Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| pentoxifylline 400 mg | Experimental | Patients will receive paclitaxel 80 mg/m2 once per week for 12 weeks and pentoxifylline 400 mg twice daily for the paclitaxel treatment period. |
|
| Placebo | Placebo Comparator | Patients will receive paclitaxel 80 mg/m2 once per week for 12 weeks and placebo twice daily for the paclitaxel treatment period.. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pentoxifylline | Drug | Pentoxifylline 400 mg oral tablet twice daily for 12 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Paclitaxel induced-peripheral neuropathy | Number of patients reported neuropathy due to paclitaxel | 12 weeks |
| 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 |
| 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. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ain Shams University hospitals | Cairo | Abbasia | 11566 | Egypt |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D010523 | Peripheral Nervous System Diseases |
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D010431 | Pentoxifylline |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D013805 | Theobromine |
| D014970 | Xanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 |
Not provided
Not provided
A prospective, randomized, placebo controlled
Not provided
Not provided
single blinded
| Paclitaxel | Drug | Paclitaxel I.V 80 mg/m2 weekly |
|
|
| Placebo | Drug | placebo |
|
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 |
| 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 |
| D001941 |
| Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |