Clinical trial NCT05189535: "Prevention of Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients"
Official title: "Evaluation of the Effect of Pentoxifylline on the Prevention of Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Breast Cancer Female
Peripheral Neuropathy
Keywords: Breast cancer
pentoxifylline
paclitaxel
Taxol
peripheral neuropathy
Trental
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2022-01-12
Enrollment: 66
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective, randomized, placebo controlled
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Paclitaxel induced-peripheral neuropathy
timeFrame: 12 weeks
Secondary outcomes:
measure: Grade of severity of Paclitaxel induced-peripheral neuropathy in patients who developed neuropathy
timeFrame: at baseline and on weekly bases for 12 weeks
measure: Evaluation of Safety and tolerability of pentoxifylline
timeFrame: evaluation on weekly bases for 12 weeks.
measure: The need for dose reduction or drug discontinuation in pentoxifylline and placebo arm.
timeFrame: 12 weeks
Other outcomes:
measure: Serum tumor necrosis factor alpha (TNF-α)
timeFrame: at baseline and after 12 weeks
measure: Serum malondialdehyde (MDA)
timeFrame: at baseline and after 12 weeks
measure: The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity(FACT-GOG-NTX) subscale
timeFrame: at baseline, week 1 in each cycle (cycle length is 21 days) up to 12 weeks and at week 12.
measure: Time to develop neuropathy
timeFrame: 12 weeks
Locations:
city: Cairo
country: Egypt
facility: Ain Shams University hospitals
state: Abbasia
Study officials:
References: