Effect of Topical Diclofenac on Clinical Outcome in Breast Cancer Patients Treated With Capecitabine

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.