400 mg twice daily for the paclitaxel treatment period.

Treatment:

Drug: Pentoxifylline

Drug: Paclitaxel

Placebo

Placebo Comparator group

Description:

Patients will receive paclitaxel 80 mg/m2 once per week for 12 weeks and placebo twice daily for the paclitaxel treatment period..

Treatment:

Drug: Placebo

Drug: Paclitaxel