Lidocaine Versus Duloxetine for the Prevention of Taxane-Induced Peripheral Neuropathy In Breast Cancer Patients
Condition: Peripheral Neuropathy; Chemotherapy-induced Peripheral Neuropathy; Breast Cancer
MeSH terms: Breast Neoplasms; Peripheral Nervous System Diseases
Study type: Interventional

Summary: 
      The aim of the study is to evaluate the effect of intravenous (IV) lidocaine versus oral
      duloxetine on the onset and severity of TIPN in patient with breast cancer as well as
      evaluation of Patients' quality of life and estimation the cell mediated immunity.

      The current study is a single blinded randomized controlled study, assumed that lidocaine
      could prevent and reduce TIPN similar to duloxetine in patient with breast cancer.

      Method of randomization: The allocation sequence was generated using permuted block
      randomization technique and the block size was variable. Allocation sequence/code was
      concealed from the person allocating the participants to the intervention arms using sealed
      opaque envelopes.

      Primary outcome: Degree of neuropathic pain measured by neuropathy pain scale (NPS) among
      breast cancer patients on Taxane chemotherapy after the pretreatment with either lidocaine or
      duloxetine.

      Secondary outcomes are: The incidence of TIPN using DN4 questionnaire and nerve conduction
      study and Patients' quality of life using The European Organization for Research and
      Treatment of Cancer (EORTC) QLQ-CIPN20 as well as the Change in serum level natural killer
      cell to estimate cell mediated immunity.
    

Detailed description: 
      Patients' assessment:

        -  Medical history (Previous diseases and medications)

        -  Clinical examination and laboratory investigations (according to patient' condition).

        -  Each patient will be informed with the study, its expected result and its possible side
           effects. The patients will be trained to use neuropathic pain scale (NPS). Additionally,
           DN4 questionnaire will be explained to all participants. IV line will be inserted for
           all participants. Vital signs including heart rate and mean arterial blood pressure will
           be measured.

      The participants will be randomly allocated into three groups as follows:

        -  Group control (C): 20 adult breast cancer patients on Taxane chemo protocol will receive
           200 ml normal saline over forty minutes pre each chemotherapy session until end of the
           cycle.

        -  Group lidocaine infusion (L): 20 adult breast cancer patients on Taxane chemo protocol
           will receive lidocaine IV infusion (2 mg/kg) in 200ml saline over forty minutes with a
           maximum upper limit of 200 mg pre each chemotherapy session until end of the cycle. If
           any selected patient reported neuropathic pain (DN4 > 4) during the course of
           chemotherapy lidocaine (2 mg/kg) re-infused after each session. If lidocaine side
           effects such as circumoral numbness, twitches, metal test, tachy or bradycardia recorded
           at any time, lidocaine infusion will be reduced to 1mg/kg, if side effects persist, the
           patients will be managed accordingly as well as lidocaine infusion will be stopped and
           patient will be excluded from the study.

        -  Group duloxetine (D): 20 adult breast cancer patients on chemotherapy will take oral
           duloxetine tablet 30 mg once per day starting from the night pre chemotherapy session
           until the end of cycle. If any selected patient reported neuropathic pain (DN4 > 4)
           during the course of chemotherapy the duloxetine dose will be adjusted to 60 mg daily
           till the end of the cycle. They also will receive 200 ml normal saline over forty
           minutes before each chemotherapy session until end of the cycle.

      Measurements

      Demographic features of the patients

      -Age (years), Weight (kg).

      Neuropathic pain characters and severity

      -Intensity and characters of neuropathic pain will be measured by neuropathic pain scale
      (0-10cm) after each chemotherapy session which is expected to be one session every week for
      12 weeks

      Chemotherapy induced peripheral neuropathy

        -  Nerve conduction study will be performed to detect sensory peripheral neuropathy pre and
           immediately after the end of chemo protocol cycle.

        -  Detection of TIPN will be measured using DN4 questionnaire before starting chemotherapy
           protocol and after each chemotherapy session which is expected to be one session every
           week for 12 weeks

      Patients' quality of life -The European Organization for Research and Treatment of Cancer
      (EORTC) QLQ-CIPN20 questionnaire for quality of life will be taken from patient before
      starting chemotherapy protocol ,one month ,two month after the treatment and at the end of
      treatment .

      Cell mediated immunity: Natural killer cell isolation and cytotoxicity assay.

      -Sample of 1ml of patients' peripheral blood will be collected on EDTA for flow cytometry to
      enumerate for both cytotoxic lymphocytes population (NK cells, and cytotoxic lymphocytes
      (ctls)). CD 56 will be used as a market for NK cells while CD8 will be used as a marker for
      Ctls. Cytotoxic assay will be done by measuring the release of lactate dehydrogenase (LDH)
      from non-viable cells (Cytotoxicity Detection kit, 630117; Clontech laboratories, Mountain
      View, California) according to manufacturer's instructions. Then ratio of LDH released
      specifically from NK cells will be carried according to the result of flow cytometry . Blood
      Sample will be collected at the start and the end of chemo protocol cycle of breast cancer
      patients.

      Complications

      -Any complications will occur during or after the treatment with lidocaine or duloxetine will
      be reported and managed accordingly.
    

Intervention name(s): Lidocaine in Saline; Duloxetine 30 MG; Normal saline
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Lidocaine IV infusion (2 mg/kg) in 200 ml saline over forty minutes with a maximum upper limit of 200 mg pre each chemotherapy session until end of the cycle.; Oral Duloxetine tablet 30 mg once per day starting from the night pre chemotherapy during the whole period of chemotherapy cycle which expected to be three month; 200 ml normal saline over forty minutes pre each chemotherapy session until end of the cycle.
Other intervention name(s): L; D; C
Intervention MeSH terms: Lidocaine; Duloxetine Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Breast cancer; Chemotherapy; Lidocaine; Duloxetine; Taxane induced peripheral neuropathy (TIPN)