Effect of Topical Diclofenac on Clinical Outcome in Breast Cancer Patients Treated With Capecitabine
Condition: Hand and Foot Syndrome
MeSH terms: Hand-Foot Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      The aim of the study is to evaluate the efficacy of using combination of Urea-based cream
      (CARBAMIDE®) and topical diclofenac (VOLTAREN®) Emulgel 1% for improving the incidence of
      Hand-foot syndrome in histologically proven breast cancer Egyptian patients receiving single
      agent chemotherapy Capecitabine (XELODA ®) and Its effect on improving patients' quality of
      life.
    

Detailed description: 
      Breast cancer (BC) is the most common cancer in women and the leading cause of death
      associated with cancer in females worldwide. BC, like most cancers, is a heterogeneous
      disease with a variety of molecular subtypes. Basal-like, Luminal-A, Luminal-B,
      HER2-positive/HER2-enriched/HER2-overexpressing BC, and normal-like tumors are the major
      subclasses identified by genetic profiling. Depending on the size, stage, grade, metastatic
      behavior, aggressiveness and intrinsic molecular subtyping of the tumor, age, menopausal
      status, overall health, comorbidities, and preferences of the patient, clinicians now have
      numerous options for breast cancer treatment. Treatment options include chemotherapy, hormone
      therapy, immunotherapy, radiotherapy, and surgery. The primary treatment option is usually
      surgery with the goal of complete resection of the major tumor mass. Surgery may be preceded
      by systemic neoadjuvant therapies to shrink the tumor in preparation for effective surgery
      and to maximize breast conservation.

      The United States FDA has approved a number of drugs for breast cancer therapy, including
      Capecitabine (Xeloda). However, these drugs are very pricey and have numerous side effects.
      Patients frequently report decreased appetite, dehydration, diarrhea, Hand-foot syndrome
      (HFS), irregular periods, mouth and throat sores, nausea, and vomiting as side effects of
      Capecitabine. These side effects are difficult for patients who are already weakened by the
      disease to tolerate. Eventually these also affect the decision for further choice of
      treatment and impair the quality of life. This necessitates the development of novel drugs
      for the treatment of breast cancer and This is the role of drug repurposing.

      The drug repositioning (aka drug repurposing, drug reprofiling, drug re-tasking, drug
      redesigning, drug resorting, drug reindication, indication switching, therapeutic switching)
      can be defined as exploring the new uses for an old clinically approved drug, with reduced
      risk, time and cost. Methotrexate, Raloxifene and Vinblastine are examples of Drug
      repurposing in breast cancer.

      Hand-foot syndrome (HFS) also Known as palmoplantar erythrodysesthesia, is a common side
      effect of the fluoropyrimidine chemotherapy drug capecitabine. According to reports, 43 % to
      71 %of patients receiving single-agent capecitabine chemotherapy have hand-foot syndrome of
      any grade.

      It is characterized initially by palmoplantar numbness, tingling, or burning pain. These
      symptoms are usually accompanied by clearly defined erythema with or without edema, cracking,
      or desquamation. Blistering and ulceration may occur in the advanced stages. HFS may manifest
      as macular hyperpigmentation rather than erythema in people with darker skin (Fitzpatrick
      skin types V-VI). Symptoms can range from mildly to severely painful.

      The pathogenesis of HFS is unclear, but it is assumed to be different for each drug class HFS
      causes a variety of toxic skin damage, ranging from non-specific scattered keratinocyte
      necrosis with basal vacuolar degeneration to full epidermal layer necrosis and (sub)epidermal
      blistering. In addition to eccrine squamous syringometaplasia, inflammation at the
      dermo-epidermal junction with papillary dermal edema, blood vessel dilation, and a
      lymphocytic infiltrate has been reported. The unique physiology of the palms and soles may
      clarify why the effects of these drugs are concentrated in these areas. The palms and soles
      are highly vascular, with higher rates of skin cell division than other skin areas, as well
      as high concentrations of eccrine glands and unique temperature modulation.

      Unfortunately, no specific guidelines exist for HFS, and only a few randomized trials
      demonstrating the benefit of topical treatments are available. The most effective way to
      manage HFS once it has developed is to modify dose intensity in the form of a dose delay or
      dose reduction, which will affect patients' treatment outcomes and quality of life such as
      daily activities like walking or using of hands.

      The treatment of choice for symptomatic HFS is determined by the severity of symptoms and
      their impact on Quality of Life (QoL). Vitamin E, steroids (oral dexamethasone), and
      analgesics are among the systemic treatment options. Current topical treatments are
      corticosteroids and emollients such as urea-based creams.

      Capecitabine and its metabolites are thought to cause COX-2-mediated inflammation; COX-2
      inhibition has been shown to be effective in the prevention of HFS. Topical non-steroidal
      anti-inflammatory inhibitors (NSAIDs), such as diclofenac, can inhibit COX-2 locally and may
      have a role in reducing HFS, without systemic side effects. However, no study has been
      conducted to date evaluating the role of topical COX inhibitors in reducing
      capecitabine-induced HFS. Hence, this study aimed to evaluate the efficacy and safety of
      topical diclofenac in reducing capecitabine-induced HFS.
    

Intervention name(s): (CARBAMIDE®); (VOLTAREN®) Emulgel 1%
Intervention type(s): Drug; Drug
Intervention description(s): Urea is used to treat dry/rough skin conditions (such as eczema, psoriasis, corns, callus) and some nail problems (such as ingrown nails). It may also be used to help remove dead tissue in some wounds to help wound healing. Urea is known as a keratolytic. It increases moisture in the skin by softening/dissolving the horny substance (keratin) holding the top layer of skin cells together. This effect helps the dead skin cells fall off and helps the skin keep more water in.; (VOLTAREN®) Emulgel 1% contain the active ingredient diclofenac which belongs to the NSAIDS.it has analgesic and anti-inflammatory properties and due to its alcohol base it has a cooling effect.
Other intervention name(s): Urea-based cream; Diclofenac Sodium
Intervention MeSH terms: Diclofenac
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study consists of 2 Arms, A control arm which will only receive standard of care (CARBAMIDE) and an intervention arm which will receive (CARBAMIDE and VOLTAREN)
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: Capecitabine; Breast Cancer; Hand and Foot Syndrome; Diclofenac Sodium