"The Effect of Memantine on the Prevention and Amelioration of Paclitaxel-induced Toxicity in Breast Cancer Patients"

Patients will be subjected to neurological examination every cycle to identify the presence and severity of PIPN. Grading of PIPN will be determined using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5 published in November 2017 (NCI, 2017). The NCI-CTCAE grades the adverse events based on their severity on a 5-point scale where "Grade 1" is defined as: Mild or asymptomatic symptoms requiring clinical or diagnostic observations only; Intervention not indicated. "Grade 2": Moderate symptoms limiting age-appropriate ADL; minimal, local or noninvasive intervention is indicated. "Grade 3": Severe symptoms or medically significant but not life-threatening that are disabling or limiting self-care in ADL; hospitalization or prolongation of hospitalization is indicated. "Grade 4": Life threatening consequences; urgent or emergent intervention is needed. "Grade 5": Death related to adverse event. The primary outcome will be the difference i

Pain severity will be quantified using the Brief Pain Inventory Short Form (BPI-SF) (Cleeland and Ryan, 1994). It is widely used in both research and clinical settings. Patients will be asked to rate their pain on a numerical scale every cycle. Each scale is presented as a row of equidistant numbers from zero to ten, where zero indicates "no pain" and ten indicates "pain as bad as you can imagine".

Patients' QoL will be assessed through The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity subscale (FACT/GOG-Ntx) questionnaire. The Ntx subscale is a reliable and valid instrument for assessing the impact of neuropathy on QoL that demonstrates sensitivity to meaningful clinical distinctions and change over time.

It is an eleven-item subscale that evaluates sensory neuropathy, motor neuropathy, hearing neuropathy, and dysfunction associated with CIPN for the previous 7 days. Each question in the Ntx subscale is represented by a Likert scale ranging from zero to four, where zero represents "not at all" and four represents "very much". The Ntx subscale generates a total score that is obtained by the summation of the composing question's scores. The total score ranges from 0 to 44 with higher scores indicating more severe neurotoxicity and worse QoL. The FACT/GOG-Ntx subscale will be evaluated at baseline, at 6 weeks, and 12 weeks.

Nerve growth factor, one of major neurotrophins, is known to regulate the growth, maintenance, and survival of neurons. Clinical evidence supports that depletion of NGF occurs during the development of CIPN. In cancer patients receiving taxanes, serum levels of NGF levels were shown to decrease after four to six cycles and decline was associated with the severity of PIPN. For the determination of serum levels of NGF, a blood sample of 4 ml will be collected from every patient.

The effect of memantine on depressive symptoms will be assessed through the nine-items Patient Health Questionnaire (PHQ-9). It is an easy-to-use self-administered questionnaire that reflects each of the nine criteria that the diagnosis of depression is based on according to the Diagnostic and Statistical Manual of Mental Disorders version V (DSM-V) criteria. The score for each question ranges from 0-3, as "0" (not at all) to "3" (nearly every day). The total score is obtained by adding up the individual items' scores. Scores range from 0 to 27 with scores from 0-4 indicating minimal depressive symptoms, 5-9: Mild, 10-14: Moderate, 15-19: Moderately severe, 20-27: Severe.